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The use of chironomids (Diptera: Chironomidae) as indicators of changes in natural and climatic settings allows one to reconstruct paleoclimatic and paleoenvironmental conditions. Based on the results of lithological and chironomid analyses, the loss on ignition (LOI) values, as well as the results of radiocarbon dating (C-14 AMS), new data on the paleoclimate in the Karelian Isthmus, in particular the quantitative reconstruction of the mean July temperature (T (July), A degrees C) in the Late Pleistocene and Holocene and the evolution of the ecosystem of Medvedevskoe Lake have been obtained.
Aims/hypothesis Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. Methods We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Results Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure. Conclusion/interpretation Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.
Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
Spatial-numerical associations (SNAs) have been studied extensively in the past two decades, always requiring either explicit magnitude processing or explicit spatial-directional processing. This means that the typical finding of an association of small numbers with left or bottom space and of larger numbers with right or top space could be due to these requirements and not the conceptual representation of numbers. The present study compares explicit and implicit magnitude processing in an implicit spatial-directional task and identifies SNAs as artefacts of either explicit magnitude processing or explicit spatial-directional processing; they do not reveal spatial conceptual links. This finding requires revision of current accounts of the relationship between numbers and space.
Lactose is of great industrial importance and its production includes the cooling crystallization from highly concentrated solutions. Monitoring the crystallization process is essential to ensure reproducible product quality. Photon density wave (PDW) spectroscopy enables in-line monitoring of highly concentrated processes in liquid dispersions. It was applied to the determination of the solubility and nucleation points of lactose monohydrate in water, sizing of lactose crystals, and to dissolution as well as crystallization monitoring. Other process analytical technologies (focused-beam reflectance measurement, particle vision and measurement) were used as reference, and the comparison indicates that PDW spectroscopy is very robust against probe fouling and is, thus, a useful tool for monitoring crystallization processes in concentrated suspensions.
There are few data analysing to what specific extent phonomicrosurgery improves vocal function in patients suffering from Reinke's oedema (RE). The recently introduced parameter vocal extent measure (VEM) seems to be suitable to objectively quantify vocal performance. The purpose of this clinical prospective study was to investigate the outcomes of phonomicrosurgery in 60 RE patients (6 male, 54 female; 56 ± 8 years ([mean ± SD]) by analysing its effect on subjective and objective vocal parameters with particular regard to VEM. Treatment efficacy was evaluated at three months after surgery by comparing pre- and postoperative videolaryngostroboscopy (VLS), auditory-perceptual assessment (RBH-status), voice range profile (VRP), acoustic-aerodynamic analysis and patient's self-assessment using the voice handicap index (VHI-9i). Phonomicrosurgically, all RE were carefully ablated. VLS revealed removal or substantial reduction of oedema with restored periodic vocal fold vibration. All subjective and most objective acoustic and aerodynamic parameters significantly improved. The VEM increased on average from 64 ± 37 to 88 ± 25 (p #x003C; 0.001) and the dysphonia severity index (DSI) from 0.5 ± 3.4 to 2.9 ± 1.9. Both parameters correlated significantly with each other (rs = 0.70). RBH-status revealed less roughness, breathiness and overall grade of hoarseness (2.0 ± 0.7 vs 1.3 ± 0.7). The VHI-9i-score decreased from 18 ± 8 to 12 ± 9 points. The average total vocal range enlarged by 4 ± 7 semitones, and the mean speaking pitch rose by 2 ± 4 semitones. These results confirm that: (1) the use of VEM in RE patients objectifies and quantifies their vocal capacity as documented in the VRP, and (2) phonomicrosurgery is an effective, objectively and subjectively satisfactory therapy to improve voice in RE patients.
In aquatic ecosystems, light availability can significantly influence microbial turnover of terrestrial organic matter through associated metabolic interactions between phototrophic and heterotrophic communities. However, particularly in streams, microbial functions vary significantly with the structure of the streambed, that is the distribution and spatial arrangement of sediment grains in the streambed. It is therefore essential to elucidate how environmental factors synergistically define the microbial turnover of terrestrial organic matter in order to better understand the ecological role of photoheterotrophic interactions in stream ecosystem processes. In outdoor experimental streams, we examined how the structure of streambeds modifies the influence of light availability on microbial turnover of leaf carbon (C). Furthermore, we investigated whether the studied relationships of microbial leaf C turnover to environmental conditions are affected by flow intermittency commonly occurring in streams. We applied leaves enriched with a C-13-stable isotope tracer and combined quantitative and isotope analyses. We thereby elucidated whether treatment induced changes in C turnover were associated with altered use of leaf C within the microbial food web. Moreover, isotope analyses were combined with measurements of microbial community composition to determine whether changes in community function were associated with a change in community composition. In this study, we present evidence, that environmental factors interactively determine how phototrophs and heterotrophs contribute to leaf C turnover. Light availability promoted the utilization of leaf C within the microbial food web, which was likely associated with a promoted availability of highly bioavailable metabolites of phototrophic origin. However, our results additionally confirm that the structure of the streambed modifies light-related changes in microbial C turnover. From our observations, we conclude that the streambed structure influences the strength of photo-heterotrophic interactions by defining the spatial availability of algal metabolites in the streambed and the composition of microbial communities. Collectively, our multifactorial approach provides valuable insights into environmental controls on the functioning of stream ecosystems.
In this study, we analyzed 10 yrs of seismicity in central Italy from 2008 to 2017, a period witnessing more than 1400 earthquakes in the magnitude range 2.5≤Mw≤6.5. The data set includes the main sequences that have occurred in the area, including those associated with the 2009 Mw 6.3 L'Aquila earthquake and the 2016–2017 sequence (Mw 6.2 Amatrice, Mw 6.1 Visso, and Mw 6.5 Norcia earthquakes). We calibrated a local magnitude scale, investigating the impact of changing the reference distance at which the nonparametric attenuation is tied to the zero‐magnitude attenuation function for southern California. We also developed an attenuation model to compute the radiated seismic energy (Es) from the time integral of the squared ground‐motion velocity. Seismic moment (M0) and stress drop (Δσ) were estimated for each earthquake by fitting a ω‐square model to the source spectra obtained by applying a nonparametric spectral inversion. The Δσ‐values vary over three orders of magnitude from about 0.1 to 10 MPa, the larger values associated with the mainshocks. The Δσ‐values describe a lognormal distribution with mean and standard deviation equal to log(Δσ)=(−0.25±0.45) (i.e., the mean Δσ is 0.57 MPa, with a 95% confidence interval from 0.08 to 4.79 MPa). The Δσ variability introduces a spread in the distribution of seismic energy versus moment, with differences in energy up two orders of magnitudes for earthquakes with the same moment. The variability in the high‐frequency spectral levels is captured by the local magnitude (ML), which scales with radiated energy as ML=(−1.59+0.52logEs) for logEs≤10.26 and ML=(−1.38+0.50logEs) otherwise. As the peak ground velocity increases with increasing Δσ, local and energy magnitudes perform better than moment magnitude as predictors for the shaking potential. The availability of different magnitude scales and source parameters for a large earthquake population will help characterize the between‐event ground‐motion variability in central Italy.
Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis of PPMS and its differentiation from the relapsing remitting subtype (RRMS), primary neurodegenerative disease (Parkinson’s disease, PD), and healthy controls (HCs) and that significantly change during the disease course and could serve as surrogate markers of multiple sclerosis (MS)-associated neurodegeneration over time. We applied untargeted high-resolution metabolomics to plasma samples to identify PPMS-specific signatures, validated our findings in independent sex- and age-matched PPMS and HC cohorts and built discriminatory models by partial least square discriminant analysis (PLS-DA). This signature was compared to sex- and age-matched RRMS patients, to patients with PD and HC. Finally, we investigated these metabolites in a longitudinal cohort of PPMS patients over a 24-month period. PLS-DA yielded predictive models for classification along with a set of 20 PPMS-specific informative metabolite markers. These metabolites suggest disease-specific alterations in glycerophospholipid and linoleic acid pathways. Notably, the glycerophospholipid LysoPC(20:0) significantly decreased during the observation period. These findings show potential for diagnosis and disease course monitoring, and might serve as biomarkers to assess treatment efficacy in future clinical trials for neuroprotective MS therapies.
Cell-free protein synthesis as a novel tool for directed glycoengineering of active erythropoietin
(2018)
As one of the most complex post-translational modification, glycosylation is widely involved in cell adhesion, cell proliferation and immune response. Nevertheless glycoproteins with an identical polypeptide backbone mostly differ in their glycosylation patterns. Due to this heterogeneity, the mapping of different glycosylation patterns to their associated function is nearly impossible. In the last years, glycoengineering tools including cell line engineering, chemoenzymatic remodeling and site-specific glycosylation have attracted increasing interest. The therapeutic hormone erythropoietin (EPO) has been investigated in particular by various groups to establish a production process resulting in a defined glycosylation pattern. However commercially available recombinant human EPO shows batch-to-batch variations in its glycoforms. Therefore we present an alternative method for the synthesis of active glycosylated EPO with an engineered O-glycosylation site by combining eukaryotic cell-free protein synthesis and site-directed incorporation of non-canonical amino acids with subsequent chemoselective modifications.
Context. Classic massive binary evolutionary scenarios predict that a transitional common-envelope (CE) phase could be preceded as well as succeeded by the evolutionary stage when a binary consists of a compact object and a massive star, that is, a high-mass X-ray binary (HMXB). The observational manifestations of common envelope are poorly constrained. We speculate that its ejection might be observed in some cases as a transient event at mid-infrared (IR) wavelengths. Aims. We estimate the expected numbers of CE ejection events and HMXBs per star formation unit rate, and compare these theoretical estimates with observations. Methods. We compiled a list of 85 mid-IR transients of uncertain nature detected by the Spitzer Infrared Intensive Transients Survey and searched for their associations with X-ray, optical, and UV sources. Results. Confirming our theoretical estimates, we find that only one potential HMXB may be plausibly associated with an IR-transient and tentatively propose that X-ray source NGC4490-X40 could be a precursor to the SPIRITS 16az event. Among other interesting sources, we suggest that the supernova remnant candidate [BWL2012] 063 might be associated with SPIRITS 16ajc. We also find that two SPIRITS events are likely associated with novae, and seven have potential optical counterparts. Conclusions. The massive binary evolutionary scenarios that involve CE events do not contradict currently available observations of IR transients and HMXBs in star-forming galaxies.
A prelude to total war?
(2018)
The conflict between Italy and Ethiopia in 1935–36 has been framed as a prelude to the Second World War and as a watershed towards ‘Total War’. One perspective has so far been neglected: the assessments of foreign military observers. This article examines American, British, German, and Austrian views on the operations and thereby also analyses the mindset of European officers at the time. The core argument emerging from these reports is that the war was perceived as a rather ‘normal’ colonial conflict. Neither the use of gas, nor the employment of aircraft against civilians was seen as a taboo or created significant outrage among the military observers. Instead, they lauded the Italians’ steady logistical efforts and employment of artillery and airpower to overcome nature and the enemy’s resistance.
Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange. On a tissue-scale, PCP signalling planar-polarises tissue tension by restricting the actomyosin contractility to the apical membranes of outflow tract cells. The tissue-scale polarisation of actomyosin contractility is required for cardiac looping that occurs concurrently with chamber ballooning. Taken together, our data reveal that instructive PCP signals couple cardiac chamber expansion with cardiac looping through the organ-scale polarisation of actomyosin-based tissue tension.
Ice-wedge polygons are widespread periglacial features and influence landscape hydrology and carbon storage. The influence of climate and topography on polygon development is not entirely clear, however, giving high uncertainties to projections of permafrost development. We studied the mid- to late Holocene development of modern ice-wedge polygon sites to explore drivers of change and reasons for long-term stability. We analyzed organic carbon, total nitrogen, stable carbon isotopes, grain size composition and plant macrofossils in six cores from three polygons. We found that ail sites developed from aquatic to wetland conditions. In the mid-Holocene, shallow lakes and partly submerged ice-wedge polygons existed at the studied sites. An erosional hiatus of ca 5000 years followed, and ice-wedge polygons re-initiated within the last millennium. Ice-wedge melt and surface drying during the last century were linked to climatic warming. The influence of climate on ice-wedge polygon development was outweighed by geomorphology during most of the late Holocene. Recent warming, however, caused ice-wedge degradation at all sites. Our study showed that where waterlogged ground was maintained, low-centered polygons persisted for millennia. Ice-wedge melt and increased drainage through geomorphic disturbance, however, triggered conversion into high-centered polygons and may lead to self-enhancing degradation under continued warming.
The bowshocks of runaway stars had been theoretically proposed as gamma-ray sources. However, this hypothesis has not been confirmed by observations to date. In this paper, we present two runaway stars (lambda Cep and LS 2355) whose bowshocks are coincident with the unidentified Fermi gamma-ray sources 3FLG J2210.1+5925 and 3FGL J1128.7-6232, respectively. After performing a cross-correlation between different catalogs at distinct wavelengths, we found that these bowshocks are the most peculiar objects in the Fermi position ellipses. Then we computed the inverse Compton emission and fitted the Fermi data in order to test the viability of both runaway stars as potential counterparts of the two high-energy sources. We obtained very reasonable values for the fitted parameters of both stars. We also evaluated the possibility for the source 3FGL J1128.7-6232, which is positionally coincident with a H II region, to be the result of background cosmic-ray protons interacting with the matter of the cloud, as well as the probability of a pure chance association. We conclude that the gamma rays from these Fermi sources might be produced in the bowshocks of the considered runaway stars. In such a case, these would be the first sources of this class ever detected at gamma rays.
The pace-of-life syndrome (i.e., POLS) hypothesis posits that behavioral and physiological traits mediate the trade-off between current and future reproduction. This hypothesis predicts that life history, behavioral, and physiological traits will covary under clearly defined conditions. Empirical tests are equivocal and suggest that the conditions necessary for the POLS to emerge are not always met. We nuance and expand the POLS hypothesis to consider alternative relationships among behavior, physiology, and life history. These relationships will vary with the nature of predation risk, the challenges posed by resource acquisition, and the energy management strategies of organisms. We also discuss how the plastic response of behavior, physiology, and life history to changes in ecological conditions and variation in resource acquisition among individuals determine our ability to detect a fast-slow pace of life in the first place or associations among these traits. Future empirical studies will provide most insights on the coevolution among behavior, physiology, and life history by investigating these traits both at the genetic and phenotypic levels in varying types of predation regimes and levels of resource abundance.
Quantifying the pace of ice-sheet growth is critical to understanding ice-age climate and dynamics. Here, we show that the diversion of the Hudson River (northeastern North America) late in the last glaciation phase (ca. 30 ka), which some previous studies have speculated was due to glacial isostatic adjustment (GIA), can be used to infer the timing of the Laurentide Ice Sheet’s growth to its maximum extent. Landscapes in the vicinity of glaciated regions have likely responded to crustal deformation produced by ice-sheet growth and decay through river drainage reorganization, given that rates of uplift and subsidence are on the order of tens of meters per thousand years. We perform global, gravitationally self-consistent simulations of GIA and input the predicted crustal deformation field into a landscape evolution model. Our calculations indicate that the eastward diversion of the Hudson River at 30 ka is consistent with exceptionally rapid growth of the Laurentide Ice Sheet late in the glaciation phase, beginning at 50–35 ka.
Self-assembling features of sodium dioctyl sulfosuccinate (AOT) molecules and micelle adsorption on gold Au (111) surfaces have been examined using molecular dynamics simulation. We argue that AOT micelles display a strong adsorption on gold surfaces resulting in distorted cylindrical micelles attached to the (111) facets. The well protected Au(111) facets decorated by a dense packed elongated ellipsoidal AOT layer hinder the diffusion of the reactant to the (111) facets and could result in the preferential growth of ultra-thin gold nanoplatelets.
Two-dimensional modeling of density and thermal structure of dense circumstellar outflowing disks
(2018)
Context. Evolution of massive stars is affected by a significant loss of mass either via (nearly) spherically symmetric stellar winds or by aspherical mass-loss mechanisms, namely the outflowing equatorial disks. However, the scenario that leads to the formation of a disk or rings of gas and dust around massive stars is still under debate. It is also unclear how various forming physical mechanisms of the circumstellar environment affect its shape and density, as well as its kinematic and thermal structure. Results. Our models show the geometric distribution and contribution of viscous heating that begins to dominate in the central part of the disk for mass-loss rates higher than (M) over dot greater than or similar to 10(-10) M-circle dot yr(-1). In the models of dense viscous disks with (M) over dot > 10(-8) M-circle dot yr(-1), the viscosity increases the central temperature up to several tens of thousands of Kelvins, however the temperature rapidly drops with radius and with distance from the disk midplane. The high mass-loss rates and high viscosity lead to instabilities with significant waves or bumps in density and temperature in the very inner disk region. Conclusions. The two-dimensional radial-vertical models of dense outflowing disks including the full Navier-Stokes viscosity terms show very high temperatures that are however limited to only the central disk cores inside the optically thick area, while near the edge of the optically thick region the temperature may be low enough for the existence of neutral hydrogen, for example.
From a health and performance-related perspective, it is crucial to evaluate subjective symptoms and objective signs of acute training-induced immunological responses in young athletes. The limited number of available studies focused on immunological adaptations following aerobic training. Hardly any studies have been conducted on resistance-training induced stress responses. Therefore, the aim of this observational study was to investigate subjective symptoms and objective signs of immunological stress responses following resistance training in young athletes. Fourteen (7 females and 7 males) track and field athletes with a mean age of 16.4 years and without any symptoms of upper or lower respiratory tract infections participated in this study. Over a period of 7 days, subjective symptoms using the Acute Recovery and Stress Scale (ARSS) and objective signs of immunological responses using capillary blood markers were taken each morning and after the last training session. Differences between morning and evening sessions and associations between subjective and objective parameters were analyzed using generalized estimating equations (GEE). In post hoc analyses, daily change-scores of the ARSS dimensions were compared between participants and revealed specific changes in objective capillary blood samples. In the GEE models, recovery (ARSS) was characterized by a significant decrease while stress (ARSS) showed a significant increase between morning and evening-training sessions. A concomitant increase in white blood cell count (WBC), granulocytes (GRAN) and percentage shares of granulocytes (GRAN%) was found between morning and evening sessions. Of note, percentage shares of lymphocytes (LYM%) showed a significant decrease. Furthermore, using multivariate regression analyses, we identified that recovery was significantly associated with LYM%, while stress was significantly associated with WBC and GRAN%. Post hoc analyses revealed significantly larger increases in participants' stress dimensions who showed increases in GRAN%. For recovery, significantly larger decreases were found in participants with decreases in LYM% during recovery. More specifically, daily change-scores of the recovery and stress dimensions of the ARSS were associated with specific changes in objective immunological markers (GRAN%, LYM%) between morning and evening-training sessions. Our results indicate that changes of subjective symptoms of recovery and stress dimensions using the ARSS were associated with specific changes in objectively measured immunological markers.