bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of fruiting rather than topography determines the direction of vertical seed dispersal by mammals and birds
Authors: Tsunamoto Y. , Koike S. , Tayasu I. , Masaki T. , Kato S. , Kikuchi S. , Nagamitsu T. , Haraguchi T. , Naganuma T. , Naoe S. 
Published: May 2020

ABSTRACTVertical seed dispersal toward higher or lower altitudes has been recognized as one of the critical processes for plants to escape from climate change. Studies exploring vertical seed dispersal are scarce, preventing the prediction of future vegetation dynamics. In the present study, we show that the timing of fruiting, rather than topography, determines the direction of vertical seed dispersal by mammals and birds across mountains in central Japan. We found strong uphill seed dispersal of summer fruiting cherry and weak downhill seed dispersal of summer-to-autumn fruiting cherry, irrespective of mountains and animals. The ascent or descent of animals, following the altitudinal gradients in food plant phenology in the temperate zone, was considered to be a driver of the biased seed dispersal. We found that megafauna (i.e., bears) intensively dispersed seeds vertically. The results suggest that the timing of fruiting and megafauna strongly affect whether animal-dispersed temperate plants can maintain their populations under climate change.
Emergence and Propagation of Epistasis in Metabolic Networks
Authors: Kryazhimskiy Sergey 
Published: May 2020

AbstractEpistasis is often used to probe functional relationships between genes, and it plays an important role in evolution. However, we lack theory to understand how functional relationships at the molecular level translate into epistasis at the level of whole-organism phenotypes, such as fitness. Here, I derive two rules for how epistasis between mutations with small effects propagates from lower-to higher-level phenotypes in a hierarchical metabolic network with first-order kinetics and how such epistasis depends on topology. Most importantly, weak epistasis at a lower level may be distorted as it propagates to higher levels. Computational analyses show that epistasis in more realistic models likely follows similar, albeit more complex, patterns. These results suggest that pairwise inter-gene epistasis should be common and it should generically depend on the genetic background and environment. Furthermore, the epistasis coefficients measured for high-level phenotypes may not be sufficient to fully infer the underlying functional relationships.
Social structure defines spatial transmission of African swine fever in wild boar
Authors: Pepin Kim M. , Golnar Andrew , Podgórski Tomasz 
Published: May 2020

AbstractSpatial spread of infectious disease is determined by spatial and social processes such as animal space use and family group structure. Yet, impacts of social processes on spatial spread remain poorly understood and estimates of spatial transmission kernels (STKs) often exclude social structure. Understanding impacts of social structure on STKs is important for obtaining robust inferences for policy decisions and optimizing response plans.We fit spatially-explicit transmission models with different assumptions about contact structure to African swine fever virus (ASFv) surveillance data from Eastern Poland from 2014-2015 and evaluated how social structure affected inference of STKs and spatial spread.The model with social structure provided better inference of spatial spread, predicted that ∼80% of transmission events occurred within family groups, and that transmission was weakly female-biased (other models predicted weakly male-biased transmission). In all models, most transmission events were within 1.5 km, with some rare events at longer distances. Effective reproductive numbers were between 1.1 and 2.5 (maximum values between 4 and 8).Social structure can modify spatial transmission dynamics. Accounting for this additional contact heterogeneity in spatial transmission models could provide more robust inferences of STKs for policy decisions, identify best control targets, and improve transparency in model uncertainty.
Inferring TF activities and activity regulators from gene expression data with constraints from TF perturbation data
Authors: Ma Cynthia , Brent Michael R. 
Published: May 2020

ABSTRACTBackgroundThe activity of a transcription factor (TF) in a sample of cells is the extent to which it is exerting its regulatory potential. Many methods of inferring TF activity from gene expression data have been described, but due to the lack of appropriate large-scale datasets, systematic and objective validation has not been possible until now.ResultsUsing a new dataset, we systematically evaluate and optimize the approach to TF activity inference in which a gene expression matrix is factored into a condition-independent matrix of control strengths and a condition-dependent matrix of TF activity levels. These approaches require a TF network map, which specifies the target genes of each TF, as input. We evaluate different approaches to building the network map and deriving constraints on the matrices. We find that such constraints are essential for good performance. Constraints can be obtained from expression data in which the activities of individual TFs have been perturbed, and we find that such data are both necessary and sufficient for obtaining good performance. Remaining uncertainty about whether a TF activates or represses a target is a major source of error. To a considerable extent, control strengths inferred using expression data from one growth condition carry over to other conditions. As a result, the control strength matrices derived here can be used for other applications. Finally, we apply these methods to gain insight into the upstream factors that regulate the activities of four yeast TFs: Gcr2, Gln3, Gcn4, and Msn2. Evaluation code and data available athttps://github.com/BrentLab/TFA-evaluationConclusionsWhen a high-quality network map, constraints, and perturbation-response data are available, inferring TF activity levels by factoring gene expression matrices is effective. Furthermore, it provides insight into regulators of TF activity.
“Temporal control of tumor growth in nocturnal mammals: impact of the circadian system”
Authors: Wagner Paula M. , Prucca César G. , Velázquez Fabiola N. , Alderete Lucas Sosa , Caputto Beatriz L. , Guido Mario E. 
Published: May 2020

AbstractGlioblastoma multiforme is the most aggressive brain tumor; however, little is known about the impact of the circadian system on the tumor formation, growth and treatment. We investigated day/night differences in tumor growth after injecting A530 glioma cells isolated from malignant peripheral nerve sheath tumor of NPcis (Trp53+/-;Nf1+/-)mice. Tumors generated in the sciatic nerve zone of C57BL/6 mice injected early at night in the light/dark cycle or in constant darkness, showed higher growth rates than in animals injected diurnally. Similar nocturnal increases were observed when injecting B16 melanoma cells or when mice received knocked-down clock geneBmal1 cells. Moreover, treatment with a low-dose of the proteasome inhibitor Bortezomib (0.5 mg/kg) in tumor-bearing animals, displayed higher efficacy when administered at night. Results suggest the existence of a precise temporal control of tumor growth and of drug efficacy in which the host state and susceptibility are critical.
Collective protection and transport in entangled biological and robotic active matter
Authors: Ozkan-Aydin Yasemin , Goldman Daniel I. , Bhamla M. Saad 
Published: May 2020

Living systems at all scales aggregate in large numbers for a variety of functions including mating, predation, and survival. The majority of such systems consist of unconnected individuals that collectively flock, school or swarm. However some aggregations involve physically entangled individuals, which can confer emergent mechanofunctional material properties to the collective. Here we study in laboratory experiments and rationalize in theoretical and robotic models the dynamics of physically entangled and motile self-assemblies of centimeter long California blackworms (L. Variegatus). Thousands of individual worms form braids with their long, slender and flexible bodies to make a three-dimensional, soft and shape-shifting ‘blob’. The blob behaves as a living material capable of mitigating damage and assault from environmental stresses through dynamic shape transformations, including minimizing surface area for survival against desiccation and enabling transport (negative thermotaxis) from hazardous environments (like heat). We specifically focus on the locomotion of the blob to understand how an amorphous entangled ball of worms is able to break symmetry to move across a substrate. We hypothesize that the collective blob displays rudimentary differentiation of function across itself, which when combined with entanglement dynamics facilitates directed persistent blob locomotion. To test this, we develop robophysical blobs, which display emergent locomotion in the collective without sophisticated control or programming of any individual robot. The emergent dynamics of the living functional blob and robophysical model can inform the rational design of exciting new classes of adaptive mechanofunctional living materials and emergent swarm robotics.Significance StatementLiving organisms form collectives across all scales, from bacteria to whales, enabling biological functions not accessible by individuals alone. In a few small cases, the individuals are physically connected to each other, forming to a new class of entangled active matter systems with emergent mechanofunctionalities of the collective. Here, we describe the dynamics of macroscopic aquatic worms that braid their long, soft bodies to form large entangled worm blobs. We discover that the worm blob behaves as a living material to undergo dynamic shape transformations to reduce evaporation or break-symmetry and locomote to safety against thermal stresses. We show that the persistent blob locomotion emerges as a consequence of physical entanglement and functional differentiation of individuals based on spatial location within a blob. We validate these principles in robophysical swarming blobs, that pave the way for new classes of mechanofunctional active matter systems and collective emergent robotics.
Differential risk for COVID-19 in the first wave of the disease (February-April 2020) among migrants from several areas of the world living in Alcorcón (Spain): A population-based cohort study
Authors: Guijarro Carlos , Pérez-Fernández Elia , González-Piñeiro Beatriz , Meléndez Victoria , Goyanes Maria José , Renilla Ma Esther , Casas Maria Luisa , Sastre Isabel , Velasco María ,   Alcorcon COVID Investigators.
Published: May 2020

AbstractLittle is known regarding the relevance of racial / ethnic background on the risk of COVID-IO infection, particularly in Europe. We evaluated the risk for COVID-19 among migrants from different areas of the world within a context of universal free access to medical care. We conducted a population-based cohort analysis of the cumulative incidence of PCR-confirmed COVID-19 among adult residents at Alcorcón (Spain) in the first wave of the disease. The crude cumulative incidence among migrants (n=20419) was higher than among Spaniards (n=131599): 8.81 and 6.51 and per 1000 inhabitants respectively (p<0.001) but differed by world region of origin. By negative binomial regression, adjusted for age and sex, relative risks (RR) for COVID-19 were not significantly different from Spaniards for individuals from Europe, Asia or Northern Africa. In contrast, there was a marked increased risk for Sub-Saharan Africa (RR 3.66, 95% confidence interval (Cl) 42-9.41, p=0.007), Caribbean (RR6.35, 95% Cl 3.83-10.55, p<0.001) and Latin-America (RR6.92, 95% Cl 4.49-10.67, p <0.001). Migrants from these areas of the world may deserve a closer attention both for clinical and epidemiological reasons.
Association of the Covid-19 lockdown with smoking, drinking, and attempts to quit in England: an analysis of 2019-2020 data
Authors: Jackson Sarah E. , Garnett Claire , Shahab Lion , Oldham Melissa , Brown Jamie 
Published: May 2020

AbstractAimTo examine changes in smoking, drinking, and quitting/reduction behaviour following the Covid-19 lockdown in England.Design/settingMonthly cross-sectional surveys representative of the adult population in England, aggregated before (April 2019 through February 2020) versus after (April 2020) the lockdown.Participants20,558 adults (≥16y).MeasurementsThe independent variable was the timing of the Covid-19 lockdown in England (before vs. after March 2020). Dependent variables were: prevalence of smoking and high-risk drinking; past-year cessation and quit attempts (among past-year smokers); past-year attempts to reduce alcohol consumption (among high-risk drinkers); and use of evidence-based (e.g., prescription medication/face-to-face behavioural support) and remote support (telephone support/websites/apps) for smoking cessation and alcohol reduction (among smokers/high-risk drinkers who made a quit/reduction attempt). Covariates included age, sex, social grade, region, and level of nicotine and alcohol dependence (as relevant).FindingsThe Covid-19 lockdown was not associated with a significant change in smoking prevalence (17.0% (after) vs. 15.9% (before), C)R=1.09[95%CI 0.95-1.24]), but was associated with increases in the rate of quit attempts (39.6% vs. 29.1%, ORadj=1.56[l.23-1.98]) and cessation (8.8% vs. 4.1%, ORadj=2.63[1.69-4.09]) among past-year smokers. Among smokers who tried to quit, there was no significant change in use of evidence-based support (50.0% vs. 51.5%, ORadj=1.10[0.72-1.68]) but use of remote support increased (10.9% vs. 2.7%, ORadj=3.59[1.56-8.23]). Lockdown was associated with increases in the prevalence of high-risk drinking (38.3% vs. 25.1%, OR=1.85[1.67-2.06]) but also alcohol reduction attempts by high-risk drinkers (28.5% vs. 15.3%, ORadr2.16[1.77-2.64]). Among high-risk drinkers who made a reduction attempt, use of evidence-based support decreased (1.2% vs. 4.0%, ORadj=0.23[0.05-0.97]) and there was no significant change in use of remote support (6.9% vs. 6.1%, ORadj=1.32[0.64-2.75]).ConclusionsIn England, prevalence of high-risk drinking but not smoking has increased since the Covid-19 lockdown. Smokers and high-risk drinkers are more likely than before lockdown to report trying to quit smoking or reduce their alcohol consumption, and rates of smoking cessation are higher. Smokers are no less likely than before lockdown to use cessation support, with increased uptake of remote support. However, use of evidence-based support for alcohol reduction by high-risk drinkers has decreased, with no compensatory increase in use of remote support.
A chest radiography-based artificial intelligence deep-learning model to predict severe Covid-19 patient outcomes: the CAPE (Covid-19 AI Predictive Engine) Model
Authors: Liew Charlene , Quah Jessica , Goh Han Leong , Venkataraman Narayan 
Published: May 2020

AbstractBackgroundChest radiography may be used together with deep-learning models to prognosticate COVID-19 patient outcomesPurposeT o evaluate the performance of a deep-learning model for the prediction of severe patient outcomes from COVID-19 pneumonia on chest radiographs.MethodsA deep-learning model (CAPE: Covid-19 AI Predictive Engine) was trained on 2337 CXR images including 2103 used only for validation while training. The prospective test set consisted of CXR images (n=70) obtained from RT-PCR confirmed COVID-19 pneumonia patients between 1 January and 30 April 2020 in a single center. The radiographs were analyzed by the AI model. Model performance was obtained by receiver operating characteristic curve analysis.ResultsIn the prospective test set, the mean age of the patients was 46 (+/-16.2) years (84.2% male). The deep-learning model accurately predicted outcomes of ICU admission/mortality from COVID-19 pneumonia with an AUC of 0.79 (95% CI 0.79-0.96). Compared to traditional risk scoring systems for pneumonia based upon laboratory and clinical parameters, the model matched the EWS and MulBTSA risk scoring systems and outperformed CURB-65.ConclusionsA deep-learning model was able to predict severe patient outcomes (ICU admission and mortality) from COVID-19 on chest radiographs.Key ResultsA deep-learning model was able to predict severe patient outcomes (ICU admission and mortality) from COVID-19 from chest radiographs with an AUC of 0.79, which is comparable to traditional risk scoring systems for pneumonia.Summary StatementThis is a chest radiography-based AI model to prognosticate the risk of severe COVID-19 pneumonia outcomes.
Rala and the exocyst control Pvr trafficking and signaling to ensure lymph gland homeostasis inDrosophila melanogaster
Authors: Knævelsrud Helene , Baril Caroline , Gavory Gwenaëlle , Enserink Jorrit M. , Therrien Marc 
Published: May 2020

AbstractThe balance between hematopoietic progenitors and differentiated hemocytes is finely tuned during development. In the larval hematopoietic organ ofDrosophila, called the lymph gland, the receptor tyrosine kinase Pvr signals from differentiated cells to maintain a pool of undifferentiated progenitors. However, little is known about the processes that support Pvr function. The small GTPase Ral is involved in the regulation of several membrane trafficking events.Drosophilahas a single Ral protein, Rala, which has been implicated in the development of various tissues. Here, we investigated the involvement of Rala in the larval fly hematopoietic system. We discovered that the loss ofRalaactivity phenocopiesPvrloss of function by promoting hemocyte progenitor differentiation. Moreover, using epistasis analysis, we found that the guanine exchange factor RalGPS lies upstream of Rala in this event, whereas the exocyst and Rab11 are acting downstream. Strikingly, the loss of Rala activity leads to a considerable accumulation of Pvr at the plasma membrane, hence suggesting a trafficking defect and reduced Pvr function. Consistent with this hypothesis,Ralaloss of function phenotype in the lymph gland is fully suppressed by constitutive STAT activity, which normally mediates Pvr function in the lymph gland. Together, our findings unravel a novel RalGPS-Rala-exocyst-Rab11 axis for the maintenance of lymph gland homeostasis through Pvr.
PelX is a UDP-N-acetylglucosamine C4-epimerase involved in Pel polysaccharide-dependent biofilm formation
Authors: Marmont Lindsey S. , Whitfield Gregory B. , Pfoh Roland , Williams Rohan J. , Randall Trevor E. , Ostaszewski Alexandra , Razvi Erum , Groves Ryan A. , Robinson Howard , Nitz Mark , Parsek Matthew R. , Lewis Ian A. , Whitney John C. , Harrison Joe J. , Howell P. Lynne 
Published: May 2020

ABSTRACTPel is anN-acetylgalactosamine rich polysaccharide that contributes to the structure and function ofPseudomonas aeruginosabiofilms. ThepelABCDEFGoperon is highly conserved among diverse bacterial species, and thus Pel may be a widespread biofilm determinant. Previous annotation ofpelgene clusters led us to identify an additional gene,pelX, that is found adjacent topelABCDEFGin over 100 different bacterial species. ThepelXgene is predicted to encode a member of the short-chain dehydrogenase/reductase (SDR) superfamily of enzymes, but its potential role in Pel-dependent biofilm formation is unknown. Herein, we have usedPseudomonas protegensPf-5 as a model to understand PelX function asP. aeruginosalacks apelXhomologue in itspelgene cluster. We find thatP. protegensforms Pel-dependent biofilms, however, despite expression ofpelXunder these conditions, biofilm formation was unaffected in a ΔpelXstrain. This observation led to our identification of thepelXparalogue, PFL_5533, which we designatepgnE, that appears to be functionally redundant topelX. In line with this, a ΔpelXΔpgnEdouble mutant was substantially impaired in its ability to form Pel-dependent biofilms. To understand the molecular basis for this observation, we determined the structure of PelX to 2.1Å resolution. The structure revealed that PelX resembles UDP-N-acetylglucosamine (UDP-GlcNAc) C4-epimerases and, using1H NMR analysis, we show that PelX catalyzes the epimerization between UDP-GlcNAc and UDP-GalNAc. Taken together, our results demonstrate that Pel-dependent biofilm formation requires a UDP-GlcNAc C4-epimerase that generates the UDP-GalNAc precursors required by the Pel synthase machinery for polymer production.
An updated staging system for cephalochordate development: one table suits them all
Authors: Carvalho João E. , Lahaye François , Yong Luok Wen , Croce Jenifer C. , Escrivá Hector , Yu Jr-Kai , Schubert Michael 
Published: May 2020

AbstractChordates are divided into three subphyla: Vertebrata, Tunicata and Cephalochordata. Phylogenetically, the Cephalochordata, more commonly known as lancelets or amphioxus, constitute the sister group of Vertebrata and Tunicata. Lancelets are small, benthic, marine filter feeders, and their roughly three dozen described species are divided into three genera:Branchiostoma,EpigonichthysandAsymmetron. Due to their phylogenetic position and their stereotypical chordate morphology and genome architecture, lancelets are key models for understanding the evolutionary history of chordates. Lancelets have thus been studied by generations of scientists, with the first descriptions of adult anatomy and developmental morphology dating back to the 19thcentury. Today, several different lancelet species are used as laboratory models, predominantly for developmental, molecular and genomic studies. Surprisingly, however, a universal staging system and an unambiguous nomenclature for developing lancelets have not yet been adopted by the scientific community.In this work, we characterized the development of the European amphioxus (Branchiostoma lanceolatum) using confocal microscopy and compiled a streamlined developmental staging system, from fertilization through larval life, including an unambiguous stage nomenclature. By tracing growth curves of the European amphioxus reared at different temperatures, we were able to show that our staging system permitted an easy conversion of any developmental time into a specific stage name. Furthermore, comparisons of embryos and larvae from the European lancelet (B. lanceolatum), the Florida lancelet (B. floridae), the Chinese lancelet (B. belcheri), the Japanese lancelet (B. japonicum) and the Bahamas lancelet (Asymmetron lucayanum) demonstrated that our staging system could readily be applied to other lancelet species.Although the detailed staging description was carried out on developingB. lanceolatum, the comparisons with other lancelet species thus strongly suggested that both staging and nomenclature are applicable to all extant lancelets. We conclude that this description of embryonic and larval development will be of great use for the scientific community and that it should be adopted as the new standard for defining and naming developing lancelets. More generally, we anticipate that this work will facilitate future studies comparing representatives from different chordate lineages.