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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.
Air pollution is a pressing issue that is associated with adverse effects on human health, ecosystems, and climate. Despite many years of effort to improve air quality, nitrogen dioxide (NO2) limit values are still regularly exceeded in Europe, particularly in cities and along streets. This study explores how concentrations of nitrogen oxides (NOx = NO + NO2) in European urban areas have changed over the last decades and how this relates to changes in emissions. To do so, the incremental approach was used, comparing urban increments (i.e. urban background minus rural concentrations) to total emissions, and roadside increments (i.e. urban roadside concentrations minus urban background concentrations) to traffic emissions. In total, nine European cities were assessed. The study revealed that potentially confounding factors like the impact of urban pollution at rural monitoring sites through atmospheric transport are generally negligible for NOx. The approach proves therefore particularly useful for this pollutant. The estimated urban increments all showed downward trends, and for the majority of the cities the trends aligned well with the total emissions. However, it was found that factors like a very densely populated surrounding or local emission sources in the rural area such as shipping traffic on inland waterways restrict the application of the approach for some cities. The roadside increments showed an overall very diverse picture in their absolute values and trends and also in their relation to traffic emissions. This variability and the discrepancies between roadside increments and emissions could be attributed to a combination of local influencing factors at the street level and different aspects introducing inaccuracies to the trends of the emis-sion inventories used, including deficient emission factors. Applying the incremental approach was evaluated as useful for long-term pan-European studies, but at the same time it was found to be restricted to certain regions and cities due to data availability issues. The results also highlight that using emission inventories for the prediction of future health impacts and compliance with limit values needs to consider the distinct variability in the concentrations not only across but also within cities.
Narcissists are assumed to lack the motivation and ability to share and understand the mental states of others. Prior empirical research, however, has yielded inconclusive findings and has differed with respect to the specific aspects of narcissism and socioemotional cognition that have been examined. Here, we propose a differentiated facet approach that can be applied across research traditions and that distinguishes between facets of narcissism (agentic vs. antagonistic) on the one hand, and facets of socioemotional cognition ability (SECA; self-perceived vs. actual) on the other. Using five nonclinical samples in two studies (total N = 602), we investigated the effect of facets of grandiose narcissism on aspects of socioemotional cognition across measures of affective and cognitive empathy, Theory of Mind, and emotional intelligence, while also controlling for general reasoning ability. Across both studies, agentic facets of narcissism were found to be positively related to perceived SECA, whereas antagonistic facets of narcissism were found to be negatively related to perceived SECA. However, both narcissism facets were negatively related to actual SECA. Exploratory condition-based regression analyses further showed that agentic narcissists had a higher directed discrepancy between perceived and actual SECA: They self-enhanced their socio-emotional capacities. Implications of these results for the multifaceted theoretical understanding of the narcissism-SECA link are discussed.
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.
Apoptotic death of cells damaged by genotoxic stress requires regulatory input from surrounding tissues. The C. elegans scaffold protein KRI-1, ortholog of mammalian KRIT1/CCM1, permits DNA damage-induced apoptosis of cells in the germline by an unknown cell non-autonomous mechanism. We reveal that KRI-1 exists in a complex with CCM-2 in the intestine to negatively regulate the ERK-5/MAPK pathway. This allows the KLF-3 transcription factor to facilitate expression of the SLC39 zinc transporter gene zipt-2.3, which functions to sequester zinc in the intestine. Ablation of KRI-1 results in reduced zinc sequestration in the intestine, inhibition of IR-induced MPK-1/ERK1 activation, and apoptosis in the germline. Zinc localization is also perturbed in the vasculature of krit1(-/-) zebrafish, and SLC39 zinc transporters are mis-expressed in Cerebral Cavernous Malformations (CCM) patient tissues. This study provides new insights into the regulation of apoptosis by cross-tissue communication, and suggests a link between zinc localization and CCM disease.
Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.
Model-informed precision dosing (MIPD) is a quantitative dosing framework that combines prior knowledge on the drug-disease-patient system with patient data from therapeutic drug/ biomarker monitoring (TDM) to support individualized dosing in ongoing treatment. Structural models and prior parameter distributions used in MIPD approaches typically build on prior clinical trials that involve only a limited number of patients selected according to some exclusion/inclusion criteria. Compared to the prior clinical trial population, the patient population in clinical practice can be expected to also include altered behavior and/or increased interindividual variability, the extent of which, however, is typically unknown. Here, we address the question of how to adapt and refine models on the level of the model parameters to better reflect this real-world diversity. We propose an approach for continued learning across patients during MIPD using a sequential hierarchical Bayesian framework. The approach builds on two stages to separate the update of the individual patient parameters from updating the population parameters. Consequently, it enables continued learning across hospitals or study centers, because only summary patient data (on the level of model parameters) need to be shared, but no individual TDM data. We illustrate this continued learning approach with neutrophil-guided dosing of paclitaxel. The present study constitutes an important step toward building confidence in MIPD and eventually establishing MIPD increasingly in everyday therapeutic use.
National Action Plans (NAPs) have been increas-ingly adopted world-wide after the Vienna Dec-laration in 1993, where it was urged to consider the improvement and promotion of Human Rights. In this paper, we discuss their usefulness and success by analysing the challenges present-ed during NAP processes as well as the benefits this set of actions entails: The challenges for their implementation outweigh its actual benefits. Nevertheless, NAPs have great potential. Based on new research, we elaborate a set of recom-mendations for improving the design and imple-mentation of national action planning. In order to effectively bring NAP into practice, we consider it crucial to plan and analyse every state local circumstances in detail. The latter is important, since the implementation of a concrete set of actions is intended to directly transform and improve the local living conditions of the people. In a long-term perspective, we defend the benefit of NAP’s implementation for complying obliga-tions set up by HR treaties.
The last years have been affected by Covid-19 and the international emergency mecha-nism to deal with health-related threats. The effects of this period manifested differ-ently worldwide, depending on matters such as international relations, national policies, power dynamics etc. Additionally, the impact of this time will likely have long-term effects which are yet to be known. This paper gives a critical overview of the Public Health Emergency of International Concern (PHEIC) mechanism in the context of Covid-19. It does so by explaining the legal framework for states of emergency, specifically in the context of a PHEIC, while considering its restrictions and limitations on human rights. It further outlines issues in the manifestation of global protections and limitations on human rights during Covid-19. Lastly, considering the likelihood of future PHEICs and the known systemic obstructions, this paper offers ways to im-prove this mechanism from a holistic, non-zero-sum perspective.
Compound natural hazards likeEl Ninoevents cause high damage to society, which to manage requires reliable risk assessments. Damage modelling is a prerequisite for quantitative risk estimations, yet many procedures still rely on expert knowledge, and empirical studies investigating damage from compound natural hazards hardly exist. A nationwide building survey in Peru after theEl Ninoevent 2017 - which caused intense rainfall, ponding water, flash floods and landslides - enables us to apply data-mining methods for statistical groundwork, using explanatory features generated from remote sensing products and open data. We separate regions of different dominant characteristics through unsupervised clustering, and investigate feature importance rankings for classifying damage via supervised machine learning. Besides the expected effect of precipitation, the classification algorithms select the topographic wetness index as most important feature, especially in low elevation areas. The slope length and steepness factor ranks high for mountains and canyons. Partial dependence plots further hint at amplified vulnerability in rural areas. An example of an empirical damage probability map, developed with a random forest model, is provided to demonstrate the technical feasibility.
A expulsão do Éden
(2021)
A temática da migração está intimamente vinculada à história humana, desde a narrativa bíblica da expulsão do paraíso. O ser humano não apenas empregou técnicas cada vez mais sofisticadas para a violência, como também transmitiu, através dos séculos, técnicas de conservação e uso de seu saberconviver. Nesse sentido móvel da história, e em consonância com as literaturas do mundo, a partir de suas diversas origens, é possível dizer que existe um “Homo migrans” desde que existe o “Homo sapiens”. Assim, é possível afirmar que as ideias territoriais ou territorializantes com proveniência histórico-espacial permitem, vez ou outra, reconhecer seus esforços para filtrar e isolar a dimensão histórico-móvel e vetorial da história como narrativa, para tentar construir, com a ajuda de ideias estáticas, novos lugares da promessa ou da perda, da abundância ou da queda.
A familial congenital heart disease with a possible multigenic origin involving a mutation in BMPR1A
(2019)
The genetics of many congenital heart diseases (CHDs) can only unsatisfactorily be explained by known chromosomal or Mendelian syndromes. Here, we present sequencing data of a family with a potentially multigenic origin of CHD. Twelve of nineteen family members carry a familial mutation [NM_004329.2:c.1328 G > A (p.R443H)] which encodes a predicted deleterious variant of BMPR1A. This mutation co-segregates with a linkage region on chromosome 1 that associates with the emergence of severe CHDs including Ebstein’s anomaly, atrioventricular septal defect, and others. We show that the continuous overexpression of the zebrafish homologous mutation bmpr1aap.R438H within endocardium causes a reduced AV valve area, a downregulation of Wnt/ß-catenin signalling at the AV canal, and growth of additional tissue mass in adult zebrafish hearts. This finding opens the possibility of testing genetic interactions between BMPR1A and other candidate genes within linkage region 1 which may provide a first step towards unravelling more complex genetic patterns in cardiovascular disease aetiology.
Biogenic greenhouse gas emissions, e.g., of methane (CH4) and carbon dioxide (CO2) from inland waters, contribute substantially to global warming. In aquatic systems, dissolved greenhouse gases are highly heterogeneous in both space and time. To better understand the biological and physical processes that affect sources and sinks of both CH4 and CO2, their dissolved concentrations need to be measured with high spatial and temporal resolution. To achieve this goal, we developed the Fast-Response Automated Gas Equilibrator (FaRAGE) for real-time in situ measurement of dissolved CH4 and CO2 concentrations at the water surface and in the water column. FaRAGE can achieve an exceptionally short response time (t(95%) = 12 s when including the response time of the gas analyzer) while retaining an equilibration ratio of 62.6% and a measurement accuracy of 0.5% for CH4. A similar performance was observed for dissolved CO2 (t(95%) = 10 s, equilibration ratio 67.1 %). An equilibration ratio as high as 91.8% can be reached at the cost of a slightly increased response time (16 s). The FaRAGE is capable of continuously measuring dissolved CO2 and CH4 concentrations in the nM-to-submM (10(-9)-10(-3) mol L-1) range with a detection limit of subnM (10(-10) mol L-1), when coupling with a cavity ring-down greenhouse gas analyzer (Picarro GasScouter). FaRAGE allows for the possibility of mapping dissolved concentration in a "quasi" three-dimensional manner in lakes and provides an inexpensive alternative to other commercial gas equilibrators. It is simple to operate and suitable for continuous monitoring with a strong tolerance for suspended particles. While the FaRAGE is developed for inland waters, it can be also applied to ocean waters by tuning the gas-water mixing ratio. The FaRAGE is easily adapted to suit other gas analyzers expanding the range of potential applications, including nitrous oxide and isotopic composition of the gases.
The investigation of metabolic fluxes and metabolite distributions within cells by means of tracer molecules is a valuable tool to unravel the complexity of biological systems. Technological advances in mass spectrometry (MS) technology such as atmospheric pressure chemical ionization (APCI) coupled with high resolution (HR), not only allows for highly sensitive analyses but also broadens the usefulness of tracer-based experiments, as interesting signals can be annotated de novo when not yet present in a compound library. However, several effects in the APCI ion source, i.e., fragmentation and rearrangement, lead to superimposed mass isotopologue distributions (MID) within the mass spectra, which need to be corrected during data evaluation as they will impair enrichment calculation otherwise. Here, we present and evaluate a novel software tool to automatically perform such corrections. We discuss the different effects, explain the implemented algorithm, and show its application on several experimental datasets. This adjustable tool is available as an R package from CRAN.
This work reviews the literature on an alleged global warming 'pause' in global mean surface temperature (GMST) to determine how it has been defined, what time intervals are used to characterise it, what data are used to measure it, and what methods used to assess it. We test for 'pauses', both in the normally understood meaning of the term to mean no warming trend, as well as for a 'pause' defined as a substantially slower trend in GMST. The tests are carried out with the historical versions of GMST that existed for each pause-interval tested, and with current versions of each of the GMST datasets. The tests are conducted following the common (but questionable) practice of breaking the linear fit at the start of the trend interval ('broken' trends), and also with trends that are continuous with the data bordering the trend interval. We also compare results when appropriate allowance is made for the selection bias problem. The results show that there is little or no statistical evidence for a lack of trend or slower trend in GMST using either the historical data or the current data. The perception that there was a 'pause' in GMST was bolstered by earlier biases in the data in combination with incomplete statistical testing.
Although the use of stable transformation technology has led to great insight into gene function, its application in high-throughput studies remains arduous. Agro-infiltration have been widely used in species such as Nicotiana benthamiana for the rapid detection of gene expression and protein interaction analysis, but this technique does not work efficiently in other plant species, including Arabidopsis thaliana. As an efficient high-throughput transient expression system is currently lacking in the model plant species A. thaliana, we developed a method that is characterized by high efficiency, reproducibility, and suitability for transient expression of a variety of functional proteins in A. thaliana and 7 other plant species, including Brassica oleracea, Capsella rubella, Thellungiella salsuginea, Thellungiella halophila, Solanum tuberosum, Capsicum annuum, and N. benthamiana. Efficiency of this method was independently verified in three independent research facilities, pointing to the robustness of this technique. Furthermore, in addition to demonstrating the utility of this technique in a range of species, we also present a case study employing this method to assess protein-protein interactions in the sucrose biosynthesis pathway in Arabidopsis.
A few months before his death, A. v. Humboldt attended the celebration in honor of the 127th birthday of George Washington at the US legation in Berlin. A letter to the American Envoy, Joseph A. Wright (1810 – 1867), underlines Humboldt’s admiration for the fi rst president of the United States. At the same time Humboldt asked the diplomat to mail a letter to the German-American Bernard Moses (1832 – 1897) in Clinton, Louisiana, who had named his son Alexander Humboldt Moses (grave on the Hebrew Rest Cemetery #2 in New Orleans, burial plot A, 12, 5). It appears to be possible that the Moses family still owns Humboldt’s letter.
Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption.
Aging in speech production is a multidimensional process. Biological, cognitive, social, and communicative factors can change over time, stay relatively stable, or may even compensate for each other. In this longitudinal work, we focus on stability and change at the laryngeal and supralaryngeal levels in the discourse particle euh produced by 10 older French-speaking females at two times, 10 years apart. Recognizing the multiple discourse roles of euh, we divided out occurrences according to utterance position. We quantified the frequency of euh, and evaluated acoustic changes in formants, fundamental frequency, and voice quality across time and utterance position. Results showed that euh frequency was stable with age. The only acoustic measure that revealed an age effect was harmonics-to-noise ratio, showing less noise at older ages. Other measures mostly varied with utterance position, sometimes in interaction with age. Some voice quality changes could reflect laryngeal adjustments that provide for airflow conservation utterance-finally. The data suggest that aging effects may be evident in some prosodic positions (e.g., utterance-final position), but not others (utterance-initial position). Thus, it is essential to consider the interactions among these factors in future work and not assume that vocal aging is evident throughout the signal.