bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inventa: a computational tool to discover chemical novelty in natural extracts libraries
Authors: Quiros-Guerrero Luis-Manuel , Nothias Louis-Félix , Gaudry Arnaud , Marcourt Laurence , Allard Pierre-Marie , Rutz Adriano , David Bruno , Queiroz Emerson Ferreira , Wolfender Jean-Luc 
Published: August 2022

AbstractCollections of natural extracts hold potential for the discovery of novel natural products with original modes of action. The prioritization of extracts from collections remains challenging due to the lack of workflow that combines multiple-source information to facilitate the data interpretation. Results from different analysis techniques and literature reports need to be organized, processed, and interpreted to enable optimal decision-making for extracts prioritization. Here, we introduce Inventa, a computational tool that highlights the chemical novelty potential within extracts, considering untargeted mass spectrometry data, spectral annotation, and literature reports. Based on this information, Inventa calculates multiple scores that inform their chemical potential. Thus, Inventa has the potential to accelerate new natural products discovery. Inventa was applied to a set of plants from the Celastraceae family as a proof of concept. The Pristimera indica (Willd.) A.C.Sm roots extract was highlighted as a promising source of potentially novel compounds. Its phytochemical investigation resulted in the isolation and de novo characterization of thirteen new dihydro-β-agarofuran sesquiterpenes, five of them presenting a new 9-oxodihydro-β-agarofuran base scaffold.
Dispersal inference from population genetic variation using a convolutional neural network
Authors: Smith Chris C. R. , Tittes Silas , Ralph Peter L. , Kern Andrew D. 
Published: August 2022

AbstractThe geographic nature of biological dispersal shapes patterns of genetic variation over landscapes, making it possible to infer properties of dispersal from genetic variation data. Here we present an inference tool that uses geographically distributed genotype data in combination with a convolutional neural network to estimate a critical population parameter: the mean per-generation dispersal distance. Using extensive simulation, we show that our deep learning approach is competitive with or outperforms state-of-the-art methods, particularly at small sample sizes. In addition, we evaluate varying nuisance parameters during training—including population density, demographic history, habitat size, and sampling area—and show that this strategy is effective for estimating dispersal distance when other model parameters are unknown. Whereas competing methods depend on information about local population density or accurate identification of identity-by-descent tracts, our method uses only single-nucleotide-polymorphism data and the spatial scale of sampling as input. Strikingly, and unlike other methods, our method does not use the geographic coordinates of the genotyped individuals. These features make our method, which we call “disperseNN”, a potentially valuable new tool for estimating dispersal distance in non-model systems with whole genome data or reduced representation data. We applydisperseNNto 12 different species with publicly available data, yielding reasonable estimates for most species. Importantly, our method estimated consistently larger dispersal distances than mark-recapture calculations in the same species, which may be due to the limited geographic sampling area covered by some mark-recapture studies. Thus genetic tools like ours complement direct methods for improving our understanding of dispersal.
Human senataxin is a bona fide R-loop resolving enzyme and transcription termination factor
Authors: Hasanova Zdenka , Klapstova Veronika , Porrua Odil , Stefl Richard , Sebesta Marek 
Published: August 2022

ABSTRACTProlonged pausing of the transcription machinery may lead to the formation of three-stranded nucleic acid structures, called R-loops, typically resulting from the annealing of the nascent RNA with the template DNA. Unscheduled persistence of R-loops and RNA polymerases may interfere with transcription itself and other essential processes such as DNA replication and repair. Senataxin (SETX) is a putative helicase, mutated in two neurodegenerative disorders, which has been implicated in the control of R-loop accumulation and in transcription termination. However, understanding the precise role of SETX in these processes has been precluded by the absence of a direct characterisation of SETX biochemical activities. Here, we purify and characterise the helicase domain of SETX in parallel with its yeast orthologue, Sen1. Importantly, we show that SETX is a bona fide helicase with the ability to resolve R-loops. Furthermore, SETX has retained the transcription termination activity of Sen1 but functions in a species-specific manner. Finally, subsequent characterisation of two SETX variants harbouring disease-associated mutations shed light into the effect of such mutations on SETX folding and biochemical properties. Altogether, these results broaden our understanding of SETX function in gene expression and the maintenance of genome integrity and provide clues to elucidate the molecular basis of SETX-associated neurodegenerative diseases.
Modeling tissue co-regulation to estimate tissue-specific contributions to disease
Authors: Amariuta Tiffany , Siewert-Rocks Katherine , Price Alkes L. 
Published: August 2022

AbstractIntegrative analyses of genome-wide association studies (GWAS) and gene expression data across diverse tissues and cell types have enabled the identification of putative disease-critical tissues. However, co-regulation of genetic effects on gene expression across tissues makes it difficult to distinguish biologically causal tissues from tagging tissues. While previous work emphasized the potential of accounting for tissue co-regulation, tissue-specific disease effects have not previously been formally modeled. Here, we introduce a new method, tissue co-regulation score regression (TCSC), that disentangles causal tissues from tagging tissues and partitions disease heritability (or covariance) into tissue-specific components. TCSC leverages gene-disease association statistics across tissues from transcriptome-wide association studies (TWAS), which implicate both causal and tagging genes and tissues. TCSC regresses TWAS chi-square statistics (or products of z-scores) on tissue co-regulation scores reflecting correlations of predicted gene expression across genes and tissues. In simulations, TCSC distinguishes causal tissues from tagging tissues while controlling type I error. We applied TCSC to GWAS summary statistics for 78 diseases and complex traits (averageN= 302K) and gene expression prediction models for 48 GTEx tissues. TCSC identified 21 causal tissue-trait pairs at 5% FDR, including well-established findings, biologically plausible novel findings (e.g. aorta artery and glaucoma), and increased specificity of known tissue-trait associations (e.g. subcutaneous adipose, but not visceral adipose, and HDL). TCSC also identified 17 causal tissue-trait covariance pairs at 5% FDR. For the positive genetic covariance between BMI and red blood cell count, brain substantia nigra contributed positive covariance while pancreas contributed negative covariance; this suggests that genetic covariance may reflect distinct tissue-specific contributions. Overall, TCSC is a precise method for distinguishing causal tissues from tagging tissues, improving our understanding of disease and complex trait biology.
A survey of patient and public perceptions and awareness of SARS-CoV-2-related risks among participants in India and South Africa
Authors: Mbamalu Oluchi , Surendran Surya , Nampoothiri Vrinda , Bonaconsa Candice , Edathadathil Fabia , Zhu Nina , Carter Vanessa , Lambert Helen , Tarrant Carolyn , Ahmad Raheelah , Brink Adrian , Steenkamp Ebrahim , Holmes Alison , Singh Sanjeev , Charani Esmita , Mendelson Marc 
Published: August 2022

ABSTRACTA cross-sectional survey was performed among the adult population of participating countries, India and South Africa. The purpose of this study was to explore perceptions and awareness of SARS-CoV-2-related risks in the relevant countries. The main outcome measures were the proportion of participants aware of SARS-CoV-2, and their perception of infection risks.Self-administered questionnaires were used to collect data via a web- and paper-based survey over three months. For data capturing, Microsoft Excel was employed, and descriptive statistics used for presenting data. Pearson’s Chi-squared test was used to assess relationships between variables, and a p-value less than 0.05 was considered significant.There were 844 respondents (India: n=660, South Africa: n=184; response rate 87.6%), with a 61.1% vs 38.3% female to male ratio. Post-high-school or university education was the lowest qualification reported by most respondents in India (77.3%) and South Africa (79.3%). Sources of information about the pandemic were usually media and journal publications (73.2%), social media (64.6%), family and friends (47.7%) and government websites (46.2%). Most respondents correctly identified infection prevention measures (such as physical distancing, mask use), with 90.0% reporting improved hand hygiene practices since the pandemic. Hesitancy or refusal to accept the SARS-CoV-2 vaccine was reported among 17.9% and 50.9% of respondents in India and South Africa, respectively. Reasons cited included rushed vaccine development and the futility of vaccines for what respondents considered a self-limiting flu-like illness.Respondents identified public health promotion measures for SARS-CoV-2. Reported hesitancy to the up-take of SARS-CoV-2 vaccines was much higher in South Africa. Vaccination campaigns should consider robust public engagement and contextually fit communication strategies with multimodal, participatory online and offline initiatives to address public concerns, specifically towards vaccines developed for this pandemic and general vaccine hesitancy.
Effects of stimulus timing on the acquisition of an olfactory working memory task in head-fixed mice
Authors: Reuschenbach Josefine , Reinert Janine K , Fukunaga Izumi 
Published: August 2022

AbstractKnowing what factors affect the acquisition of a behavioural task is central to understanding the mechanisms of learning and memory. It also has practical implications, as animal behavioural experiments used to probe cognitive functions often require long training durations. Delayed Match (or Non-Match)-to-Sample (DMS/DNMS) tasks are relatively complex tasks used to study working memory and sensory perception, but their use in the mouse remains hampered by the lengthy training involved. In this study, we assessed two aspects of stimulus timing on the acquisition of an olfactory DNMS task: how the sample-test odour delay durations and the reward timing affect the acquisition rate. We demonstrate that head-fixed mice learn to perform an olfactory DNMS task more quickly when the initial training uses a shorter sample-test odour delay without detectable loss of generalisability. Unexpectedly, we observed a slower task acquisition when the odour-reward interval was shorter. This effect was accompanied by a shortening of reaction times and more frequent sporadic licking. Analysis of this result using a drift-diffusion model indicated that a primary consequence of early reward delivery is a lower decision bound. Since an accurate performance with a lower decision bound requires greater discriminability in the sensory representations, this may underlie the slower learning rate with early reward arrival. Together, our results reflect the possible effects of stimulus timing on stimulus encoding and its consequence on the acquisition of a complex task.
Underreported in-water behaviours of the loggerhead sea turtle:Getting buried in the sand
Authors: Papafitsoros Kostas 
Published: August 2022

AbstractIn this short report, we provide a direct evidence that loggerhead sea turtlesCaretta carettaare capable of partially burying themselves in the sand by actively moving their front flippers and stirring the sea bottom sediment. In particular, we report the cases of three male loggerhead sea turtles from Zakynthos island, Greece, which, after obtaining a resting position on a sandy spot at the sea bottom, they actively performed digging and stirring movements with their front flippers, resulting to the sand getting raised at the sea column. When the sand settled back, the turtles ended up half-buried and camouflaged. To our current knowledge, this self-burying behaviour has not been described in the literature.
Fighting isn’t sexy in lekking Greater Sage-grouse (Centrocercus urophasianus)
Authors: Snow Samuel S. , Patricelli Gail L. , Butts Carter T. , Krakauer Alan H. , Perry Anna C. , Logsdon Ryane , Prum Richard O. 
Published: August 2022

AbstractIn lekking systems, females can observe both male courtship displays and fights. It has been theorized that male-male agonism may function as a display, giving females more information about mate quality. However, males in many species, such as Greater Sage-grouse, often fight when females are absent, and can even attack during copulation attempts in seeming conflict with females’ choices.Traditional correlational approaches are inadequate to distinguish the underlying mechanisms of social interaction and can result in misleading associations between fighting and mating events. Using observations from a wild population, we posit a novel Relational Event Model that incorporates temporal dependencies of events among a network of individuals. We investigate how fighting among male sage-grouse predicts events such as future fights, copulation solicitations, and interrupted copulations.Our analysis reveals that fighting’s primary function is not to impress females. Indeed, males are less likely to start and more likely to leave fights with females present, plausibly to avoid entanglement in conflict that reduces availability to mate. Moreover, being drawn into these latter viscous cycles of combat and retribution constitutes a significant risk associated with initiating attacks on other males. However, fighting serves other roles, e.g., to deter copulation interruptions and rebuff competitors. Our findings suggest that social systems that regulate conflict and promote females’ choice based on display are likely fundamental to the stable evolution of leks.
Movement data link phenotypic traits to individual fitness in a nocturnal predator
Authors: Becciu Paolo , Séchaud Robin , Schalcher Kim , Plancherel Céline , Roulin Alexandre 
Published: August 2022

AbstractRecent biologging technology reveals hidden life and breeding strategies of nocturnal animals. Combining animal movement patterns with individual characteristics and landscape features can uncover meaningful behaviours that directly influence fitness. Consequently, defining the proximate mechanisms and adaptive value of the identified behaviours is of paramount importance. Breeding female barn owls (Tyto alba), a colour-polymorphic species, recurrently visit other nest boxes at night. We described and quantified this behaviour for the first time, linking it with possible drivers, and individual fitness. We GPS-equipped 178 breeding pairs of barn owls from 2016 to 2020 in western Switzerland during the chick rearing phase. We observed that 65% of breeding females tracked were (re)visiting nest boxes while still carrying out their first brood. We modelled their prospecting parameters as a function of partner-, individual- and brood-related variables, and found that female feather eumelanism predicted the emergence of prospecting behaviour (less melanic females are usually prospecting), while increasing male parental investment increased female exploratory efforts. Ultimately, females would revisit a nest more often if they had used it in the past and were more likely to lay a second clutch afterwards, consequently having higher annual fecundity than non-prospecting females. Despite these apparent immediate benefits, they did not fledge more chicks. We highlight how phenotypic traits can be related to movement patterns and individual fitness through biologging associated with long-term field monitoring.
Dynamic modelling and analysis of autophagy in the clearance of aggregated α-synuclein in Parkinson’s disease
Authors: Yang Bojie , Yang Zhuoqin , Liu Heng 
Published: August 2022

AbstractThe widely-accepted hallmark pathology of Parkinson’s disease (PD) is the presence of Lewy bodies (LB) with characteristic abnormal aggregated α-synuclein (αSyn). Growing physiological evidences suggest that there is a pivotal role for the autophagy-lysosome pathway in the clearance of misfolded αSyn (αSyn*) for maintaining homeostasis and neural cell function. In this work, we establish a new mathematical model for αSyn* degradation through the autophagy pathway. The qualitative simulations discover the tri-stability phenomena and dynamical behaviors of αSyn*, i.e., the coexistence of three stable steady states, in which the lower, medium and upper steady states correspond to the healthy, critical and diseased stages of pathological mechanism of PD, respectively. Diverse analyses on codimension-1 and -2 bifurcations suggest that autophagy can control the switches among the stable steady states for the aggregation of αSyn*. It is also found that the double negative crosstalk feedback between autophagy and apoptosis is important to the robustness of tri-stability of αSyn* for this biodynamic system. Our novel results may be valuable for making further therapeutic strategies in prevention and treatment for PD.Author summaryαSyn* is one of the most and primary remarkable targets for the universal neurodegenerative disease of PD. Efficient clearance mechanism of autophagy, contains a lot of molecular components to maintain the cellular homeostasis and cell renewal, could be the possible therapy for PD. Understand the complexity of autophagy in degrading αSyn* requires the integration of both theoretical and experimental points of view. Here, we have proposed a novel mathematical model that analyses the temporal and dynamic behaviors of the biosystem for autophagy degrades αSyn* to access PD states. The model explains that the tri-stability is of particularly relevance to this biosystem that switch among the healthy, critical and disease states, and captures that the critical intermedium state exits for preventing the system transform healthy to disease state directly, and further illustrates that the molecular signaling feedback loops of autophagy may be important for the robustness of tri-stability. Our work deepens the researches of PD by uncovering the important buffering medium state and providing promising potential therapeutic insights.
Myosin-dependent partitioning of junctional Prickle2 toward the anterior vertex during planar polarization of Xenopus neuroectoderm
Authors: Chu Chih-Wen , Davidson Lance A. 
Published: August 2022

AbstractPlanar cell polarity (PCP) of tissues is established by mutually exclusive partitioning of transmembrane proteins Frizzled and Vangl with their respective binding partners, Dishevelled and Prickle. While the amplification and maintenance of this pattern have been well studied, it remains unclear how the anterior-biased protein localization is initiated. Moreover, PCP protein complexes are located at adherens junctions and their polarization requires the activity of non-muscle myosin II (NMII), but how NMII contributes to PCP is not fully understood. Here we analyze time-lapse images of mNeonGreen-tagged Prickle2 (Pk2) in mid-gastrula stage Xenopus presumptive neuroectoderm and demonstrate that Pk2 puncta move along bicellular apical junctions in a biased manner toward the anterior vertex, where the Vangl-Pk complexes are normally enriched. In addition, length changes of bicellular junction segments flanking each Pk2 punctum are often different from each other, and appear more dynamic near the vertices, suggesting that Pk2 movement is driven by intrinsic junction heterogeneity. Reducing NMII activity eliminates the anterior movement, and surprisingly, increases the motility of Pk2 punta. By assessing the correlation between Pk2 movement and the relative positioning of each Pk2 punctum along apical junctions, we uncovered that NMII activity is required for the anterior Pk2 movement by maintaining the elongation of posterior junction segment while inhibiting Pk2 movement toward both vertices flanking the junctions. Our findings provide the first evidence of biased partitioning of junctional PCP proteins toward the anterior vertex and support the hypothesis that NMII activity facilitates Pk2 polarization not via a direct transport but by regulating intrinsic dynamics of the bicellular junction.
Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients
Authors: Becker Heike E.F. , Kameli Nader , Rustichelli Alice , Heijnens Britt A.M. , Stassen Frank , Penders John , Jonkers Daisy M.A.E. 
Published: August 2022

AbstractBackgroundCrohn’s disease (CD) is a chronic inflammatory gastro-intestinal condition with variable disease course. Impaired barrier function and microbial dysbiosis are associated with disease onset and exacerbations. We hypothesized that perturbed microbial activity may contribute to the impaired barrier function in CD. Therefore, this study aimed to examine the impact of faecal bacterial products of active and remissive CD patients, and healthy controls (HC) on mucin degradation and epithelial barrier function in vitro.MethodsSix HC and twelve CD patients were included. Disease activity was determined by endoscopy. Fecal water (FW) and bacterial membrane vesicles (MVs) from fresh fecal samples were applied on mucin agar to determine mucin degradation and on differentiated Caco-2 cell monolayers to assess transepithelial electrical resistance (TEER) and paracellular junction stability. Relative abundances of fecal bacterial genera, which may be associated mucin degradation, were evaluated using 16S rRNA gene amplicon sequencing.ResultsFW-induced mucin degradation was higher in CD samples as compared to HC (p<0.01), but was not linked to specific bacterial relative abundances. FW resulted in 78-87% decrease of TEER in three of the remissive (p<0.001) but not the active CD or HC samples. MVs did not induce mucin degradation or epithelial barrier disruption.ConclusionThe higher mucin degradation capacity of CD-derived FW might indicate contributions of microbial products to CD pathophysiology and warrants further investigation. Moreover, the altered epithelial resistance in some individuals is not due to paracellular disruption.Key MessagesWhat is already known? Intestinal microbial dysbiosis and mucosal barrier dysfunction are important contributors to Crohn’s disease aetiology and disease exacerbations.What is new here? The faecal microbial secretome of Crohn’s disease patients has a higher mucin degradation capacity as compared to the secretome of healthy subjects.How can this study help patient care? The increased mucin degradation based on the microbial secretome may be a new target for the development of complementary, microbiome-based therapy in Crohn’s disease.SummaryMicrobial dysbiosis and intestinal barrier dysfunction can impact Crohn’s disease course. This translational study found higher mucin degradation, but no epithelial barrier disruption, by the faecal microbial secretome of (active) Crohn’s disease patients, as compared to healthy controls.