bluuebunny/crossref_metadata_2025_split huggingface dataset:
The landscape of alternative polyadenylation in single cells of the developing mouse embryo
Authors: Agarwal Vikram , Lopez-Darwin Sereno , Kelley David R. , Shendure Jay 
Published: January 2021

ABSTRACT3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examined a dataset comprising ∼2 million cells spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RBP dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.
Quantifying cell transitions inC. eleganswith data-fitted landscape models
Authors: Camacho-Aguilar Elena , Warmflash Aryeh , Rand David A. 
Published: January 2021

AbstractIncreasing interest has emerged in new mathematical approaches that simplify the study of complex differentiation processes by formalizing Waddington’s landscape metaphor. However, a rational method to build these landscape models remains an open problem. Building on pioneering work byCorson and Siggia(2012, 2017) we study vulval development inC. elegansby developing a framework based on Catastrophe Theory (CT) and approximate Bayesian computation (ABC) to build data-fitted landscape models. We first identify the candidate qualitative landscapes, and then use CT to build the simplest model consistent with the data, which we quantitatively fit using ABC. The resulting model suggests that the underlying mechanism is a quantifiable two-step decision controlled by EGF and Notch-Delta signals, where a non-vulval/vulval decision is followed by a bistable transition to the two vulval states. This new model fits a broad set of data and makes several novel predictions.
Evolution of recombination landscapes in diverging populations of bread wheat
Authors: Danguy des Déserts Alice , Bouchet Sophie , Sourdille Pierre , Servin Bertrand 
Published: January 2021

AbstractReciprocal exchanges of DNA (crossovers) that occur during meiosis are mandatory to ensure the production of fertile gametes in sexually reproducing species. They also contribute to shuffle parental alleles into new combinations thereby fuelling genetic variation and evolution. However, due to biological constraints, the recombination landscape is highly heterogenous along the genome which limits the range of allelic combinations and the adaptability of populations. An approach to better understand the constraints on the recombination process is to study how it evolved in the past. In this work we tackled this question by constructing recombination profiles in four diverging bread wheat (Triticum aestivum L.) populations established from 371 landraces genotyped at 200,062 SNPs. We used linkage disequilibrium (LD) patterns to estimate in each population the past distribution of recombination along the genome and characterize its fine-scale heterogeneity. At the megabase scale, recombination rates derived from LD patterns were consistent with family-based estimates obtained from a population of 406 recombinant inbred lines. Among the four populations, recombination landscapes were significantly positively correlated between each other and shared a statistically significant proportion of highly recombinant intervals. However, this comparison also highlighted that the similarity in recombination landscapes between populations was significantly decreasing with their genetic differentiation in most regions of the genome. This observation was found to be robust to SNP ascertainment and demography and suggests a relatively rapid evolution of factors determining the fine-scale localization of recombination in bread wheat.
Brain Connectivity meets Reservoir Computing
Authors: Damicelli Fabrizio , Hilgetag Claus C. , Goulas Alexandros 
Published: January 2021

AbstractThe connectivity of Artificial Neural Networks (ANNs) is different from the one observed in Biological Neural Networks (BNNs). Can the wiring of actual brains help improve ANNs architectures? Can we learn from ANNs about what network features support computation in the brain when solving a task?ANNs’ architectures are carefully engineered and have crucial importance in many recent performance improvements. On the other hand, BNNs’ exhibit complex emergent connectivity patterns. At the individual level, BNNs connectivity results from brain development and plasticity processes, while at the species level, adaptive reconfigurations during evolution also play a major role shaping connectivity.Ubiquitous features of brain connectivity have been identified in recent years, but their role in the brain’s ability to perform concrete computations remains poorly understood. Computational neuroscience studies reveal the influence of specific brain connectivity features only on abstract dynamical properties, although the implications of real brain networks topologies on machine learning or cognitive tasks have been barely explored.Here we present a cross-species study with a hybrid approach integrating real brain connectomes and Bio-Echo State Networks, which we use to solve concrete memory tasks, allowing us to probe the potential computational implications of real brain connectivity patterns on task solving.We find results consistent across species and tasks, showing that biologically inspired networks perform as well as classical echo state networks, provided a minimum level of randomness and diversity of connections is allowed. We also present a framework,bio2art, to map and scale up real connectomes that can be integrated into recurrent ANNs. This approach also allows us to show the crucial importance of the diversity of interareal connectivity patterns, stressing the importance of stochastic processes determining neural networks connectivity in general.
A duplicated copy of the meiotic geneZIP4preserves up to 50% pollen viability and grain number in polyploid wheat
Authors: Alabdullah Abdul Kader , Moore Graham , Martín Azahara C. 
Published: January 2021

SummaryAlthough most flowering plants are polyploid, little is known of how the meiotic process evolved to stabilise and preserve polyploid fertility. On wheat polyploidisation, the major meiotic geneZIP4on chromosome 3B duplicated onto 5B and subsequently diverged. This 5B meiotic gene copy (TaZIP4-B2) was recently shown to promote homologous pairing, synapsis and crossover, and suppress homoeologous crossover. We therefore suspected that these stabilising effects on meiosis could be important for the preservation of wheat polyploid fertility.A CRISPRTazip4-B2mutant was exploited to assess the contribution of the 5B duplicatedZIP4copy in maintaining pollen viability and grain setting.Analysis demonstrated abnormalities in 56% of meiocytes in theTazip4-B2mutant, with micronuclei in 50% of tetrads, reduced size in 48% of pollen grains and a near 50% reduction in grain number. Further studies showed that most of the reduced grain number resulted from pollination with less viable pollen, suggesting that the stabilising effect ofTaZIP4-B2on meiosis has a greater consequence in subsequent male, rather than female gametogenesis.These studies reveal the extraordinary value of the wheat chromosome 5BTaZIP4-B2duplication to agriculture and human nutrition. Future studies should assess whether differentTaZIP4-B2alleles exhibit variable effects on meiotic stabilisation and/or resistance to temperature change.
Exploring the natural origins of SARS-CoV-2 in the light of recombination
Authors: Lytras Spyros , Hughes Joseph , Martin Darren , de Klerk Arné , Lourens Rentia , Kosakovsky Pond Sergei L , Xia Wei , Jiang Xiaowei , Robertson David L 
Published: January 2021

SummaryThe lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (Sarbecoviruses) have been identified, is fuelling speculation on the natural origins of SARS-CoV-2. We have comprehensively analysed phylogenetic relations between SARS-CoV-2, and the related bat and pangolin Sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Clustering of the inferred recombination events is non-random with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift in the ancestry of bat Sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm horseshoe bats, Rhinolophus, are the likely SARS-CoV-2 progenitor reservoir species. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and co-circulation of these viruses’ ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years or so. We confirm that a direct proximal ancestor to SARS-CoV-2 is yet to be sampled, since the closest relative shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for more wildlife sampling to (i) pinpoint the exact origins of SARS-CoV-2’s animal progenitor, and (ii) survey the extent of the diversity in the related Sarbecoviruses’ phylogeny that present high risk for future spillover.HighlightsThe origin of SARS-CoV-2 can be traced to horseshoe bats, genus Rhinolophus, with ranges in both China and Southeast Asia.The closest known relatives of SARS-CoV-2 exhibit frequent transmission among their Rhinolophus host species.Sarbecoviruses have undergone extensive recombination throughout their evolutionary history.Accounting for the mosaic patterns of these recombinants is important when inferring relatedness to SARS-CoV-2.Breakpoint patterns are consistent with recombination hotspots in the coronavirus genome, particularly upstream of the pike open reading frame with a coldspot in S1.
Working mechanism and experimental study of electromagnetic measurement while drilling systems based on a relay station
Authors: Lu Chunhua , Wang Rongjing , Zhao Huibin , Zhang Tao 
Published: January 2021

ABSTRACTElectromagnetic measurement while drilling systems transmit downhole data via an information channel composed of a drill string and formation; the formation has a strong attenuation effect on the signal. Signal attenuation during electromagnetic wave transmission through the formation limits the well depth at which this technique can be applied. This paper discusses several commonly used methods to improve the depth at which electromagnetic measurement while drilling applications can be conducted, including turbine power supplies, adaptive power outputs and transmitting antenna extensions. Based on both theory and practice, the characteristics of these methods are analysed, and a relay station‐infused electromagnetic measurement while drilling system is proposed. The relay station‐infused electromagnetic measurement while drilling system consists of a downhole instrument assembly, a relay station and a ground receiver assembly. The repeater receives the electromagnetic wave signal from the underground transmitter and, after amplification, decoding and other processing, re‐encodes the signal and forwards it to the ground receiver at different frequencies, so as to increase the underground electromagnetic wave signal relay transmission. The design of the relay station module is introduced in detail, and the influencing factors and rules of signal transmission are analysed. Signal transmission experiments show that the electromagnetic measurement while drilling system based on a relay station can reliably represent the relay of signals and can thus be used in deeper wells.
Effects of 38 years of wildfires on tree density in the Blue Mountains, Australia
Authors: Rahmani Simin , Price Owen 
Published: January 2021

AbstractForests are vital for biodiversity, carbon storage and ecosystem services, but can be potentially threatened by fires. Given the significance of forests and fire in a changing climate, research into the long‐term effects of fire on forests plays an important role in understanding the global carbon cycle by the forests functioning as a large terrestrial carbon sink or source. In this study, we used aerial photography from 1975 and 2013 to count the change in the number of trees in 560 dry sclerophyll plots (40 × 40m) in the Blue Mountains of Australia. We analysed the relationship between the number of fires and severe fires in that period on the change in numbers of trees. We found that the average response was an increase of 1 tree per plot over 38 years. The number of fires had a small positive effect on tree numbers; plots with 2 or 3 severe fires had 1 and 2 extra trees, respectively, than those without fire. One exception was a severe fire in 2001 that did not show this positive effect, probably because it corresponded with extensive drought. Our findings suggest that number of forest canopy trees is resilient to the number of fires and number of severe fires.
Widespread dieback in a foundation species on a sub‐Antarctic World Heritage Island: Fine‐scale patterns and likely drivers
Authors: Dickson Catherine R. , Baker David J. , Bergstrom Dana M. , Brookes Rowan H. , Whinam Jennie , McGeoch Melodie A. 
Published: January 2021

AbstractUnder anthropogenic climate change, emerging diseases and pathogens are increasingly prevalent in high latitude and altitude regions that were previously protected by cold winter temperatures. Ongoing island‐wide dieback of a foundation species, the cushion plant Azorella macquariensis, on World Heritage listed Macquarie Island provides the first sub‐Antarctic example. To better understand the island‐wide progression of cushion dieback and its drivers, we established and quantified plant condition classes and measured microclimate across 62 sites. We then tested whether the drivers of cushion dieback were associated with (i) water stress: represented by vapour pressure deficit, wind exposure and gravel content, (ii) pathogen virulence: using freezing days and extreme humidity as empirically supported surrogates, or (iii) both. There was a strong north‐south progression in cushion condition, with dieback most active in the centre of the island and advanced in the north. Dieback was most extensive at sites with fewer freezing days and high humidity. Natural southern refugia were explained by the significantly colder temperatures, associated with a north‐south temperature gradient. It is expected that under current climate change trajectories, where Macquarie is likely to continue to become warmer and wetter, cushion dieback will remain pervasive, expanding most slowly in the south and potentially outpacing recovery. We emphasise the need for increased awareness to prevent the establishment of pathogens into and across the landscapes of newly susceptible high latitude and altitude regions. Areas of high conservation significance need to be prioritised for management, to prevent further landscape‐scale change under current climate trajectories.
Lack of general associations between intertidal assemblages and rock hardness
Authors: Janetzki Nathan , Benkendorff Kirsten , Fairweather Peter G. 
Published: January 2021

AbstractDifferent assemblages of intertidal biota may be associated with the hardness of the rock type that comprises the seashore. However, very few published studies have investigated mobile and sessile assemblage differences between hardness classes. To remedy this, we investigated the physical attributes and biotic assemblages of 12 rock platforms across two bioregions, encompassing seven rock types categorised into either the soft (≤4 using Moh’s scale of scratch hardness) or hard (>4 on Moh’s scale) classes. Rock types from the soft versus hard classes differed physically, but the biotic assemblages showed few general differences between hardness classes. Instead, most biotic differences associated with rock hardness were specific to just one of the marine bioregions sampled, not both. Hardness‐related assemblage differences were only weakly‐to‐moderately correlated with hardness differences in mineralogy or microhabitat density. The detection of bioregion‐specific hardness differences for intertidal assemblages, rather than general hardness class trends, indicate that the type of rock comprising the seashore in each bioregion may be more strongly associated with the biotic patterns identified than hardness per se.
Elastase and exacerbation of neutrophil innate immunity are involved in multi‐visceral manifestations of COVID‐19
Authors: Guéant Jean‐Louis , Guéant‐Rodriguez Rosa‐Maria , Fromonot Julien , Oussalah Abderrahim , Louis Huguette , Chery Celine , Gette Mickael , Gleye Stanislas , Callet Jonas , Raso Jeremie , Blanchecotte François , Lacolley Patrick , Guieu Régis , Regnault Véronique 
Published: January 2021

AbstractBackgroundMany arguments suggest that neutrophils could play a prominent role in COVID‐19. However, the role of key components of neutrophil innate immunity in severe forms of COVID‐19 has deserved insufficient attention. We aimed to evaluate the involvement of neutrophil elastase, histone‐DNA, and DNases in systemic and multi‐organ manifestations of COVID‐19.MethodsWe performed a multicenter study of markers of neutrophil innate immunity in 155 cases consecutively recruited in a screening center, local hospitals, and two regional university hospitals. The cases were evaluated according to clinical and biological markers of severity and multi‐organ manifestations and compared to 35 healthy controls.ResultsBlood neutrophil elastase, histone‐DNA, myeloperoxidase‐DNA, and free dsDNA were dramatically increased, and DNase activity was decreased by 10‐fold, compared with controls. Neutrophil elastase and histone‐DNA were associated with intensive care admission, body temperature, lung damage, and markers of cardiovascular outcomes, renal failure, and increased interleukin‐6 (IL‐6), IL‐8, and CXCR2. Neutrophil elastase was an independent predictor of the computed tomography score of COVID‐19 lung damage and the number of affected organs, in multivariate analyses. The increased blood concentrations of NE and neutrophil extracellular traps were related to exacerbation of neutrophil stimulation through IL‐8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease in blood DNase activity.ConclusionOur results point out the key role of neutrophil innate immunity exacerbation in COVID‐19. Neutrophil elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID‐19.
Increased risk of dementia in hypothyroidism: A Danish nationwide register‐based study
Authors: Thvilum Marianne , Brandt Frans , Lillevang‐Johansen Mads , Folkestad Lars , Brix Thomas H. , Hegedüs Laszlo 
Published: January 2021

AbstractObjectiveGlobally, the prevalence of individuals with dementia is increasing, and identification of risk factors is of paramount interest. Using population‐based registers, we evaluated whether hypothyroidism is a risk factor for dementia.DesignRegister‐based cohort study.Patients and MethodsRisk of dementia was evaluated in two cohorts. The DNPR cohort comprises 111,565 hypothyroid patients, diagnosed between 1995 and 2012, and 446,260 euthyroid age‐ and sex‐matched individuals (median follow‐up 6.2 years). The OPENTHYRO cohort comprises 233,844 individuals with at least one measurement of serum thyrotropin (TSH) between 1995 and 2011, of whom 2,894 had hypothyroidism (median follow‐up 7.2 years). Primary outcome was dementia defined as an International Classification of Diseases 10 code, or prescription of medicine for dementia.ResultsIn the DNPR cohort, risk of dementia was significantly increased in subjects with hypothyroidism (HR 1.22; 95% CI: 1.17–1.27), which attenuated after adjusting for pre‐existing comorbidity (HR 0.82; 95% CI: 0.79‐0.86). Stratification of age into ≤56 and >56 years showed an inverse relationship between age and risk of dementia (HR≤56 years. 2.03; 95% CI: 1.62–2.53 and HR>56 years. 1.00; 95% CI: 0.96–1.05). In the OPENTHYRO cohort, the risk of dementia was significantly increased for each 6 months of elevated TSH (HR 1.12; 95% CI: 1.07–1.16).ConclusionsHypothyroidism is associated with increased risk of dementia. The association is influenced by comorbidity and age. Every 6 months of elevated TSH increased the risk of dementia by 12%, suggesting that also the length of hypothyroidism influences the risk of dementia.
Vocal development in a large‐scale crosslinguistic corpus
Authors: Cychosz Margaret , Cristia Alejandrina , Bergelson Elika , Casillas Marisa , Baudet Gladys , Warlaumont Anne S. , Scaff Camila , Yankowitz Lisa , Seidl Amanda 
Published: January 2021

AbstractThis study evaluates whether early vocalizations develop in similar ways in children across diverse cultural contexts. We analyze data from daylong audio recordings of 49 children (1–36 months) from five different language/cultural backgrounds. Citizen scientists annotated these recordings to determine if child vocalizations contained canonical transitions or not (e.g., “ba” vs. “ee”). Results revealed that the proportion of clips reported to contain canonical transitions increased with age. Furthermore, this proportion exceeded 0.15 by around 7 months, replicating and extending previous findings on canonical vocalization development but using data from the natural environments of a culturally and linguistically diverse sample. This work explores how crowdsourcing can be used to annotate corpora, helping establish developmental milestones relevant to multiple languages and cultures. Lower inter‐annotator reliability on the crowdsourcing platform, relative to more traditional in‐lab expert annotators, means that a larger number of unique annotators and/or annotations are required, and that crowdsourcing may not be a suitable method for more fine‐grained annotation decisions. Audio clips used for this project are compiled into a large‐scale infant vocalization corpus that is available for other researchers to use in future work.