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Simple Summary Gliomas are heterogenous types of cancer, therefore the therapy should be personalized and targeted toward specific pathways. We developed a methodology that corrected strong batch effects from The Cancer Genome Atlas datasets and estimated glioma grade-specific co-enrichment mechanisms using machine learning. Our findings created hypotheses for annotations, e.g., pathways, that should be considered as therapeutic targets. Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment.
We present the discovery of a new double-detonation progenitor system consisting of a hot subdwarf B (sdB) binary with a white dwarf companion with a P (orb) = 76.34179(2) minutes orbital period. Spectroscopic observations are consistent with an sdB star during helium core burning residing on the extreme horizontal branch. Chimera light curves are dominated by ellipsoidal deformation of the sdB star and a weak eclipse of the companion white dwarf. Combining spectroscopic and light curve fits, we find a low-mass sdB star, M (sdB) = 0.383 +/- 0.028 M (circle dot) with a massive white dwarf companion, M (WD) = 0.725 +/- 0.026 M (circle dot). From the eclipses we find a blackbody temperature for the white dwarf of 26,800 K resulting in a cooling age of approximate to 25 Myr whereas our MESA model predicts an sdB age of approximate to 170 Myr. We conclude that the sdB formed first through stable mass transfer followed by a common envelope which led to the formation of the white dwarf companion approximate to 25 Myr ago. Using the MESA stellar evolutionary code we find that the sdB star will start mass transfer in approximate to 6 Myr and in approximate to 60 Myr the white dwarf will reach a total mass of 0.92 M (circle dot) with a thick helium layer of 0.17 M (circle dot). This will lead to a detonation that will likely destroy the white dwarf in a peculiar thermonuclear supernova. PTF1 J2238+7430 is only the second confirmed candidate for a double-detonation thermonuclear supernova. Using both systems we estimate that at least approximate to 1% of white dwarf thermonuclear supernovae originate from sdB+WD binaries with thick helium layers, consistent with the small number of observed peculiar thermonuclear explosions.
At the junction of greenhouse and icehouse climate states, the Eocene-Oligocene Transition (EOT) is a key moment in Cenozoic climate history. While it is associated with severe extinctions and biodiversity turnovers on land, the role of terrestrial climate evolution remains poorly resolved, especially the associated changes in seasonality. Some paleobotanical and geochemical continental records in parts of the Northern Hemisphere suggest the EOT is associated with a marked cooling in winter, leading to the development of more pronounced seasons (i.e., an increase in the mean annual range of temperature, MATR). However, the MATR increase has been barely studied by climate models and large uncertainties remain on its origin, geographical extent and impact. In order to better understand and describe temperature seasonality changes between the middle Eocene and the early Oligocene, we use the Earth system model IPSL-CM5A2 and a set of simulations reconstructing the EOT through three major climate forcings: pCO(2) decrease (1120, 840 and 560 ppm), the Antarctic ice-sheet (AIS) formation and the associated sea-level decrease. Our simulations suggest that pCO(2) lowering alone is not sufficient to explain the seasonality evolution described by the data through the EOT but rather that the combined effects of pCO(2) , AIS formation and increased continentality provide the best data-model agreement.pCO(2) decrease induces a zonal pattern with alternating increasing and decreasing seasonality bands particularly strong in the northern high latitudes (up to 8 degrees C MATR increase) due to sea-ice and surface albedo feedback. Conversely, the onset of the AIS is responsible for a more constant surface albedo yearly, which leads to a strong decrease in seasonality in the southern midlatitudes to high latitudes (> 40 degrees S). Finally, continental areas that emerged due to the sea-level lowering cause the largest increase in seasonality and explain most of the global heterogeneity in MATR changes (1MATR) patterns. The Delta MATR patterns we reconstruct are generally consistent with the variability of the EOT biotic crisis intensity across the Northern Hemisphere and provide insights on their underlying mechanisms.
Shams et al. report that glioma patients' motor status is predicted accurately by diffusion MRI metrics along the corticospinal tract based on support vector machine method, reaching an overall accuracy of 77%. They show that these metrics are more effective than demographic and clinical variables.
Along tract statistics enables white matter characterization using various diffusion MRI metrics. These diffusion models reveal detailed insights into white matter microstructural changes with development, pathology and function. Here, we aim at assessing the clinical utility of diffusion MRI metrics along the corticospinal tract, investigating whether motor glioma patients can be classified with respect to their motor status. We retrospectively included 116 brain tumour patients suffering from either left or right supratentorial, unilateral World Health Organization Grades II, III and IV gliomas with a mean age of 53.51 +/- 16.32 years. Around 37% of patients presented with preoperative motor function deficits according to the Medical Research Council scale. At group level comparison, the highest non-overlapping diffusion MRI differences were detected in the superior portion of the tracts' profiles. Fractional anisotropy and fibre density decrease, apparent diffusion coefficient axial diffusivity and radial diffusivity increase. To predict motor deficits, we developed a method based on a support vector machine using histogram-based features of diffusion MRI tract profiles (e.g. mean, standard deviation, kurtosis and skewness), following a recursive feature elimination method. Our model achieved high performance (74% sensitivity, 75% specificity, 74% overall accuracy and 77% area under the curve). We found that apparent diffusion coefficient, fractional anisotropy and radial diffusivity contributed more than other features to the model. Incorporating the patient demographics and clinical features such as age, tumour World Health Organization grade, tumour location, gender and resting motor threshold did not affect the model's performance, revealing that these features were not as effective as microstructural measures. These results shed light on the potential patterns of tumour-related microstructural white matter changes in the prediction of functional deficits.
Background:
Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making.
Methods:
127 subjects performed the two Step task and completed the blatant and subtle prejudice scale.
Results:
By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices.
Conclusion:
These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.
Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
Changes in snowpack associated with climatic warming has drastic impacts on surface energy balance in the cryosphere. Yet, traditional monitoring techniques, such as punctual measurements in the field, do not cover the full snowpack spatial and temporal variability, which hampers efforts to upscale measurements to the global scale. This variability is one of the primary constraints in model development. In terms of spatial resolution, active microwaves (synthetic aperture radar - SAR) can address the issue and outperform methods based on passive microwaves. Thus, high-spatial-resolution monitoring of snow depth (SD) would allow for better parameterization of local processes that drive the spatial variability of snow. The overall objective of this study is to evaluate the potential of the TerraSAR-X (TSX) SAR sensor and the wave co-polar phase difference (CPD) method for characterizing snow cover at high spatial resolution. Consequently, we first (1) investigate SD and depth hoar fraction (DHF) variability between different vegetation classes in the Ice Creek catchment (Qikiqtaruk/Herschel Island, Yukon, Canada) using in situ measurements collected over the course of a field campaign in 2019; (2) evaluate linkages between snow characteristics and CPD distribution over the 2019 dataset; and (3) determine CPD seasonality considering meteorological data over the 2015-2019 period. SD could be extracted using the CPD when certain conditions are met. A high incidence angle (>30 circle) with a high topographic wetness index (TWI) (>7.0) showed correlation between SD and CPD (R2 up to 0.72). Further, future work should address a threshold of sensitivity to TWI and incidence angle to map snow depth in such environments and assess the potential of using interpolation tools to fill in gaps in SD information on drier vegetation types.
IntroductionPostoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people. MethodsBetween November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD. ResultsPOD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher (OR = 2.74, 95% CI = 1.55-4.94) and 1.5-fold higher per additional point on the ARS (OR = 1.54, 95% CI = 1.15-2.02). ConclusionPreoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients.
Organic carbon (OC) stored in Arctic permafrost represents one of Earth's largest and most vulnerable terrestrial carbon pools. Amplified climate warming across the Arctic results in widespread permafrost thaw. Permafrost deposits exposed at river cliffs and coasts are particularly susceptible to thawing processes. Accelerating erosion of terrestrial permafrost along shorelines leads to increased transfer of organic matter (OM) to nearshore waters. However, the amount of terrestrial permafrost carbon and nitrogen as well as the OM quality in these deposits is still poorly quantified. We define the OM quality as the intrinsic potential for further transformation, decomposition and mineralisation. Here, we characterise the sources and the quality of OM supplied to the Lena River at a rapidly eroding permafrost river shoreline cliff in the eastern part of the delta (Sobo-Sise Island). Our multi-proxy approach captures bulk elemental, molecu- lar geochemical and carbon isotopic analyses of Late Pleistocene Yedoma permafrost and Holocene cover deposits, discontinuously spanning the last similar to 52 kyr. We showed that the ancient permafrost exposed in the Sobo-Sise cliff has a high organic carbon content (mean of about 5 wt %). The oldest sediments stem from Marine Isotope Stage (MIS) 3 interstadial deposits (dated to 52 to 28 cal ka BP) and are overlaid by last glacial MIS 2 (dated to 28 to 15 cal ka BP) and Holocene MIS 1 (dated to 7-0 cal ka BP) deposits. The relatively high average chain length (ACL) index of n-alkanes along the cliff profile indicates a predominant contribution of vascular plants to the OM composition. The elevated ratio of isoand anteiso-branched fatty acids (FAs) relative to mid- and long-chain (C >= 20) n-FAs in the interstadial MIS 3 and the interglacial MIS 1 deposits suggests stronger microbial activity and consequently higher input of bacterial biomass during these climatically warmer periods. The overall high carbon preference index (CPI) and higher plant fatty acid (HPFA) values as well as high C/N ratios point to a good quality of the preserved OM and thus to a high potential of the OM for decomposition upon thaw. A decrease in HPFA values downwards along the profile probably indicates stronger OM decomposition in the oldest (MIS 3) deposits of the cliff. The characterisation of OM from eroding permafrost leads to a better assessment of the greenhouse gas potential of the OC released into river and nearshore waters in the future.
The first step towards assessing hazards in seismically active regions involves mapping capable faults and estimating their recurrence times. While the mapping of active faults is commonly based on distinct geologic and geomorphic features evident at the surface, mapping blind seismogenic faults is complicated by the absence of on-fault diagnostic features. Here we investigated the Pichilemu Fault in coastal Chile, unknown until it generated a Mw 7.0 earthquake in 2010. The lack of evident surface faulting suggests activity along a partly-hidden blind fault. We used off-fault deformed marine terraces to estimate a fault-slip rate of 0.52 +/- 0.04 m/ka, which, when integrated with satellite geodesy suggests a 2.12 +/- 0.2 ka recurrence time for Mw similar to 7.0 normal-faulting earthquakes. We propose that extension in the Pichilemu region is associated with stress changes during megathrust earthquakes and accommodated by sporadic slip during upper-plate earthquakes, which has implications for assessing the seismic potential of cryptic faults along convergent margins and elsewhere.
Arctic river deltas and deltaic near-shore zones represent important land-ocean transition zones influencing sediment dynamics and nutrient fluxes from permafrost-affected terrestrial ecosystems into the coastal Arctic Ocean. To accurately model fluvial carbon and freshwater export from rapidly changing river catchments as well as assess impacts of future change on the Arctic shelf and coastal ecosystems, we need to understand the sea floor characteristics and topographic variety of the coastal zones. To date, digital bathymetrical data from the poorly accessible, shallow, and large areas of the eastern Siberian Arctic shelves are sparse. We have digitized bathymetrical information for nearly 75 000 locations from large-scale (1 V 25000-1 V 500000) current and historical nautical maps of the Lena Delta and the Kolyma Gulf region in northeastern Siberia. We present the first detailed and seamless digital models of coastal zone bathymetry for both delta and gulf regions in 50 and 200m spatial resolution. We validated the resulting bathymetry layers using a combination of our own water depth measurements and a collection of available depth measurements, which showed a strong correlation (r>0.9). Our bathymetrical models will serve as an input for a high-resolution coupled hydrodynamic-ecosystem model to better quantify fluvial and coastal carbon fluxes to the Arctic Ocean, but they may be useful for a range of other studies related to Arctic delta and near-shore dynamics such as modeling of submarine permafrost, near-shore sea ice, or shelf sediment transport. The new digital high-resolution bathymetry products are available on the PANGAEA data set repository for the Lena Delta (https://doi.org/10.1594/PANGAEA.934045; Fuchs et al., 2021a) and Kolyma Gulf region (https://doi.org/10.1594/PANGAEA.934049; Fuchs et al., 2021b), respectively. Likewise, the depth validation data are available on PANGAEA as well (https://doi.org/10.1594/PANGAEA.933187; Fuchs et al., 2021c).
Background/objective: Negative emotional states, such as depression, anxiety, and stress challenge health care due to their long-term consequences for mental disorders. Accumulating evidence indicates that regular physical activity (PA) can positively influence negative emotional states. Among possible candidates, resilience and exercise tolerance in particular have the potential to partly explain the positive effects of PA on negative emotional states. Thus, the aim of this study was to investigate the association between PA and negative emotional states, and further determine the mediating effects of exercise tolerance and resilience in such a relationship. Method: In total, 1117 Chinese college students (50.4% female, Mage=18.90, SD=1.25) completed a psychosocial battery, including the 21-item Depression Anxiety Stress Scale (DASS-21), the Connor-Davidson Resilience Scale (CD-RISC), the Preference for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q), and the International Physical Activity Questionnaire short form (IPAQ-SF). Regression analysis was used to identify the serial multiple mediation, controlling for gender, age and BMI. Results: PA, exercise intensity-tolerance, and resilience were significantly negatively correlated with negative emotional states (Ps<.05). Further, exercise tolerance and resilience partially mediated the relationship between PA and negative emotional states. Conclusions: Resilience and exercise intensity-tolerance can be achieved through regularly engaging in PA, and these newly observed variables play critical roles in prevention of mental illnesses, especially college students who face various challenges. Recommended amount of PA should be incorporated into curriculum or sport clubs within a campus environment.
Background/Objective: Historically, fasting has been practiced not only for medical but also for religious reasons. Baha'is follow an annual religious intermittent dry fast of 19 days. We inquired into motivation behind and subjective health impacts of Baha'i fasting. Methods: A convergent parallel mixed methods design was embedded in a clinical single arm observational study. Semi-structured individual interviews were conducted before (n = 7), during (n = 8), and after fasting (n = 8). Three months after the fasting period, two focus group interviews were conducted (n = 5/n = 3). A total of 146 Baha'i volunteers answered an online survey at five time points before, during, and after fasting. Results: Fasting was found to play a central role for the religiosity of interviewees, implying changes in daily structures, spending time alone, engaging in religious practices, and experiencing social belonging. Results show an increase in mindfulness and well-being, which were accompanied by behavioural changes and experiences of self-efficacy and inner freedom. Survey scores point to an increase in mindfulness and well-being during fasting, while stress, anxiety, and fatigue decreased. Mindfulness remained elevated even three months after the fast. Conclusion: Baha'i fasting seems to enhance participants' mindfulness and well-being, lowering stress levels and reducing fatigue. Some of these effects lasted more than three months after fasting.
Aging is one of the major non-reversible risk factors for several chronic diseases, including cancer, type 2 diabetes, dementia, and cardiovascular diseases (CVD), and it is a key cause of multimorbidity, disability, and frailty (decreased physical activity, fatigue, and weight loss). The underlying cellular mechanisms are complex and consist of multifactorial processes, such as telomere shortening, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, accumulation of senescent cells, and reduced autophagy. In this review, we focused on the molecular mechanisms and translational aspects of cardiovascular aging-related inflammation, i.e., inflammaging.
The Palaeocene-Eocene Thermal Maximum (ca. 56 million years ago) offers a primary analogue for future global warming and carbon cycle recovery. Yet, where and how massive carbon emissions were mitigated during this climate warming event remains largely unknown. Here we show that organic carbon burial in the vast epicontinental seaways that extended over Eurasia provided a major carbon sink during the Palaeocene-Eocene Thermal Maximum. We coupled new and existing stratigraphic analyses to a detailed paleogeographic framework and using spatiotemporal interpolation calculated ca. 720–1300 Gt organic carbon excess burial, focused in the eastern parts of the Eurasian epicontinental seaways. A much larger amount (2160–3900 Gt C, and when accounting for the increase in inundated shelf area 7400–10300 Gt C) could have been sequestered in similar environments globally. With the disappearance of most epicontinental seas since the Oligocene-Miocene, an effective negative carbon cycle feedback also disappeared making the modern carbon cycle critically dependent on the slower silicate weathering feedback.
An earthquake swarm affected the Bransfield Strait, Antarctica, a unique rift basin in transition from intra-arc rifting to ocean spreading. The swarm, counting similar to 85,000 volcano-tectonic earthquakes since August 2020, is located close to the Orca submarine volcano, previously considered inactive. Simultaneously, geodetic data reported up to similar to 11 cm north-westward displacement over King George Island. We use a broad variety of geophysical data and methods to reveal the complex migration of seismicity, accompanying the intrusion of 0.26-0.56 km(3) of magma. Strike-slip earthquakes mark the intrusion at depth, while shallower normal faulting the similar to 20 km long lateral growth of a dike. Seismicity abruptly decreased after a Mw 6.0 earthquake, suggesting the magmatic dike lost pressure with the slipping of a large fault. A seafloor eruption is likely, but not confirmed by sea surface temperature anomalies. The unrest documents episodic magmatic intrusion in the Bransfield Strait, providing unique insights into active continental rifting.
Recently, there has been an upsurge of activity in image-based non-photorealistic rendering (NPR), and in particular portrait image stylisation, due to the advent of neural style transfer (NST). However, the state of performance evaluation in this field is poor, especially compared to the norms in the computer vision and machine learning communities. Unfortunately, the task of evaluating image stylisation is thus far not well defined, since it involves subjective, perceptual, and aesthetic aspects. To make progress towards a solution, this paper proposes a new structured, three-level, benchmark dataset for the evaluation of stylised portrait images. Rigorous criteria were used for its construction, and its consistency was validated by user studies. Moreover, a new methodology has been developed for evaluating portrait stylisation algorithms, which makes use of the different benchmark levels as well as annotations provided by user studies regarding the characteristics of the faces. We perform evaluation for a wide variety of image stylisation methods (both portrait-specific and general purpose, and also both traditional NPR approaches and NST) using the new benchmark dataset.
In search of Ovidian hebrew
(2022)
This paper focuses on the first substantial translation of Ovid’s Metamorphoses into modern Hebrew, whose author was Yehoshua Friedman (1885–1934). The first part of the paper sets Friedman into the context of modern Hebrew classical philology and explores the character of his verse. The core of the text consists of three case studies of selected excerpts from Ovid’s story of Apollo and Daphne (Met. I, 456–465; 481–482; 545–552). Based on detailed linguistic and stylistic analysis of these texts, I argue that Friedman did not simply adopt a pre-existing linguistic register, but rather created an original Ovidian idiom that helped to win him lasting significance in the history of Hebrew translations from classical languages.
Solid organ transplant (SOT) recipients receive therapeutic immunosuppression that compromises their immune response to infections and vaccines. For this reason, SOT patients have a high risk of developing severe coronavirus disease 2019 (COVID-19) and an increased risk of death from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Moreover, the efficiency of immunotherapies and vaccines is reduced due to the constant immunosuppression in this patient group. Here, we propose adoptive transfer of SARS-CoV-2-specific T cells made resistant to a common immunosuppressant, tacrolimus, for optimized performance in the immunosuppressed patient. Using a ribonucleoprotein approach of CRISPR-Cas9 technology, we have generated tacrolimus-resistant SARS-CoV-2-specific T cell products from convalescent donors and demonstrate their specificity and function through characterizations at the single-cell level, including flow cytometry, single-cell RNA (scRNA) Cellular Indexing of Transcriptomes and Epitopes (CITE), and T cell receptor (TCR) sequencing analyses. Based on the promising results, we aim for clinical validation of this approach in transplant recipients. Additionally, we propose a combinatory approach with tacrolimus, to prevent an overshooting immune response manifested as bystander T cell activation in the setting of severe COVID-19 immunopathology, and tacrolimus-resistant SARS-CoV-2-specific T cell products, allowing for efficient clearance of viral infection. Our strategy has the potential to prevent severe COVID-19 courses in SOT or autoimmunity settings and to prevent immunopathology while providing viral clearance in severe non-transplant COVID-19 cases.
Background and aims: Accurate and user-friendly assessment tools quantifying alcohol consumption are a prerequisite to effective prevention and treatment programmes, including Screening and Brief Intervention. Digital tools offer new potential in this field. We developed the ‘Animated Alcohol Assessment Tool’ (AAA-Tool), a mobile app providing an interactive version of the World Health Organization's Alcohol Use Disorders Identification Test (AUDIT) that facilitates the description of individual alcohol consumption via culturally informed animation features. This pilot study evaluated the Russia-specific version of the Animated Alcohol Assessment Tool with regard to (1) its usability and acceptability in a primary healthcare setting, (2) the plausibility of its alcohol consumption assessment results and (3) the adequacy of its Russia-specific vessel and beverage selection. Methods: Convenience samples of 55 patients (47% female) and 15 healthcare practitioners (80% female) in 2 Russian primary healthcare facilities self-administered the Animated Alcohol Assessment Tool and rated their experience on the Mobile Application Rating Scale – User Version. Usage data was automatically collected during app usage, and additional feedback on regional content was elicited in semi-structured interviews. Results: On average, patients completed the Animated Alcohol Assessment Tool in 6:38 min (SD = 2.49, range = 3.00–17.16). User satisfaction was good, with all subscale Mobile Application Rating Scale – User Version scores averaging >3 out of 5 points. A majority of patients (53%) and practitioners (93%) would recommend the tool to ‘many people’ or ‘everyone’. Assessed alcohol consumption was plausible, with a low number (14%) of logically impossible entries. Most patients reported the Animated Alcohol Assessment Tool to reflect all vessels (78%) and all beverages (71%) they typically used. Conclusion: High acceptability ratings by patients and healthcare practitioners, acceptable completion time, plausible alcohol usage assessment results and perceived adequacy of region-specific content underline the Animated Alcohol Assessment Tool's potential to provide a novel approach to alcohol assessment in primary healthcare. After its validation, the Animated Alcohol Assessment Tool might contribute to reducing alcohol-related harm by facilitating Screening and Brief Intervention implementation in Russia and beyond.
All plant cells are encased in primary cell walls that determine plant morphology, but also protect the cells against the environment. Certain cells also produce a secondary wall that supports mechanically demanding processes, such as maintaining plant body stature and water transport inside plants. Both these walls are primarily composed of polysaccharides that are arranged in certain patterns to support cell functions. A key requisite for patterned cell walls is the arrangement of cortical microtubules that may direct the delivery of wall polymers and/or cell wall producing enzymes to certain plasma membrane locations. Microtubules also steer the synthesis of cellulose-the load-bearing structure in cell walls-at the plasma membrane. The organization and behaviour of the microtubule array are thus of fundamental importance to cell wall patterns. These aspects are controlled by the coordinated effort of small GTPases that probably coordinate a Turing's reaction-diffusion mechanism to drive microtubule patterns. Here, we give an overview on how wall patterns form in the water-transporting xylem vessels of plants. We discuss systems that have been used to dissect mechanisms that underpin the xylem wall patterns, emphasizing the VND6 and VND7 inducible systems, and outline challenges that lay ahead in this field.
Quinoa (Chenopodium quinoa Willd.) is an herbaceous annual crop of the amaranth family (Amaranthaceae). It is increasingly cultivated for its nutritious grains, which are rich in protein and essential amino acids, lipids, and minerals. Quinoa exhibits a high tolerance towards various abiotic stresses including drought and salinity, which supports its agricultural cultivation under climate change conditions. The use of quinoa grains is compromised by anti-nutritional saponins, a terpenoid class of secondary metabolites deposited in the seed coat; their removal before consumption requires extensive washing, an economically and environmentally unfavorable process; or their accumulation can be reduced through breeding. In this study, we analyzed the seed metabolomes, including amino acids, fatty acids, and saponins, from 471 quinoa cultivars, including two related species, by liquid chromatography - mass spectrometry. Additionally, we determined a large number of agronomic traits including biomass, flowering time, and seed yield. The results revealed considerable diversity between genotypes and provide a knowledge base for future breeding or genome editing of quinoa.
IntroductionThe COVID-19 pandemic has huge influences on daily life and is not only associated with physical but also with major psychological impacts. Mental health problems and disorders are frequently present in elite paralympic athletes. Due to the pandemic situation, new stressors (e.g., loss of routine, financial insecurity) might act upon the athletes. Therefore, the assessment of mental health in athletes during the COVID-19 pandemic is important to identify prevalence of psychological problems and propose countermeasures. MethodsThe mental health of German paralympic athletes was longitudinally monitored (starting in May 2019). The athletes completed the Patient Health Questionnaire 4 (PHQ-4) on a weekly basis and reported a stress level, training hours, and training load. During the pandemic, 8 measurement time points (March 2020 to April 2021) were used to reflect the psychological health course of the athletes. In parallel, a convenience sample of the general population was questioned about their psychological distress, including the PHQ-4. To be included in the analysis, participants of both groups had to complete at least 4 measurement time points. Matching of the para-athletes and the general population sample was prioritized upon completion of the same measurement time points, gender, and age. ResultsSeventy-eight paralympic athletes (40 women, 38 men, age: 29.8 +/- 11.4 years) met the inclusion criteria. Seventy-eight matched pairs of the general population (40 women; 38 men; age: 30.5 +/- 10.9 years) were identified. The para-athletes had a significantly (p r <0.48) lower PHQ-4 value at each measurement time point compared to the matched control group. No significant age or sex differences were evident regarding the symptom burden. In para-athletes, no significant and a weak positive correlation was found between decreased training load and PHQ-4 values and a stress level, respectively. Reduced physical activity was significantly (p <0.0001) associated with higher PHQ-4 values in the general population sample. DiscussionLower PHQ-4 values were reported by the para-athletes compared to the general population sample. However, small sample sizes must be considered while interpreting the data. Nevertheless, adequate support for individuals suffering from severe psychopathological symptoms should be provided for para-athletes as well as for the general population.
In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.
ObjectiveA role for microRNAs is implicated in several biological and pathological processes. We investigated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on molecular markers of diabetic cardiomyopathy in rats. MethodsEighteen male Wistar rats (260 +/- 10 g; aged 8 weeks) with streptozotocin (STZ)-induced type 1 diabetes mellitus (55 mg/kg, IP) were randomly allocated to three groups: control, MICT, and HIIT. The two different training protocols were performed 5 days each week for 5 weeks. Cardiac performance (end-systolic and end-diastolic dimensions, ejection fraction), the expression of miR-206, HSP60, and markers of apoptosis (cleaved PARP and cytochrome C) were determined at the end of the exercise interventions. ResultsBoth exercise interventions (HIIT and MICT) decreased blood glucose levels and improved cardiac performance, with greater changes in the HIIT group (p < 0.001, eta(2): 0.909). While the expressions of miR-206 and apoptotic markers decreased in both training protocols (p < 0.001, eta(2): 0.967), HIIT caused greater reductions in apoptotic markers and produced a 20% greater reduction in miR-206 compared with the MICT protocol (p < 0.001). Furthermore, both training protocols enhanced the expression of HSP60 (p < 0.001, eta(2): 0.976), with a nearly 50% greater increase in the HIIT group compared with MICT. ConclusionsOur results indicate that both exercise protocols, HIIT and MICT, have the potential to reduce diabetic cardiomyopathy by modifying the expression of miR-206 and its downstream targets of apoptosis. It seems however that HIIT is even more effective than MICT to modulate these molecular markers.
Pre-exposing (priming) plants to mild, non-lethal elevated temperature improves their tolerance to a later higher-temperature stress (triggering stimulus), which is of great ecological importance. 'Thermomemory' is maintaining this tolerance for an extended period of time. NAM/ATAF1/2/ CUC2 (NAC) proteins are plant-specific transcription factors (TFs) that modulate responses to abiotic stresses, including heat stress (HS). Here, we investigated the potential role of NACs for thermomemory. We determined the expression of 104 Ara bidopsis NAC genes after priming and triggering heat stimuli, and found ATAF1 expression is strongly induced right after priming and declines below control levels thereafter during thermorecovery. Knockout mutants of ATAF1 show better thermomemory than wild type, revealing a negative regulatory role. Differential expression analyses of RNA-seq data from ATAF1 overexpressor, ataf1 mutant and wild-type plants after heat priming revealed five genes that might be priming-associated direct targets of ATAF1: AT2G31260 (ATG9), AT2G41640 (GT61), AT3G44990 (XTH31), AT4G27720 and AT3G23540. Based on co-expression analyses applied to the aforementioned RNA-seq profiles, we identified ANAC055 to be transcriptionally co-regulated with ATAF1. Like atafl, anac055 mutants show improved thermomemory, revealing a potential co-control of both NACTFs over thermomemory. Our data reveals a core importance of two NAC transcription factors, ATAF1 and ANAC055, for thermomemory.
The Kolumbo submarine volcano in the southern Aegean (Greece) is associated with repeated seismic unrest since at least two decades and the causes of this unrest are poorly understood. We present a ten-month long microseismicity data set for the period 2006-2007. The majority of earthquakes cluster in a cone-shaped portion of the crust below Kolumbo. The tip of this cone coincides with a low Vp-anomaly at 2-4 km depth, which is interpreted as a crustal melt reservoir. Our data set includes several earthquake swarms, of which we analyze the four with the highest events numbers in detail. Together the swarms form a zone of fracturing elongated in the SW-NE direction, parallel to major regional faults. All four swarms show a general upward migration of hypocenters and the cracking front propagates unusually fast, compared to swarms in other volcanic areas. We conclude that the swarm seismicity is most likely triggered by a combination of pore-pressure perturbations and the re-distribution of elastic stresses. Fluid pressure perturbations are induced likely by obstructions in the melt conduits in a rheologically strong layer between 6 and 9 km depth. We conclude that the zone of fractures below Kolumbo is exploited by melts ascending from the mantle and filling the crustal melt reservoir. Together with the recurring seismic unrest, our study suggests that a future eruption is probable and monitoring of the Kolumbo volcanic system is highly advisable.
PRI: Re-analysis of a public mass cytometry dataset reveals patterns of effective tumor treatments
(2022)
Recently, mass cytometry has enabled quantification of up to 50 parameters for millions of cells per sample. It remains a challenge to analyze such high-dimensional data to exploit the richness of the inherent information, even though many valuable new analysis tools have already been developed. We propose a novel algorithm "pattern recognition of immune cells (PRI)" to tackle these high-dimensional protein combinations in the data. PRI is a tool for the analysis and visualization of cytometry data based on a three or more-parametric binning approach, feature engineering of bin properties of multivariate cell data, and a pseudo-multiparametric visualization. Using a publicly available mass cytometry dataset, we proved that reproducible feature engineering and intuitive understanding of the generated bin plots are helpful hallmarks for re-analysis with PRI. In the CD4(+)T cell population analyzed, PRI revealed two bin-plot patterns (CD90/CD44/CD86 and CD90/CD44/CD27) and 20 bin plot features for threshold-independent classification of mice concerning ineffective and effective tumor treatment. In addition, PRI mapped cell subsets regarding co-expression of the proliferation marker Ki67 with two major transcription factors and further delineated a specific Th1 cell subset. All these results demonstrate the added insights that can be obtained using the non-cluster-based tool PRI for re-analyses of high-dimensional cytometric data.
Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy
(2022)
Imaging the charge flow in photoexcited molecules would provide key information on photophysical and photochemical processes. Here the authors demonstrate tracking in real time after photoexcitation the change in charge density at a specific site of 2-thiouracil using time-resolved X-ray photoelectron spectroscopy. The conversion of photon energy into other energetic forms in molecules is accompanied by charge moving on ultrafast timescales. We directly observe the charge motion at a specific site in an electronically excited molecule using time-resolved x-ray photoelectron spectroscopy (TR-XPS). We extend the concept of static chemical shift from conventional XPS by the excited-state chemical shift (ESCS), which is connected to the charge in the framework of a potential model. This allows us to invert TR-XPS spectra to the dynamic charge at a specific atom. We demonstrate the power of TR-XPS by using sulphur 2p-core-electron-emission probing to study the UV-excited dynamics of 2-thiouracil. The method allows us to discover that a major part of the population relaxes to the molecular ground state within 220-250 fs. In addition, a 250-fs oscillation, visible in the kinetic energy of the TR-XPS, reveals a coherent exchange of population among electronic states.
Wildfires play an essential role in the ecology of boreal forests.
In eastern Siberia, fire activity has been increasing in recent years, challenging the livelihoods of local communities. Intensifying fire regimes also increase disturbance pressure on the boreal forests, which currently protect the permafrost beneath from accelerated degradation.
However, long-term relationships between changes in fire regime and forest structure remain largely unknown.
We assess past fire-vegetation feedbacks using sedimentary proxy records from Lake Satagay, Central Yakutia, Siberia, covering the past c. 10,800 years.
Results from macroscopic and microscopic charcoal analyses indicate high amounts of burnt biomass during the Early Holocene, and that the present-day, low-severity surface fire regime has been in place since c. 4,500 years before present.
A pollen-based quantitative reconstruction of vegetation cover and a terrestrial plant record based on sedimentary ancient DNA metabarcoding suggest a pronounced shift in forest structure toward the Late Holocene.
Whereas the Early Holocene was characterized by postglacial open larch-birch woodlands, forest structure changed toward the modern, mixed larch-dominated closed-canopy forest during the Mid-Holocene.
We propose a potential relationship between open woodlands and high amounts of burnt biomass, as well as a mediating effect of dense larch forest on the climate-driven intensification of fire regimes.
Considering the anticipated increase in forest disturbances (droughts, insect invasions, and wildfires), higher tree mortality may force the modern state of the forest to shift toward an open woodland state comparable to the Early Holocene.
Such a shift in forest structure may result in a positive feedback on currently intensifying wildfires.
These new long-term data improve our understanding of millennial-scale fire regime changes and their relationships to changes of vegetation in Central Yakutia, where the local population is already being confronted with intensifying wildfire seasons.
We characterize finite-time thermodynamic processes of multidimensional quadratic overdamped systems.
Analytic expressions are provided for heat, work, and dissipation for any evolution of the system covariance matrix.
The Bures-Wasserstein metric between covariance matrices naturally emerges as the local quantifier of dissipation.
General principles of how to apply these geometric tools to identify optimal protocols are discussed.
Focusing on the relevant slow-driving limit, we show how these results can be used to analyze cases in which the experimental control over the system is partial.
Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome.
The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation, and several other crucial processes during hantavirus infection.
In this study, we generated fluorescently tagged N protein constructs derived from Puumalavirus (PUUV), the dominant hantavirus species in Central, Northern, and Eastern Europe.
We comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn.
We observed formation of large, fibrillar PUUV N protein aggregates, rapidly coalescing from early punctate and spike-like assemblies.
Moreover, we found significant spatial correlation of N with vimentin, actin, and P-bodies but not with microtubules. N constructs also co-localized with Gn and Gc albeit not as strongly as the glycoproteins associated with each other.
Finally, we assessed oligomerization of N constructs, observing efficient and concentration-dependent multimerization, with complexes comprising more than 10 individual proteins.
Through its magnetic activity, the Sun governs the conditions in Earth's vicinity, creating space weather events, which have drastic effects on our space- and ground-based technology.
One of the most important solar magnetic features creating the space weather is the solar wind that originates from the coronal holes (CHs).
The identification of the CHs on the Sun as one of the source regions of the solar wind is therefore crucial to achieve predictive capabilities.
In this study, we used an unsupervised machine-learning method, k-means, to pixel-wise cluster the passband images of the Sun taken by the Atmospheric Imaging Assembly on the Solar Dynamics Observatory in 171, 193, and 211 angstrom in different combinations.
Our results show that the pixel-wise k-means clustering together with systematic pre- and postprocessing steps provides compatible results with those from complex methods, such as convolutional neural networks.
More importantly, our study shows that there is a need for a CH database where a consensus about the CH boundaries is reached by observers independently.
This database then can be used as the "ground truth," when using a supervised method or just to evaluate the goodness of the models.
Brain activation during active balancing and its behavioral relevance in younger and older adults
(2022)
Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted.
Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear.
Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored.
More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device.
As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty.
We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions.
Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency.
We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance.
Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance.
Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed.
Assessing the risk of yield loss in African drought-affected regions is key to identify feasible solutions for stable crop production. Recent studies have demonstrated that Copula-based probabilistic methods are well suited for such assessment owing to reasonably inferring important properties in terms of exceedance probability and joint dependence of different characterization. However, insufficient attention has been given to quantifying the probability of yield loss and determining the contribution of climatic factors. This study applies the Copula theory to describe the dependence between drought and crop yield anomalies for rainfed maize, millet, and sorghum crops in sub-Saharan Africa (SSA). The environmental policy integrated climate model, calibrated with Food and Agriculture Organization country-level yield data, was used to simulate yields across SSA (1980-2012). The results showed that the severity of yield loss due to drought had a higher magnitude than the severity of drought itself. Sensitivity analysis to identify factors contributing to drought and high-temperature stresses for all crops showed that the amount of precipitation during vegetation and grain filling was the main driver of crop yield loss, and the effect of temperature was stronger for sorghum than for maize and millet. The results demonstrate the added value of probabilistic methods for drought-impact assessment. For future studies, we recommend looking into factors influencing drought and high-temperature stresses as individual/concurrent climatic extremes.
Modern pollen-vegetation-climate relationships underpin palaeovegetation and palaeoclimate reconstructions from fossil pollen records. East Siberia is an ideal area for investigating the relationships between modern pollen assemblages and near natural vegetation under cold continental climate conditions. Reliable pollen-based quantitative vegetation and climate reconstructions are still scarce due to the limited number of modern pollen datasets. Furthermore, differences in pollen representation of samples from lake sediments and soils are not well understood. Here, we present a new pollen dataset of 48 moss/soil and 24 lake surface-sediment samples collected in Chukotka and central Yakutia in East Siberia. The pollen-vegetation-climate relationships were investigated by ordination analyses. Generally, tundra and taiga vegetation types can be well distinguished in the surface pollen assemblages. Moss/soil and lake samples contain generally similar pollen assemblages as revealed by a Procrustes comparison with some exceptions. Overall, modern pollen assemblages reflect the temperature and precipitation gradients in the study areas as revealed by constrained ordination analysis. We estimate the relative pollen productivity (RPP) of major taxa and the relevant source area of pollen (RSAP) for moss/soil samples from Chukotka and central Yakutia using Extended R-Value (ERV) analysis. The RSAP of the tundra-forest transition area in Chukotka and taiga area in central Yakutia are ca. 1300 and 360 m, respectively. For Chukotka, RPPs relative to both Poaceae and Ericaceae were estimated while RPPs for central Yakutia were relative only to Ericaceae. Relative to Ericaceae (reference taxon, RPP = 1), Larix, Betula, Picea, and Pinus are overrepresented while Alnus, Cyperaceae, Poaceae, and Salix are underrepresented in the pollen spectra. Our estimates are in general agreement with previously published values and provide the basis for reliable quantitative reconstructions of East Siberian vegetation.
Uncertainty in climate change impact studies for irrigated maize cropping systems in southern Spain
(2022)
This study investigates the main drivers of uncertainties in simulated irrigated maize yield under historical conditions as well as scenarios of increased temperatures and altered irrigation water availability.
Using APSIM, MONICA, and SIMPLACE crop models, we quantified the relative contributions of three irrigation water allocation strategies, three sowing dates, and three maize cultivars to the uncertainty in simulated yields.
The water allocation strategies were derived from historical records of farmer's allocation patterns in drip-irrigation scheme of the Genil-Cabra region, Spain (2014-2017).
By considering combinations of allocation strategies, the adjusted R-2 values (showing the degree of agreement between simulated and observed yields) increased by 29% compared to unrealistic assumptions of considering only near optimal or deficit irrigation scheduling. The factor decomposition analysis based on historic climate showed that irrigation strategies was the main driver of uncertainty in simulated yields (66%).
However, under temperature increase scenarios, the contribution of crop model and cultivar choice to uncertainty in simulated yields were as important as irrigation strategy. This was partially due to different model structure in processes related to the temperature responses.
Our study calls for including information on irrigation strategies conducted by farmers to reduce the uncertainty in simulated yields at field scale.
A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component
(2022)
Beyond its role in cellular homeostasis, autophagy plays anti- and promicrobial roles in host-microbe interactions, both in animals and plants.
One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy.
Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination.
Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown.
Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection.
Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery.
Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense-related autophagy in plant-bacteria interactions.
Etmopteridae (lantern sharks) is the most species-rich family of sharks, comprising more than 50 species.
Many species are described from few individuals, and re-collection of specimens is often hindered by the remoteness of their sampling sites.
For taxonomic studies, comparative morphological analysis of type specimens housed in natural history collections has been the main source of evidence.
In contrast, DNA sequence information has rarely been used.
Most lantern shark collection specimens, including the types, were formalin fixed before long-term storage in ethanol solutions.
The DNA damage caused by both fixation and preservation of specimens has excluded these specimens from DNA sequence-based phylogenetic analyses so far.
However, recent advances in the field of ancient DNA have allowed recovery of wet-collection specimen DNA sequence data.
Here we analyse archival mitochondrial DNA sequences, obtained using ancient DNA approaches, of two wet-collection lantern shark paratype specimens, namely Etmopterus litvinovi and E. pycnolepis, for which the type series represent the only known individuals.
Target capture of mitochondrial markers from single-stranded DNA libraries allows for phylogenetic placement of both species.
Our results suggest synonymy of E. benchleyi with E. litvinovi but support the species status of E. pycnolepis. This revised taxonomy is helpful for future conservation and management efforts, as our results indicate a larger distribution range of E. litvinovi. This study further demonstrates the importance of wet-collection type specimens as genetic resource for taxonomic research.
Air chemistry is affected by the emission of biogenic volatile organic compounds (BVOCs), which originate from almost all plants in varying qualities and quantities. They also vary widely among different crops, an aspect that has been largely neglected in emission inventories. In particular, bioenergy-related species can emit mixtures of highly reactive compounds that have received little attention so far. For such species, long-term field observations of BVOC exchange from relevant crops covering different phenological phases are scarcely available. Therefore, we measured and modeled the emission of three prominent European bioenergy crops (maize, ryegrass, and oil-seed rape) for full rotations in north-eastern Germany. Using a proton transfer reaction-mass spectrometer combined with automatically moving large canopy chambers, we were able to quantify the characteristic seasonal BVOC flux dynamics of each crop species. The measured BVOC fluxes were used to parameterize and evaluate the BVOC emission module (JJv) of the physiology-oriented LandscapeDNDC model, which was enhanced to cover de novo emissions as well as those from plant storage pools. Parameters are defined for each compound individually. The model is used for simulating total compound-specific reactivity over several years and also to evaluate the importance of these emissions for air chemistry. We can demonstrate substantial differences between the investigated crops with oil-seed rape having 37-fold higher total annual emissions than maize. However, due to a higher chemical reactivity of the emitted blend in maize, potential impacts on atmospheric OH-chemistry are only 6-fold higher.
As the recent permafrost thawing of northern Asia proceeds due to anthropogenic climate change, precise and detailed palaeoecological records from past warm periods are essential to anticipate the extent of future permafrost variations. Here, based on the modern relationship between permafrost and vegetation (represented by pollen assemblages), we trained a Random Forest model using pollen and permafrost data and verified its reliability to reconstruct the history of permafrost in northern Asia during the Holocene. An early Holocene (12-8 cal ka BP) strong thawing trend, a middle-to-late Holocene (8-2 cal ka BP) relatively slow thawing trend, and a late Holocene freezing trend of permafrost in northern Asia are consistent with climatic proxies such as summer solar radiation and Northern Hemisphere temperature. The extensive distribution of permafrost in northern Asia inhibited the spread of evergreen coniferous trees during the early Holocene warming and might have decelerated the enhancement of the East Asian summer monsoon (EASM) by altering hydrological processes and albedo. Based on these findings, we suggest that studies of the EASM should consider more the state of permafrost and vegetation in northern Asia, which are often overlooked and may have a profound impact on climate change in this region.
Arctic coasts, which feature land-ocean transport of freshwater, sediments, and other terrestrial material, are impacted by climate change, including increased temperatures, melting glaciers, changes in precipitation and runoff.
These trends are assumed to affect productivity in fjordic estuaries.
However, the spatial extent and temporal variation of the freshwater-driven darkening of fjords remain unresolved.
The present study illustrates the spatio-temporal variability of suspended particulate matter (SPM) in the Adventfjorden estuary, Svalbard, using in-situ field campaigns and ocean colour remote sensing (OCRS) via high-resolution Sentinel-2 imagery.
To compute SPM concentration (C-SPMsat), a semi-analytical algorithm was regionally calibrated using local in-situ data, which improved the accuracy of satellite-derived SPM concentration by similar to 20% (MRD). Analysis of SPM concentration for two consecutive years (2019, 2020) revealed strong seasonality of SPM in Adventfjorden.
Highest estimated SPM concentrations and river plume extent (% of fjord with C-SPMsat > 30 mg L-1) occurred during June, July, and August.
Concurrently, we observed a strong relationship between river plume extent and average air temperature over the 24 h prior to the observation (R-2 = 0.69).
Considering predicted changes to environmental conditions in the Arctic region, this study highlights the importance of the rapidly changing environmental parameters and the significance of remote sensing in analysing fluxes in light attenuating particles, especially in the coastal Arctic Ocean.
We investigate whether the distribution of maximum seasonal streamflow is significantly affected by catchment or climate state of the season/month ahead. We fit the Generalized Extreme Value (GEV) distribution to extreme seasonal streamflow for around 600 stations across Europe by conditioning the GEV location and scale parameters on 14 indices, which represent the season-ahead climate or catchment state. The comparison of these climate-informed models with the classical GEV distribution, with time-constant parameters, suggests that there is a substantial potential for seasonal forecasting of flood probabilities. The potential varies between seasons and regions. Overall, the season-ahead catchment wetness shows the highest potential, although climate indices based on large-scale atmospheric circulation, sea surface temperature or sea ice concentration also show some skill for certain regions and seasons. Spatially coherent patterns and a substantial fraction of climate-informed models are promising signs towards early alerts to increase flood preparedness already a season ahead.
Rapidly evolving floods are rare but powerful drivers of landscape reorganisation that have severe and long-lasting impacts on both the functions of a landscape's subsystems and the affected society. The July 2021 flood that particularly hit several river catchments of the Eifel region in western Germany and Belgium was a drastic example. While media and scientists highlighted the meteorological and hydrological aspects of this flood, it was not just the rising water levels in the main valleys that posed a hazard, caused damage, and drove environmental reorganisation. Instead, the concurrent coupling of landscape elements and the wood, sediment, and debris carried by the fast-flowing water made this flood so devastating and difficult to predict. Because more intense floods are able to interact with more landscape components, they at times reveal rare non-linear feedbacks, which may be hidden during smaller events due to their high thresholds of initiation. Here, we briefly review the boundary conditions of the 14-15 July 2021 flood and discuss the emerging features that made this event different from previous floods. We identify hillslope processes, aspects of debris mobilisation, the legacy of sustained human land use, and emerging process connections and feedbacks as critical non-hydrological dimensions of the flood. With this landscape scale perspective, we develop requirements for improved future event anticipation, mitigation, and fundamental system understanding.
We perform numerical studies of a thermally driven, overdamped particle in a random quenched force field, known as the Sinai model. We compare the unbounded motion on an infinite 1-dimensional domain to the motion in bounded domains with reflecting boundaries and show that the unbounded motion is at every time close to the equilibrium state of a finite system of growing size. This is due to time scale separation: inside wells of the random potential, there is relatively fast equilibration, while the motion across major potential barriers is ultraslow. Quantities studied by us are the time dependent mean squared displacement, the time dependent mean energy of an ensemble of particles, and the time dependent entropy of the probability distribution. Using a very fast numerical algorithm, we can explore times up top 10(17) steps and thereby also study finite-time crossover phenomena.
Background: Adolescents and young adults (AYA) with a chronic medical condition show an increased risk for developing mental comorbidities compared to their healthy peers. Internet- and mobile-based cognitive behavioral therapy (iCBT) might be a low-threshold treatment to support affected AYA. In this randomized controlled pilot trial, the feasibility and potential efficacy of youthCOACH(CD), an iCBT targeting symptoms of anxiety and depression in AYA with chronic medical conditions, was evaluated. Methods: A total of 30 AYA (M-age 16.13; SD= 2.34; 73% female), aged 12-21 years either suffering from cystic fibrosis, juvenile idiopathic arthritis or type 1 diabetes, were randomly assigned to either a guided version of the iCBT youthCOACH(CD) (IC, n=15) or to a waitlist control group (CG, n=15), receiving an unguided version of the iCBT six months post-randomization. Participants of the IG and the CG were assessed before (t0), twelve weeks after (t1) and six months after (t2) randomization. Primary outcome was the feasibility of the iCBT. Different parameters of feasibility e.g. acceptance, client satisfaction or potential side effects were evaluated. First indications of the possible efficacy with regard to the primary efficacy outcome, the Patient Health Questionnaire Anxiety and Depression Scale, and further outcome variables were evaluated using linear regression models, adjusting for baseline values. Results: Regarding feasibility, intervention completion was 60%; intervention satisfaction (M = 25.42, SD = 5.85) and perceived therapeutic alliance (M = 2.83, SD = 1.25) were moderate and comparable to other iCBTs. No patterns emerged regarding subjective and objective negative side effects due to participation in youthCOACH(CD). Estimates of potential efficacy showed between group differences, with a potential medium-term benefit of youthCOACH(CD) (beta = -0.55, 95%Cl: -1.17; 0.07), but probably not short-term (beta = 0.20, 95%Cl: -0.47; 0.88). Conclusions: Our results point to the feasibility of youthCOACH(CD) and the implementation of a future definitive randomized controlled trial addressing its effectiveness and cost-effectiveness. Due to the small sample size, conclusions are premature, however, further strategies to foster treatment adherence should be considered.
The present study estimated diet-related greenhouse gas emissions (GHGE) and land use (LU) in a sample of adults, examined main dietary contributors of GHGE, and evaluated socio demographic, lifestyle, and wellbeing factors as potential determinants of high environmental impact. A cross-sectional design based on data collected from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (2010-2012) was used. Usual diet was assessed using food frequency questionnaires. Diet-related GHGE and LU were calculated using a European-average lifecycle analyses-food-item database (SHARP-ID). Information on potential determinants were collected using self-administered questionnaires. Men (n = 404) and women (n = 401) at an average age of 66.0 +/- 8.4 years were included. Dietary-related energy-adjusted GHGE in men was 6.6 +/- 0.9 and in women was 7.0 +/- 1.1 kg CO2 eq per 2000 kcal. LU in men was 7.8 +/- 1.2 and in women was 7.7 +/- 1.2 m(2)/year per 2000 kcal. Food groups contributing to most GHGE included dairy, meat and non-alcoholic beverages. Among women, being single, having a job, being a smoker and having higher BMI were characteristics associated with higher GHGE, whereas for men these included being married, longer sleeping duration and higher BMI. Further studies are warranted to provide insights into population-specific determinants of sustainable dietary choices.
The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1-5 x MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8-40 mg/L and 16-80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing.
How accurately can we retrieve irrigation timing and water amounts from (satellite) soil moisture?
(2022)
While ensuring food security worldwide, irrigation is altering the water cycle and generating numerous environmental side effects. As detailed knowledge about the timing and the amounts of water used for irrigation over large areas is still lacking, remotely sensed soil moisture has proved potential to fill this gap.
However, the spatial resolution and revisit time of current satellite products represent a major limitation to accurately estimating irrigation. This work aims to systematically quantify their impact on the retrieved irrigation information, hence assessing the value of satellite soil moisture for estimating irrigation timing and water amounts.
In a real-world experiment, we modeled soil moisture using actual irrigation and meteorological data, obtained from farmers and weather stations, respectively. Modeled soil moisture was compared against various remotely sensed products differing in terms of spatio-temporal resolution to test the hypothesis that high-resolution observations can disclose the irrigation signal from individual fields while coarse-scale satellite products cannot.
Then, in a synthetic experiment, we systematically investigated the effect of soil moisture spatial and temporal resolution on the accuracy of irrigation estimates. The analysis was further elaborated by considering different irrigation scenarios and by adding realistic amounts of random errors in the soil moisture time series.
We show that coarse-scale remotely sensed soil moisture products achieve higher correlations with rainfed simulations, while high-resolution satellite observations agree significantly better with irrigated simulations, suggesting that high-resolution satellite soil moisture can inform on field-scale (similar to 40 ha) irrigation. A thorough analysis of the synthetic dataset showed that satisfactory results, both in terms of detection (F-score > 0.8) and quantification (Pearson's correlation > 0.8), are found for noise-free soil moisture observations either with a temporal sampling up to 3 days or if at least one-third of the pixel covers the irrigated field(s).
However, irrigation water amounts are systematically underestimated for temporal samplings of more than one day, and decrease proportionally to the spatial resolution, i.e., coarsening the pixel size leads to larger irrigation underestimations.
Although lower spatial and temporal resolutions decrease the detection and quantification accuracies (e.g., R between 0.6 and 1 depending on the irrigation rate and spatio-temporal resolution), random errors in the soil moisture time series have a stronger negative impact (Pearson R always smaller than 0.85).
As expected, better performances are found for higher irrigation rates, i.e. when more water is supplied during an irrigation event. Despite the potentially large underestimations, our results suggest that high-resolution satellite soil moisture has the potential to track and quantify irrigation, especially over regions where large volumes of irrigation water are applied to the fields, and given that low errors affect the soil moisture observations.
In vitro transcribed (IVT)-mRNA has been accepted as a promising therapeutic modality. Advances in facile and rapid production technologies make IVT-mRNA an appealing alternative to protein- or virus-based medicines.
Robust expression levels, lack of genotoxicity, and their manageable immunogenicity benefit its clinical applicability.
We postulated that innate immune responses of therapeutically relevant human cells can be tailored or abrogated by combinations of 5'-end and internal IVT-mRNA modifications.
Using primary human macrophages as targets, our data show the particular importance of uridine modifications for IVT-mRNA performance.
Among five nucleotide modification schemes tested, 5-methoxy-uridine outperformed other modifications up to 4-fold increased transgene expression, triggering moderate proinflammatory and non-detectable antiviral responses.
Macrophage responses against IVT-mRNAs exhibiting high immunogenicity (e.g., pseudouridine) could be minimized upon HPLC purification. Conversely, 5'-end modifications had only modest effects on mRNA expression and immune responses.
Our results revealed how the uptake of chemically modified IVT-mRNA impacts human macrophages, responding with distinct patterns of innate immune responses concomitant with increased transient transgene expression.
We anticipate our findings are instrumental to predictively address specific cell responses required for a wide range of therapeutic applications from eliciting controlled immunogenicity in mRNA vaccines to, e.g., completely abrogating cell activation in protein replacement therapies.
Instrumental data show that the groundwater and lake levels in Northeast Germany have decreased over the past decades, and this process has accelerated over the past few years. In addition to global warming, the direct influence of humans on the local water balance is suspected to be the cause. Since the instrumental data usually go back only a few decades, little is known about the multidecadal to centennial-scale trend, which also takes long-term climate variation and the long-term influence by humans on the water balance into account. This study aims to quantitatively reconstruct the surface water areas in the Lower Havel Inner Delta and of adjacent Lake Gulpe in Brandenburg. The analysis includes the calculation of surface water areas from historical and modern maps from 1797 to 2020. The major finding is that surface water areas have decreased by approximately 30% since the pre-industrial period, with the decline being continuous. Our data show that the comprehensive measures in Lower Havel hydro-engineering correspond with groundwater lowering that started before recent global warming. Further, large-scale melioration measures with increasing water demands in the upstream wetlands beginning from the 1960s to the 1980s may have amplified the decline in downstream surface water areas.
The past three decades of policy process studies have seen the emergence of a clear intellectual lineage with regard to complexity. Implicitly or explicitly, scholars have employed complexity theory to examine the intricate dynamics of collective action in political contexts. However, the methodological counterparts to complexity theory, such as computational methods, are rarely used and, even if they are, they are often detached from established policy process theory. Building on a critical review of the application of complexity theory to policy process studies, we present and implement a baseline model of policy processes using the logic of coevolving networks. Our model suggests that an actor's influence depends on their environment and on exogenous events facilitating dialogue and consensus-building. Our results validate previous opinion dynamics models and generate novel patterns. Our discussion provides ground for further research and outlines the path for the field to achieve a computational turn.
Leptonic nonthermal emission from supernova remnants evolving in the circumstellar magnetic field
(2022)
The very-high-energy (VHE; E > 100 GeV) gamma-ray emission observed from a number of supernova remnants (SNRs) indicates particle acceleration to high energies at the shock of the remnants and a potentially significant contribution to Galactic cosmic rays. It is extremely difficult to determine whether protons (through hadronic interactions and subsequent pion decay) or electrons (through inverse Compton scattering on ambient photon fields) are responsible for this emission. For a successful diagnostic, a good understanding of the spatial and energy distribution of the underlying particle population is crucial. Most SNRs are created in core-collapse explosions and expand into the wind bubble of their progenitor stars. This circumstellar medium features a complex spatial distribution of gas and magnetic field which naturally strongly affects the resulting particle population. In this work, we conduct a detailed study of the spectro-spatial evolution of the electrons accelerated at the forward shock of core-collapse SNRs and their nonthermal radiation, using the RATPaC code that is designed for the time- and spatially dependent treatment of particle acceleration at SNR shocks. We focus on the impact of the spatially inhomogeneous magnetic field through the efficiency of diffusion and synchrotron cooling. It is demonstrated that the structure of the circumstellar magnetic field can leave strong signatures in the spectrum and morphology of the resulting nonthermal emission.
Magnetic reconnection is a multi-faceted process of energy conversion in astrophysical, space and laboratory plasmas that operates at microscopic scales but has macroscopic drivers and consequences.
Solar flares present a key laboratory for its study, leaving imprints of the microscopic physics in radiation spectra and allowing the macroscopic evolution to be imaged, yet a full observational characterization remains elusive.
Here we combine high resolution imaging and spectral observations of a confined solar flare at multiple wavelengths with data-constrained magnetohydrodynamic modeling to study the dynamics of the flare plasma from the current sheet to the plasmoid scale. The analysis suggests that the flare resulted from the interaction of a twisted magnetic flux rope surrounding a filament with nearby magnetic loops whose feet are anchored in chromospheric fibrils. Bright cusp-shaped structures represent the region around a reconnecting separator or quasi-separator (hyperbolic flux tube).
The fast reconnection, which is relevant for other astrophysical environments, revealed plasmoids in the current sheet and separatrices and associated unresolved turbulent motions.
Solar flares provide wide range of observational details about fundamental processes involved. Here, the authors show evidence for magnetic reconnection in a strong confined solar flare displaying all four reconnection flows with plasmoids in the current sheet and the separatrices.
With the advent of Nanotechnology, the use of nanomaterials in consumer products is increasing on a daily basis, due to which a deep understanding and proper investigation regarding their safety and risk assessment should be a major priority. To date, there is no investigation regarding the microrheological properties of nanomaterials (NMs) in biological media.
In our study, we utilized in silico models to select the suitable NMs based on their physicochemical properties such as solubility and lipophilicity. Then, we established a new method based on dynamic light scattering (DLS) microrheology to get the mean square displacement (MSD) and viscoelastic property of two model NMs that are dendrimers and cerium dioxide nanoparticles in Dulbecco's Modified Eagle Medium (DMEM) complete media at three different concentrations for both NMs. Subsequently, we established the cytotoxicological profiling using water-soluble tetrazolium salt-1 (WST-1) and a reactive oxygen species (ROS) assay.
To take one step forward, we further looked into the tight junction properties of the cells using immunostaining with Zonula occluden-1 (ZO-1) antibodies and found that the tight junction function or transepithelial resistance (TEER) was affected in response to the microrheology and cytotoxicity. The quantitative polymerase chain reaction (q-PCR) results in the gene expression of ZO-1 after the 24 h treatment with NPs further validates the findings of immunostaining results.
This new method that we established will be a reference point for other NM studies which are used in our day-to-day consumer products.
Obesity has been linked to lower concentrations of fat-soluble micronutrients and higher concentrations of oxidative stress markers as well as an altered metabolism of branched chain amino acids and phospholipids. In the context of morbid obesity, the aim of this study was to investigate whether and to which extent plasma status of micronutrients, amino acids, phospholipids and oxidative stress differs between morbidly obese (n = 23) and non-obese patients (n = 13). In addition to plasma, malondialdehyde, retinol, cholesterol and triglycerides were assessed in visceral and subcutaneous adipose tissue in both groups. Plasma gamma-tocopherol was significantly lower (p < 0.011) in the obese group while other fat-soluble micronutrients showed no statistically significant differences between both groups. Branched-chain amino acids (all p < 0.008) and lysine (p < 0.006) were significantly higher in morbidly obese patients compared to the control group. Malondialdehyde concentrations in both visceral (p < 0.016) and subcutaneous (p < 0.002) adipose tissue were significantly higher in the morbidly obese group while plasma markers of oxidative stress showed no significant differences between both groups. Significantly lower plasma concentrations of phosphatidylcholine, phosphatidylethanolamine, lyso-phosphatidylethanolamine (all p < 0.05) and their corresponding ether-linked analogs were observed, which were all reduced in obese participants compared to the control group. Pre-operative assessment of micronutrients in patients undergoing bariatric surgery is recommended for early identification of patients who might be at higher risk to develop a severe micronutrient deficiency post-surgery. Assessment of plasma BCAAs and phospholipids in obese patients might help to differentiate between metabolic healthy patients and those with metabolic disorders.
The simultaneous detection of gravitational waves and light from the binary neutron star merger GW170817 led to independent measurements of distance and redshift, providing a direct estimate of the Hubble constant H-0 that does not rely on a cosmic distance ladder, nor assumes a specific cosmological model.
By using gravitational waves as "standard sirens", this approach holds promise to arbitrate the existing tension between the H-0 value inferred from the cosmic microwave background and those obtained from local measurements.
However, the known degeneracy in the gravitational-wave analysis between distance and inclination of the source led to a H-0 value from GW170817 that was not precise enough to resolve the existing tension.
In this review, we summarize recent works exploiting the viewing-angle dependence of the electromagnetic signal, namely the associated short gamma-ray burst and kilonova, to constrain the system inclination and improve on H-0.
We outline the key ingredients of the different methods, summarize the results obtained in the aftermath of GW170817 and discuss the possible systematics introduced by each of these methods.
In the last years, electron density profile functions characterized by a linear dependence on the scale height showed good results when approximating the topside ionosphere. The performance above 800 km, however, is not yet well investigated.
This study investigates the capability of the semi-Epstein functions to represent electron density profiles from the peak height up to 20,000 km. Electron density observations recorded by the Van Allen Probes were used to resolve the scale height dependence in the plasmasphere.
It was found that the linear dependence of the scale height in the topside ionosphere cannot be directly used to extrapolate profiles above 800 km.
We find that the dependence of scale heights on altitude is quadratic in the plasmasphere. A statistical model of the scale heights is therefore proposed. After combining the topside ionosphere and plasmasphere by a unified model, we have obtained good estimations not only in the profile shapes, but also in the Total Electron Content magnitude and distributions when compared to actual measurements from 2013, 2014, 2016 and 2017.
Our investigation shows that Van Allen Probes can be merged to radio-occultation data to properly represent the upper ionosphere and plasmasphere by means of a semi-Epstein function.
Simple Summary Asian elephants (Elephas maximus) are considered endangered and their population is in continuous decline. Understanding their social interactions, health, and welfare status has been a topic of intense research in recent decades. Coagulation assessments have been underutilized in wildlife but can give valuable information on individual health. This study aims to increase the knowledge of the coagulation status in healthy Asian elephants from different backgrounds and age groups, using a fast point-of-care analyzer. This tool can be further used in either routine health check-ups performed by caretakers or in a clinical emergency, such as in cases of elephant endotheliotropic herpesvirus hemorrhagic disease outbreaks. We have also investigated the presence of genomic mutations in one coagulation factor-factor VII-where a disorder was previously reported in an Asian elephant. Hereby, we report new reference values for coagulation parameters, such as coagulation times and fibrinogen concentration of Asian elephants assessed in Thailand and in Europe, as well as several single point mutations found in the exons of Elephas maximus coagulation F7 gene. We found the point-of-care analyzer used in this study to be very practical and user friendly for a zoo and field environment and hope that this project will incentivize further coagulation studies in Asian elephants and in other wildlife species. The Asian elephant population is continuously declining due to several extrinsic reasons in their range countries, but also due to diseases in captive populations worldwide. One of these diseases, the elephant endotheliotropic herpesvirus (EEHV) hemorrhagic disease, is very impactful because it particularly affects Asian elephant calves. It is commonly fatal and presents as an acute and generalized hemorrhagic syndrome. Therefore, having reference values of coagulation parameters, and obtaining such values for diseased animals in a very short time, is of great importance. We analyzed prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen concentrations using a portable and fast point-of-care analyzer (VetScan Pro) in 127 Asian elephants from Thai camps and European captive herds. We found significantly different PT and aPTT coagulation times between elephants from the two regions, as well as clear differences in fibrinogen concentration. Nevertheless, these alterations were not expected to have biological or clinical implications. We have also sequenced the coagulation factor VII gene of 141 animals to assess the presence of a previously reported hereditary coagulation disorder in Asian elephants and to investigate the presence of other mutations. We did not find the previously reported mutation in our study population. Instead, we discovered the presence of several new single nucleotide polymorphisms, two of them being considered as deleterious by effect prediction software.
Several morphological and mitochondrial lineages of the alpine ringlet butterfly species Erebia pronoe have been described, indicating a complex phylogenetic structure. However, the existing data were insufficient and allow neither a reconstruction of the biogeographic history, nor an assessment of the genetic lineages. Therefore, we analysed mitochondrial (COI, NDI) and nuclear (EF1 alpha, RPS5) gene sequences and compared them with sequences from the sister species Erebia melas. Additionally, we combined this information with morphometric data of the male genitalia and the infection patterns with Wolbachia strains, based on a WSP analysis. We obtained a distinct phylogeographic structure within the E. pronoe-melas complex with eight well-distinguishable geographic groups, but also a remarkable mito-nuclear discordance. The mito-nuclear discordance in E. melas and E. pronoe glottis can be explained by different ages of Wolbachia infections with different Wolbachia strains, associated selective sweeps, and hybridisation inhibition. Additionally, we found indications for incipient speciation of E. pronoe glottis in the Pyrenees and a pronounced range dynamic within and among the other high mountain systems of Europe. Our results emphasize the importance of combined approaches in reconstructing biogeographic patterns and evaluating phylogeographic splits.
Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional "Risks and Benefits of a Vegan Diet" (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64-111) in comparison to omnivores (median 104 g/day, IQR 88-143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.
Coronary artery disease (CAD) is the leading cause of death worldwide.
Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence.
Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD (n = 192) and those without (n = 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood.
Thus, our study supports a role of increased EPA levels for cardioprotection.
Canada's RADARSAT missions improve the potential to study past flood events; however, existing tools to derive flood depths from this remote-sensing data do not correct for errors, leading to poor estimates.
To provide more accurate gridded depth estimates of historical flooding, a new tool is proposed that integrates Height Above Nearest Drainage and Cost Allocation algorithms. This tool is tested against two trusted, hydraulically derived, gridded depths of recent floods in Canada.
This validation shows the proposed tool outperforms existing tools and can provide more accurate estimates from minimal data without the need for complex physics-based models or expert judgement.
With improvements in remote-sensing data, the tool proposed here can provide flood researchers and emergency managers accurate depths in near-real time.
The determination of the spin state of iron-bearing compounds at high pressure and temperature is crucial for our understanding of chemical and physical properties of the deep Earth. Studies on the relationship between the coordination of iron and its electronic spin structure in iron-bearing oxides, silicates, carbonates, iron alloys, and other minerals found in the Earth's mantle and core are scarce because of the technical challenges to simultaneously probe the sample at high pressures and temperatures. We used the unique properties of a pulsed and highly brilliant x-ray free electron laser (XFEL) beam at the High Energy Density (HED) instrument of the European XFEL to x-ray heat and probe samples contained in a diamond anvil cell. We heated and probed with the same x-ray pulse train and simultaneously measured x-ray emission and x-ray diffraction of an FeCO3 sample at a pressure of 51 GPa with up to melting temperatures. We collected spin state sensitive Fe K beta(1,3) fluorescence spectra and detected the sample's structural changes via diffraction, observing the inverse volume collapse across the spin transition. During x-ray heating, the carbonate transforms into orthorhombic Fe4C3O12 and iron oxides. Incipient melting was also observed. This approach to collect information about the electronic state and structural changes from samples contained in a diamond anvil cell at melting temperatures and above will considerably improve our understanding of the structure and dynamics of planetary and exoplanetary interiors.
Characterization of binding interactions of SARS-CoV-2 spike protein and DNA-peptide nanostructures
(2022)
Binding interactions of the spike proteins of the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) to a peptide fragment derived from the human angiotensin converting enzyme 2 (hACE2) receptor are investigated.
The peptide is employed as capture moiety in enzyme linked immunosorbent assays (ELISA) and quantitative binding interaction measurements that are based on fluorescence proximity sensing (switchSENSE).
In both techniques, the peptide is presented on an oligovalent DNA nanostructure, in order to assess the impact of mono- versus trivalent binding modes.
As the analyte, the spike protein and several of its subunits are tested as well as inactivated SARS-CoV-2 and pseudo viruses. While binding of the peptide to the full-length spike protein can be observed, the subunits RBD and S1 do not exhibit binding in the employed concentrations.
Variations of the amino acid sequence of the recombinant full-length spike proteins furthermore influence binding behavior. The peptide was coupled to DNA nanostructures that form a geometric complement to the trimeric structure of the spike protein binding sites.
An increase in binding strength for trimeric peptide presentation compared to single peptide presentation could be generally observed in ELISA and was quantified in switchSENSE measurements. Binding to inactivated wild type viruses could be shown as well as qualitatively different binding behavior of the Alpha and Beta variants compared to the wild type virus strain in pseudo virus models.
Efforts have been made in the past to enhance building exposure models on a regional scale with increasing spatial resolutions by integrating different data sources. This work follows a similar path and focuses on the downscaling of the existing SARA exposure model that was proposed for the residential building stock of the communes of Valparaiso and Vina del Mar (Chile). Although this model allowed great progress in harmonising building classes and characterising their differential physical vulnerabilities, it is now outdated, and in any case, it is spatially aggregated over large administrative units. Hence, to more accurately consider the impact of future earthquakes on these cities, it is necessary to employ more reliable exposure models. For such a purpose, we propose updating this existing model through a Bayesian approach by integrating ancillary data that has been made increasingly available from Volunteering Geo-Information (VGI) activities. Its spatial representation is also optimised in higher resolution aggregation units that avoid the inconvenience of having incomplete building-by-building footprints. A worst-case earthquake scenario is presented to calculate direct economic losses and highlight the degree of uncertainty imposed by exposure models in comparison with other parameters used to generate the seismic ground motions within a sensitivity analysis. This example study shows the great potential of using increasingly available VGI to update worldwide building exposure models as well as its importance in scenario-based seismic risk assessment.
Assessment of climate change impact on discharge of the lakhmass catchment (Northwest Tunisia)
(2022)
The Mediterranean region is increasingly recognized as a climate change hotspot but is highly underrepresented in hydrological climate change studies. This study aims to investigate the climate change effects on the hydrology of Lakhmass catchment in Tunisia. Lakhmass catchment is a part of the Medium Valley of Medjerda in northwestern Tunisia that drains an area of 126 km(2). First, the Hydrologiska Byrans Vattenbalansavdelning light (HBV-light) model was calibrated and validated successfully at a daily time step to simulate discharge during the 1981-1986 period. The Nash Sutcliffe Efficiency and Percent bias (NSE, PBIAS) were (0.80, +2.0%) and (0.53, -9.5%) for calibration (September 1982-August 1984) and validation (September 1984-August 1986) periods, respectively. Second, HBV-light model was considered as a predictive tool to simulate discharge in a baseline period (1981-2009) and future projections using data (precipitation and temperature) from thirteen combinations of General Circulation Models (GCMs) and Regional Climatic Models (RCMs). We used two trajectories of Representative Concentration Pathways, RCP4.5 and RCP8.5, suggested by the Intergovernmental Panel on Climate Change (IPCC). Each RCP is divided into three projection periods: near-term (2010-2039), mid-term (2040-2069) and long-term (2070-2099). For both scenarios, a decrease in precipitation and discharge will be expected with an increase in air temperature and a reduction in precipitation with almost 5% for every +1 degrees C of global warming. By long-term (2070-2099) projection period, results suggested an increase in temperature with about 2.7 degrees C and 4 degrees C, and a decrease in precipitation of approximately 7.5% and 15% under RCP4.5 and RCP8.5, respectively. This will likely result in a reduction of discharge of 12.5% and 36.6% under RCP4.5 and RCP8.5, respectively. This situation calls for early climate change adaptation measures under a participatory approach, including multiple stakeholders and water users.
Fast-localized electron loss, resulting from interactions with electromagnetic ion cyclotron (EMIC) waves, can produce deepening minima in phase space density (PSD) radial profiles. Here, we perform a statistical analysis of local PSD minima to quantify how readily these are associated with radiation belt depletions. The statistics of PSD minima observed over a year are compared to the Versatile Electron Radiation Belts (VERB) simulations, both including and excluding EMIC waves. The observed minima distribution can only be achieved in the simulation including EMIC waves, indicating their importance in the dynamics of the radiation belts. By analyzing electron flux depletions in conjunction with the observed PSD minima, we show that, in the heart of the outer radiation belt (L* < 5), on average, 53% of multi-MeV electron depletions are associated with PSD minima, demonstrating that fast localized loss by interactions with EMIC waves are a common and crucial process for ultra-relativistic electron populations.
A comparative whole-genome approach identifies bacterial traits for marine microbial interactions
(2022)
Luca Zoccarato, Daniel Sher et al. leverage publicly available bacterial genomes from marine and other environments to examine traits underlying microbial interactions.
Their results provide a valuable resource to investigate clusters of functional and linked traits to better understand marine bacteria community assembly and dynamics.
Microbial interactions shape the structure and function of microbial communities with profound consequences for biogeochemical cycles and ecosystem health. Yet, most interaction mechanisms are studied only in model systems and their prevalence is unknown. To systematically explore the functional and interaction potential of sequenced marine bacteria, we developed a trait-based approach, and applied it to 473 complete genomes (248 genera), representing a substantial fraction of marine microbial communities.
We identified genome functional clusters (GFCs) which group bacterial taxa with common ecology and life history. Most GFCs revealed unique combinations of interaction traits, including the production of siderophores (10% of genomes), phytohormones (3-8%) and different B vitamins (57-70%). Specific GFCs, comprising Alpha- and Gammaproteobacteria, displayed more interaction traits than expected by chance, and are thus predicted to preferentially interact synergistically and/or antagonistically with bacteria and phytoplankton. Linked trait clusters (LTCs) identify traits that may have evolved to act together (e.g., secretion systems, nitrogen metabolism regulation and B vitamin transporters), providing testable hypotheses for complex mechanisms of microbial interactions.
Our approach translates multidimensional genomic information into an atlas of marine bacteria and their putative functions, relevant for understanding the fundamental rules that govern community assembly and dynamics.
The time instant-the first-passage time (FPT)-when a diffusive particle (e.g., a ligand such as oxygen or a signalling protein) for the first time reaches an immobile target located on the surface of a bounded three-dimensional domain (e.g., a hemoglobin molecule or the cellular nucleus) is a decisive characteristic time-scale in diverse biophysical and biochemical processes, as well as in intermediate stages of various inter- and intra-cellular signal transduction pathways. Adam and Delbruck put forth the reduction-of-dimensionality concept, according to which a ligand first binds non-specifically to any point of the surface on which the target is placed and then diffuses along this surface until it locates the target. In this work, we analyse the efficiency of such a scenario and confront it with the efficiency of a direct search process, in which the target is approached directly from the bulk and not aided by surface diffusion. We consider two situations: (i) a single ligand is launched from a fixed or a random position and searches for the target, and (ii) the case of 'amplified' signals when N ligands start either from the same point or from random positions, and the search terminates when the fastest of them arrives to the target. For such settings, we go beyond the conventional analyses, which compare only the mean values of the corresponding FPTs. Instead, we calculate the full probability density function of FPTs for both scenarios and study its integral characteristic-the 'survival' probability of a target up to time t. On this basis, we examine how the efficiencies of both scenarios are controlled by a variety of parameters and single out realistic conditions in which the reduction-of-dimensionality scenario outperforms the direct search.
Marine sedimentary archives are routinely used to reconstruct past environmental changes. In many cases, bioturbation and sedimentary mixing affect the proxy time-series and the age-depth relationship. While idealized models of bioturbation exist, they usually assume homogeneous mixing, thus that a single sample is representative for the sediment layer it is sampled from.
However, it is largely unknown to which extent this assumption holds for sediments used for paleoclimate reconstructions.
To shed light on
1) the age-depth relationship and its full uncertainty,
2) the magnitude of mixing processes affecting the downcore proxy variations, and
3) the representativity of the discrete sample for the sediment layer, we designed and performed a case study on South China Sea sediment material which was collected using a box corer and which covers the last glacial cycle.
Using the radiocarbon content of foraminiferal tests as a tracer of time, we characterize the spatial age-heterogeneity of sediments in a three-dimensional setup. In total, 118 radiocarbon measurements were performed on defined small- and large-volume bulk samples ( similar to 200 specimens each) to investigate the horizontal heterogeneity of the sediment. Additionally, replicated measurements on small numbers of specimens (10 x 5 specimens) were performed to assess the heterogeneity within a sample volume. Visual assessment of X-ray images and a quantitative assessment of the mixing strength show typical mixing from bioturbation corresponding to around 10 cm mixing depth.
Notably, our 3D radiocarbon distribution reveals that the horizontal heterogeneity (up to 1,250 years), contributing to the age uncertainty, is several times larger than the typically assumed radiocarbon based age-model error (single errors up to 250 years). Furthermore, the assumption of a perfectly bioturbated layer with no mixing underneath is not met.
Our analysis further demonstrates that the age-heterogeneity might be a function of sample size; smaller samples might contain single features from the incomplete mixing and are thus less representative than larger samples.
We provide suggestions for future studies, optimal sampling strategies for quantitative paleoclimate reconstructions and realistic uncertainty in age models, as well as discuss possible implications for the interpretation of paleoclimate records.
In this study we present a novel method for the automatic detection of minerals and elements using hyperspectral transmittance imaging microscopy measurements of complete thin sections (HyperTIM).
This is accomplished by using a hyperspectral camera system that operates in the visible and near-infrared (VNIR) range with a specifically designed sample holder, scanning setup, and a microscope lens.
We utilize this method on a monazite ore thin section from Steenkampskraal (South Africa), which we analyzed for the rare earth element (REE)-bearing mineral monazite ((Ce,Nd,La)PO4), with high concentrations of Nd. The transmittance analyses with the hyperspectral VNIR camera can be used to identify REE minerals and Nd in thin sections.
We propose a three-point band depth index, the Nd feature depth index (NdFD), and its related product the Nd band depth index (NdBDI), which enables automatic mineral detection and classification for the Nd-bearing monazites in thin sections. In combination with the average concentration of the relative Nd content, it permits a destruction-free, total concentration calculation for Nd across the entire thin section.
Background
Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes.
It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes.
We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops.
Methods
Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years).
Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression.
Results
In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints).
Conclusions
Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.
Food preferences are crucial for diet-related decisions, which substantially impact individual health and global climate. However, the persistence of unfavorable food preferences is a significant obstacle to changing eating behavior.
Here we explored the effects of posthypnotic suggestions (PHS) on food-related decisions by measuring food choices, subjective ratings, and indifference points. In Session 1, demographic data and hypnotic susceptibility of participants were assessed. In Session 2, following hypnosis induction, PHS aiming to increase the desirability of healthy food was delivered.
Afterward, a task set was administrated twice, once when PHS was activated and once deactivated. The order of PHS activation was counterbalanced across participants. The task set included a liking-rating task for 170 pictures of different food items, followed by an online supermarket where participants were instructed to select enough food for a fictitious week of quarantining from the same item pool. After 1 week, Session 3 repeated Session 2 without hypnosis induction in order to assess the persistence of PHS.
The crucial dependent measures were food choices, subjective ratings, and the indifference points as a function of time and PHS condition.
Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling.
Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations.
In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions.
In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.
LegacyPollen 1.0
(2022)
Here we describe the LegacyPollen 1.0, a dataset of 2831 fossil pollen records with metadata, a harmonized taxonomy, and standardized chronologies.
A total of 1032 records originate from North America, 1075 from Europe, 488 from Asia, 150 from Latin America, 54 from Africa, and 32 from the Indo-Pacific.
The pollen data cover the late Quaternary (mostly the Holocene). The original 10 110 pollen taxa names (including variations in the notations) were harmonized to 1002 terrestrial taxa (including Cyperaceae), with woody taxa and major herbaceous taxa harmonized to genus level and other herbaceous taxa to family level.
The dataset is valuable for synthesis studies of, for example, taxa areal changes, vegetation dynamics, human impacts (e.g., deforestation), and climate change at global or continental scales.
The harmonized pollen and metadata as well as the harmonization table are available from PANGAEA (https://doi.org/10.1594/PANGAEA.929773; Herzschuh et al., 2021). R code for the harmonization is provided at Zenodo (https://doi.org/10.5281/zenodo.5910972; Herzschuh et al., 2022) so that datasets at a customized harmonization level can be easily established.
Manganese (Mn) as well as iron (Fe) are essential trace elements (TE) important for the maintenance of physiological functions including fetal development. However, in the case of Mn, evidence suggests that excess levels of intrauterine Mn are associated with adverse pregnancy outcomes. Although Mn is known to cross the placenta, the fundamentals of Mn transfer kinetics and mechanisms are largely unknown. Moreover, exposure to combinations of TEs should be considered in mechanistic transfer studies, in particular for TEs expected to share similar transfer pathways. Here, we performed a mechanistic in vitro study on the placental transfer of Mn across a BeWo b30 trophoblast layer. Our data revealed distinct differences in the placental transfer of Mn and Fe. While placental permeability to Fe showed a clear inverse dose-dependency, Mn transfer was largely independent of the applied doses. Concurrent exposure of Mn and Fe revealed transfer interactions of Fe and Mn, indicating that they share common transfer mechanisms. In general, mRNA and protein expression of discussed transporters like DMT1, TfR, or FPN were only marginally altered in BeWo cells despite the different exposure scenarios highlighting that Mn transfer across the trophoblast layer likely involves a combination of active and passive transport processes.
Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described.
However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients.
Eleven myasthenia gravis patients (age: 70.64 +/- 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 +/- 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors.
Structural brain changes were determined by applying voxel-based morphometry using high-resolution T-1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels.
Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200).
Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions.
Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail.
Klaus et al. compared myasthenia gravis patients to matched healthy control subjects and identified functional alterations in memory functions as well as structural alterations in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus.
We argue for a perspective on bilingual heritage speakers as native speakers of both their languages and present results from a large-scale, cross-linguistic study that took such a perspective and approached bilinguals and monolinguals on equal grounds.
We targeted comparable language use in bilingual and monolingual speakers, crucially covering broader repertoires than just formal language. A main database was the open-access RUEG corpus, which covers comparable informal vs. formal and spoken vs. written productions by adolescent and adult bilinguals with heritage-Greek, -Russian, and -Turkish in Germany and the United States and with heritage-German in the United States, and matching data from monolinguals in Germany, the United States, Greece, Russia, and Turkey. Our main results lie in three areas.
(1) We found non-canonical patterns not only in bilingual, but also in monolingual speakers, including patterns that have so far been considered absent from native grammars, in domains of morphology, syntax, intonation, and pragmatics.
(2) We found a degree of lexical and morphosyntactic inter-speaker variability in monolinguals that was sometimes higher than that of bilinguals, further challenging the model of the streamlined native speaker.
(3) In majority language use, non-canonical patterns were dominant in spoken and/or informal registers, and this was true for monolinguals and bilinguals. In some cases, bilingual speakers were leading quantitatively. In heritage settings where the language was not part of formal schooling, we found tendencies of register leveling, presumably due to the fact that speakers had limited access to formal registers of the heritage language.
Our findings thus indicate possible quantitative differences and different register distributions rather than distinct grammatical patterns in bilingual and monolingual speakers. This supports the integration of heritage speakers into the native-speaker continuum. Approaching heritage speakers from this perspective helps us to better understand the empirical data and can shed light on language variation and change in native grammars.
Furthermore, our findings for monolinguals lead us to reconsider the state-of-the art on majority languages, given recurring evidence for non-canonical patterns that deviate from what has been assumed in the literature so far, and might have been attributed to bilingualism had we not included informal and spoken registers in monolinguals and bilinguals alike.
High annotation costs are a substantial bottleneck in applying deep learning architectures to clinically relevant use cases, substantiating the need for algorithms to learn from unlabeled data.
In this work, we propose employing self-supervised methods. To that end, we trained with three self-supervised algorithms on a large corpus of unlabeled dental images, which contained 38K bitewing radiographs (BWRs). We then applied the learned neural network representations on tooth-level dental caries classification, for which we utilized labels extracted from electronic health records (EHRs). Finally, a holdout test-set was established, which consisted of 343 BWRs and was annotated by three dental professionals and approved by a senior dentist.
This test-set was used to evaluate the fine-tuned caries classification models. Our experimental results demonstrate the obtained gains by pretraining models using self-supervised algorithms. These include improved caries classification performance (6 p.p. increase in sensitivity) and, most importantly, improved label-efficiency.
In other words, the resulting models can be fine-tuned using few labels (annotations).
Our results show that using as few as 18 annotations can produce >= 45% sensitivity, which is comparable to human-level diagnostic performance.
This study shows that self-supervision can provide gains in medical image analysis, particularly when obtaining labels is costly and expensive.
Stimulus data and experimental design for a self-paced reading study on emoji-word substitutions
(2022)
This data paper presents the experimental design and stimuli from an online self-paced reading study on the processing of emojis substituting lexically ambiguous nouns. We recorded reading times for the target ambiguous nouns and for emojis depicting either the intended target referent or a contextually inappropriate homophonous noun. Furthermore, we recorded comprehension accuracy, demographics and a self-assessment of the participants' emoji usage frequency. The data includes all stimuli used, the raw data, the full JavaScript code for the online experiment, as well as Python and R code for the data analysis. We believe that our dataset may give important insights related to the comprehension mechanisms involved in the cognitive processing of emojis. For interpretation and discussion of the experiment, please see the original article entitled "The processing of emoji-word substitutions: A self-paced-reading study".
Landslides in deglaciated and deglaciating mountains represent a major hazard, but their distribution at the spatial scale of entire mountain belts has rarely been studied. Traditional models of landslide distribution assume that landslides are concentrated in the steepest, wettest, and most tectonically active parts of the orogens, where glaciers reached their greatest thickness.
However, based on mapping large landslides (>0.9 km(2)) over an unprecedentedly large area of Southern Patagonia (similar to 305,000 km(2)), we show that the distribution of landslides can have the opposite trend.
We show that the largest landslides within the limits of the former Patagonian Ice Sheet (PIS) cluster along its eastern margins occupying lower, tectonically less active, and arid part of the Patagonian Andes. In contrast to the heavily glaciated, highest elevations of the mountain range, the peripheral regions have been glaciated only episodically, leaving a larger volume of unstable sedimentary and volcanic rocks that are subject to ongoing slope instability.
Incorporation of noncanonical amino acids (ncAAs) with bioorthogonal reactive groups by amber suppression allows the generation of synthetic proteins with desired novel properties. Such modified molecules are in high demand for basic research and therapeutic applications such as cancer treatment and in vivo imaging. The positioning of the ncAA-responsive codon within the protein's coding sequence is critical in order to maintain protein function, achieve high yields of ncAA-containing protein, and allow effective conjugation. Cell-free ncAA incorporation is of particular interest due to the open nature of cell-free systems and their concurrent ease of manipulation. In this study, we report a straightforward workflow to inquire ncAA positions in regard to incorporation efficiency and protein functionality in a Chinese hamster ovary (CHO) cell-free system. As a model, the well-established orthogonal translation components Escherichia coli tyrosyl-tRNA synthetase (TyrRS) and tRNATyr(CUA) were used to site-specifically incorporate the ncAA p-azido-l-phenylalanine (AzF) in response to UAG codons. A total of seven ncAA sites within an anti-epidermal growth factor receptor (EGFR) single-chain variable fragment (scFv) N-terminally fused to the red fluorescent protein mRFP1 and C-terminally fused to the green fluorescent protein sfGFP were investigated for ncAA incorporation efficiency and impact on antigen binding. The characterized cell-free dual fluorescence reporter system allows screening for ncAA incorporation sites with high incorporation efficiency that maintain protein activity. It is parallelizable, scalable, and easy to operate. We propose that the established CHO-based cell-free dual fluorescence reporter system can be of particular interest for the development of antibody-drug conjugates (ADCs).
We study the first-arrival (first-hitting) dynamics and efficiency of a one-dimensional random search model performing asymmetric Levy flights by leveraging the Fokker-Planck equation with a delta-sink and an asymmetric space-fractional derivative operator with stable index alpha and asymmetry (skewness) parameter beta.
We find exact analytical results for the probability density of first-arrival times and the search efficiency, and we analyse their behaviour within the limits of short and long times.
We find that when the starting point of the searcher is to the right of the target, random search by Brownian motion is more efficient than Levy flights with beta <= 0 (with a rightward bias) for short initial distances, while for beta>0 (with a leftward bias) Levy flights with alpha -> 1 are more efficient.
When increasing the initial distance of the searcher to the target, Levy flight search (except for alpha=1 with beta=0) is more efficient than the Brownian search. Moreover, the asymmetry in jumps leads to essentially higher efficiency of the Levy search compared to symmetric Levy flights at both short and long distances, and the effect is more pronounced for stable indices alpha close to unity.
Soil bacteria play a fundamental role in pedogenesis. However, knowledge about both the impact of climate and slope aspects on microbial communities and the consequences of these items in pedogenesis is lacking. Therefore, soil-bacterial communities from four sites and two different aspects along the climate gradient of the Chilean Coastal Cordillera were investigated. Using a combination of microbiological and physicochemical methods, soils that developed in arid, semi-arid, mediterranean, and humid climates were analyzed. Proteobacteria, Acidobacteria, Chloroflexi, Verrucomicrobia, and Planctomycetes were found to increase in abundance from arid to humid climates, while Actinobacteria and Gemmatimonadetes decreased along the transect. Bacterial-community structure varied with climate and aspect and was influenced by pH, bulk density, plant-available phosphorus, clay, and total organic-matter content. Higher bacterial specialization was found in arid and humid climates and on the south-facing slope and was likely promoted by stable microclimatic conditions. The presence of specialists was associated with ecosystem-functional traits, which shifted from pioneers that accumulated organic matter in arid climates to organic decomposers in humid climates. These findings provide new perspectives on how climate and slope aspects influence the composition and functional capabilities of bacteria, with most of these capabilities being involved in pedogenetic processes.
Genomic prediction has revolutionized crop breeding despite remaining issues of transferability of models to unseen environmental conditions and environments. Usage of endophenotypes rather than genomic markers leads to the possibility of building phenomic prediction models that can account, in part, for this challenge. Here, we compare and contrast genomic prediction and phenomic prediction models for 3 growth-related traits, namely, leaf count, tree height, and trunk diameter, from 2 coffee 3-way hybrid populations exposed to a series of treatment-inducing environmental conditions. The models are based on 7 different statistical methods built with genomic markers and ChlF data used as predictors. This comparative analysis demonstrates that the best-performing phenomic prediction models show higher predictability than the best genomic prediction models for the considered traits and environments in the vast majority of comparisons within 3-way hybrid populations. In addition, we show that phenomic prediction models are transferrable between conditions but to a lower extent between populations and we conclude that chlorophyll a fluorescence data can serve as alternative predictors in statistical models of coffee hybrid performance. Future directions will explore their combination with other endophenotypes to further improve the prediction of growth-related traits for crops.
Reducing greenhouse gas emissions in food systems is becoming more challenging as food is increasingly consumed away from producer regions, highlighting the need to consider emissions embodied in trade in agricultural emissions accounting.
To address this, our study explores recent trends in trade-adjusted agricultural emissions of food items at the global, regional, and national levels.
We find that emissions are largely dependent on a country’s consumption patterns and their agricultural emission intensities relative to their trading partners’.
The absolute differences between the production-based and trade-adjusted emissions accounting approaches are especially apparent for major agricultural exporters and importers and where large shares of emission-intensive items such as ruminant meat, milk products and rice are involved.
In relative terms, some low-income and emerging and developing economies with consumption of high emission intensity food products show large differences between approaches.
Similar trends are also found under various specifications that account for trade and re-exports differently.
These findings could serve as an important element towards constructing national emissions reduction targets that consider trading partners, leading to more effective emissions reductions overall.
The Lena Delta in Siberia is the largest delta in the Arctic and as a snow-dominated ecosystem particularly vulnerable to climate change.
Using the two decades of MODerate resolution Imaging Spectroradiometer satellite acquisitions, this study investigates interannual and spatial variability of snow-cover duration and summer vegetation vitality in the Lena Delta.
We approximated snow by the application of the normalized difference snow index and vegetation greenness by the normalized difference vegetation index (NDVI). We consolidated the analyses by integrating reanalysis products on air temperature from 2001 to 2021, and air temperature, ground temperature, and the date of snow-melt from time-lapse camera (TLC) observations from the Samoylov observatory located in the central delta.
We extracted spring snow-cover duration determined by a latitudinal gradient. The 'regular year' snow-melt is transgressing from mid-May to late May within a time window of 10 days across the delta.
We calculated yearly deviations per grid cell for two defined regions, one for the delta, and one focusing on the central delta. We identified an ensemble of early snow-melt years from 2012 to 2014, with snow-melt already starting in early May, and two late snow-melt years in 2004 and 2017, with snow-melt starting in June. In the times of TLC recording, the years of early and late snow-melt were confirmed.
In the three summers after early snow-melt, summer vegetation greenness showed neither positive nor negative deviations. Whereas, vegetation greenness was reduced in 2004 after late snow-melt together with the lowest June monthly air temperature of the time series record. Since 2005, vegetation greenness is rising, with maxima in 2018 and 2021.
The NDVI rise since 2018 is preceded by up to 4 degrees C warmer than average June air temperature. The ongoing operation of satellite missions allows to monitor a wide range of land surface properties and processes that will provide urgently needed data in times when logistical challenges lead to data gaps in land-based observations in the rapidly changing Arctic.
The concepts of CO2 emission, global warming, climate change, and their environmental impacts are of utmost importance for the understanding and protection of the ecosystems.
Among the natural sources of gases into the atmosphere, the contribution of geogenic sources plays a crucial role. However, while subaerial emissions are widely studied, submarine outgassing is not yet well understood.
In this study, we review and catalog 122 literature and unpublished data of submarine emissions distributed in ten coastal areas of the Aegean Sea. This catalog includes descriptions of the degassing vents through in situ observations, their chemical and isotopic compositions, and flux estimations.
Temperatures and pH data of surface seawaters in four areas affected by submarine degassing are also presented.
This overview provides useful information to researchers studying the impact of enhanced seawater CO2 concentrations related either to increasing CO2 levels in the atmosphere or leaking carbon capture and storage systems.
The production of volatile organic compounds (VOCs) represents a promising strategy of plant-beneficial bacteria to control soil-borne phytopathogens.
Pseudomonas sp. PICF6 and Pseudomonas simiae PICF7 are two indigenous inhabitants of olive roots displaying effective biological control against Verticillium dahliae. Additionally, strain PICF7 is able to promote the growth of barley and Arabidopsis thaliana, VOCs being involved in the growth of the latter species.
In this study, the antagonistic capacity of these endophytic bacteria against relevant phytopathogens (Verticillium spp., Rhizoctonia solani, Sclerotinia sclerotiorum and Fusarium oxysporum f.sp. lycopersici) was assessed. Under in vitro conditions, PICF6 and PICF7 were only able to antagonize representative isolates of V. dahliae and V. longisporum. Remarkably, both strains produced an impressive portfolio of up to twenty VOCs, that included compounds with reported antifungal (e.g., 1-undecene, (methyldisulfanyl) methane and 1-decene) or plant growth promoting (e.g., tridecane, 1-decene) activities. Moreover, their volatilomes differed strongly in the absence and presence of V. dahliae.
For example, when co incubated with the defoliating pathotype of V. dahliae, the antifungal compound 4-methyl-2,6-bis(2-methyl-2-propanyl)phenol was produced. Results suggest that volatiles emitted by these endophytes may differ in their modes of action, and that potential benefits for the host needs further investigation in planta.
How tone, intonation and emotion shape the development of infants' fundamental frequency perception
(2022)
Fundamental frequency (integral(0)), perceived as pitch, is the first and arguably most salient auditory component humans are exposed to since the beginning of life.
It carries multiple linguistic (e.g., word meaning) and paralinguistic (e.g., speakers' emotion) functions in speech and communication.
The mappings between these functions and integral(0) features vary within a language and differ cross-linguistically. For instance, a rising pitch can be perceived as a question in English but a lexical tone in Mandarin. Such variations mean that infants must learn the specific mappings based on their respective linguistic and social environments.
To date, canonical theoretical frameworks and most empirical studies do not view or consider the multi-functionality of integral(0), but typically focus on individual functions. More importantly, despite the eventual mastery of integral(0) in communication, it is unclear how infants learn to decompose and recognize these overlapping functions carried by integral(0). In this paper, we review the symbioses and synergies of the lexical, intonational, and emotional functions that can be carried by integral(0) and are being acquired throughout infancy.
On the basis of our review, we put forward the Learnability Hypothesis that infants decompose and acquire multiple integral(0) functions through native/environmental experiences. Under this hypothesis, we propose representative cases such as the synergy scenario, where infants use visual cues to disambiguate and decompose the different integral(0) functions. Further, viable ways to test the scenarios derived from this hypothesis are suggested across auditory and visual modalities.
Discovering how infants learn to master the diverse functions carried by integral(0) can increase our understanding of linguistic systems, auditory processing and communication functions.
In-depth understanding of the reorganization of the hydrological cycle in response to global climate change is crucial in highly sensitive regions like the eastern Mediterranean, where water availability is a major factor for socioeconomic and political development.
The sediments of Lake Lisan provide a unique record of hydroclimatic change during the last glacial to Holocene transition (ca. 24-11 ka) with its tremendous water level drop of similar to 240 m that finally led to its transition into the present hypersaline water body-the Dead Sea.
Here we utilize high-resolution sedimentological analyses from the marginal terraces and deep lake to reconstruct an unprecedented seasonal record of the last millennia of Lake Lisan. Aragonite varve formation in intercalated intervals of our record demonstrates that a stepwise long-term lake level decline was interrupted by almost one millennium of rising or stable water level.
Even periods of pronounced water level drops indicated by gypsum deposition were interrupted by decades of positive water budgets.
Our results thus highlight that even during major climate change at the end of the last glacial, decadal to millennial periods of relatively stable or positive moisture supply occurred which could have been an important premise for human sedentism.
The Arctic is rich in aquatic systems and experiences rapid warming due to climate change. The accelerated warming causes permafrost thaw and the mobilization of organic carbon.
When dissolved organic carbon is mobilized, this DOC can be transported to aquatic systems and degraded in the water bodies and further downstream. Here, we analyze the influence of different landscape components on DOC concentrations and export in a small (6.45 km(2)) stream catchment in the Lena River Delta.
The catchment includes lakes and ponds, with the flow path from Pleistocene yedoma deposits across Holocene non-yedoma deposits to the river outlet. In addition to DOC concentrations, we use radiocarbon dating of DOC as well as stable oxygen and hydrogen isotopes (delta O-18 and delta D) to assess the origin of DOC.
We find significantly higher DOC concentrations in the Pleistocene yedoma area of the catchment compared to the Holocene non-yedoma area with medians of 5 and 4.5 mg L-1 (p < 0.05), respectively. When yedoma thaw streams with high DOC concentration reach a large yedoma thermokarst lake, we observe an abrupt decrease in DOC concentration, which we attribute to dilution and lake processes such as mineralization. The DOC ages in the large thermokarst lake (between 3,428 and 3,637 C-14 y BP) can be attributed to a mixing of mobilized old yedoma and Holocene carbon.
Further downstream after the large thermokarst lake, we find progressively younger DOC ages in the stream water to its mouth, paired with decreasing DOC concentrations. This process could result from dilution with leaching water from Holocene deposits and/or emission of ancient yedoma carbon to the atmosphere. Our study shows that thermokarst lakes and ponds may act as DOC filters, predominantly by diluting incoming waters of higher DOC concentrations or by re-mineralizing DOC to CO2 and CH4.
Nevertheless, our results also confirm that the small catchment still contributes DOC on the order of 1.2 kg km(-2) per day from a permafrost landscape with ice-rich yedoma deposits to the Lena River.
Consumers are increasingly demanding higher quality and safety standards for the products they consume, and one of this is wheat flour, the basis of a wide variety of processed products. This major component in the diet of many communities can be contaminated by microorganisms before the grain harvest, or during the grain storage right before processing. These microorganisms include several fungal species, many of which produce mycotoxins, secondary metabolites that can cause severe acute and chronic disorders. Yet, we still know little about the overall composition of fungal communities associated with wheat flour. In this study, we contribute to fill this gap by characterizing the fungal microbiome of different types of wheat flour using culture-dependent and -independent techniques. Qualitatively, these approaches suggested similar results, highlighting the presence of several fungal taxa able to produce mycotoxins. In-vitro isolation of fungal species suggest a higher frequency of Penicillium, while metabarcoding suggest a higher abundance of Alternaria. This discrepancy might reside on the targeted portion of the community (alive vs. overall) or in the specific features of each technique. Thus, this study shows that commercial wheat flour hosts a wide fungal diversity with several taxa potentially representing concerns for consumers, aspects that need more attention throughout the food production chain.
In Decolonizing Universalism: A Transnational Feminist Ethic zielt Serene Khader auf eine Neuausrichtung der feministischen Perspektive, welche es schafft, dekolonial und anti-imperialistisch zu sein, ohne gleichzeitig dem Universalismus komplett abzuschwören. Die Motivation hinter dieser Neuorientierung ist die Einsicht, dass der liberale moralische Universalismus oftmals kulturelle Vorherrschaft und Imperialismus verstärkt. In diesem Kommentar wollen wir (a) uns mit der Frage beschäftigen, was genau unter Geschlechtergerechtigkeit verstanden werden soll und welcher Maßstab zur Beantwortung der Frage nach Gerechtigkeit angebracht ist und (b) einige Ideen zum Unterschied zwischen idealer und nicht-idealer Theorie liefern.
Die Debatte um epistemische Ungerechtigkeit verbindet normative Gerechtigkeitstheorien mit erkenntnistheoretischen Theorien und stellt somit die Art von wichtigen Fragen, die in den letzten Jahren sowohl innerhalb als auch außerhalb der Wissenschaft internationale Aufmerksamkeit erfahren haben. Verwiesen sei hier etwa auf soziale Bewegungen wie #MeToo und #BlackLivesMatter zeigen. Theorien der epistemischen Ungerechtigkeit (sowie verwandte Theorien wie Epistemologie des Unwissens, feministische Erkenntnistheorie und Standpunkttheorie) können sowohl epistemische Praktiken analysieren und einen Beitrag zu Gerechtigkeitstheorien und sozialer Epistemologie liefern, als auch zu adäquateren Verständnissen von existierenden Ungerechtigkeiten beitragen. In dem hier vorliegenden Schwerpunkt werden Beiträge zu eben solchen bislang wenig erforschten Ungerechtigkeiten sowie neue Diskussionsbeiträge zur Debatte um epistemische Ungerechtigkeiten geliefert.
Assessing the impact of hydrogen absorption on the characteristics of the Galactic center excess
(2022)
We present a new reconstruction of the distribution of atomic hydrogen in the inner Galaxy that is based on explicit radiation transport modeling of line and continuum emission and a gas-flow model in the barred Galaxy that provides distance resolution for lines of sight toward the Galactic center.
The main benefits of the new gas model are (a) the ability to reproduce the negative line signals seen with the HI4PI survey and (b) the accounting for gas that primarily manifests itself through absorption.
We apply the new model of Galactic atomic hydrogen to an analysis of the diffuse gamma-ray emission from the inner Galaxy, for which an excess at a few GeV was reported that may be related to dark matter.
We find with high significance an improved fit to the diffuse gamma-ray emission observed with the Fermi-LAT, if our new H i model is used to estimate the cosmic-ray induced diffuse gamma-ray emission.
The fit still requires a nuclear bulge at high significance. Once this is included there is no evidence of a dark-matter signal, be it cuspy or cored. But an additional so-called boxy bulge is still favored by the data.
This finding is robust under the variation of various parameters, for example, the excitation temperature of atomic hydrogen, and a number of tests for systematic issues.