bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-preferred contrast responses in the Drosophila motion pathways reveal a receptive field structure that explains a common visual illusion
Authors: Gruntman Eyal , Reimers Pablo , Romani Sandro , Reiser Michael B. 
Published: May 2021

SummaryDiverse sensory systems, from audition to thermosensation, feature a separation of inputs into ON (increments) and OFF (decrements) signals. In the Drosophila visual system, separate ON and OFF pathways compute the direction of motion, yet anatomical and functional studies have identified some crosstalk between these channels. We used this well-studied circuit to ask whether the motion computation depends on ON-OFF pathway crosstalk. Using whole-cell electrophysiology we recorded visual responses of T4 (ON) and T5 (OFF) cells and discovered that both cell types are also directionally selective in response to non-preferred contrast motion. We mapped T4s’ and T5s’ composite ON-OFF receptive fields and found they share a similar spatiotemporal structure. We fit a biophysical model to these receptive fields that accurately predicts directionally selective T4 and T5 responses to both ON and OFF moving stimuli. This model also provides a detailed mechanistic explanation for the directional-preference inversion in response to a prominent visual illusion, a result we corroborate with electrophysiological recordings and behavioral responses of flying flies.
Genomic consequences of domestication of the Siamese fighting fish
Authors: Kwon Young Mi , Vranken Nathan , Hoge Carla , Lichak Madison R , Francis Kerel X , Camacho-Garcia Julia , Bista Iliana , Wood Jonathan , McCarthy Shane , Chow William , Tan Heok Hui , Howe Kerstin , Bandara Sepalika , von Lintig Johannes , Rüber Lukas , Durbin Richard , Svardal Hannes , Bendesky Andres 
Published: May 2021

AbstractSiamese fighting fish, commonly known as betta, are among the world’s most popular and morphologically diverse pet fish, but the genetic processes leading to their domestication and phenotypic diversification are largely unknown. We assembled de novo the genome of a wildBetta splendensand whole-genome sequenced multiple individuals across five species within theB. splendensspecies complex, including wild populations and domesticated ornamental betta. Given our estimate of the mutation rate from pedigrees, our analyses suggest that betta were domesticated at least 1,000 years ago, centuries earlier than previously thought. Ornamental betta individuals have variable contributions from otherBettaspecies and have also introgressed into wild populations of those species. We identifydmrt1as the main sex determination gene in ornamental betta but not in wildB. splendens, and find evidence for recent directional selection at the X-allele of the locus. Furthermore, we find genes with signatures of recent, strong selection that have large effects on color in specific parts of the body, or the shape of individual fins, and are almost all unlinked. Our results demonstrate how simple genetic architectures paired with anatomical modularity can lead to vast phenotypic diversity generated during animal domestication, and set the stage for using betta as a modern system for evolutionary genetics.One-Sentence SummaryGenomic analyses reveal betta fish were domesticated more than 1,000 years ago and the genes that changed in the process.
ACE2 glycans preferentially interact with the RBD of SARS-CoV-2 over SARS-CoV
Authors: Acharya Atanu , Lynch Diane L. , Pavlova Anna , Pang Yui Tik , Gumbart James C. 
Published: May 2021

ABSTRACTWe report a distinct difference in the interactions of the glycans of the host-cell receptor, ACE2, with SARS-CoV-2 and SARS-CoV S-protein receptor-binding domains (RBDs). Our analysis demonstrates that the ACE2 glycan at N90 may offer protection against infections of both coronaviruses, while the ACE2 glycan at N322 enhances interactions with the SARS-CoV-2 RBD. The interactions of the ACE2 glycan at N322 with SARS-CoV RBD are blocked by the presence of the RBD glycan at N357 of the SARS-CoV RBD. The absence of this glycosylation site on SARS-CoV-2 RBD may enhance its binding with ACE2.
Characterizing stored red blood cells using ultra-high throughput holographic cytometry
Authors: Park Han Sang , Price Hillel , Ceballos Silvia , Chi Jen-Tsan , Wax Adam 
Published: May 2021

AbstractHolographic cytometry is introduced as an ultra-high throughput implementation of quantitative phase image based on off-axis interferometry of cells flowing through parallel microfluidic channels. Here, it is applied for characterizing morphological changes of red blood cells during storage under regular blood bank condition. The approach allows high quality phase imaging of a large number of cells greatly extending our ability to study cellular phenotypes using individual cell images. Holographic cytology measurements show multiple physical traits of the cells, including optical volume and area, which are observed to consistently change over the storage time. In addition, the large volume of cell imaging data can serve as training data for machine learning algorithms. For the study here, logistic regression is used to classify the cells according to the storage time points. The results of the classifiers demonstrate the potential of holographic cytometry as a diagnostic tool.
Environmental filtering in marine fish communities is weakened during severe hypoxia season
Authors: Shinohara Naoto , Hongo Yuki , Ichinokawa Momoko , Nishijima Shota , Sawayama Shuhei , Kurogi Hiroaki , Uto Yasuyuki , Mita Hisanori , Ishii Mitsuhiro , Kusano Akane , Akimoto Seiji 
Published: May 2021

AbstractCompositional variation among local communities reflects the differences in abiotic environments, though the extent of the influence varies in natural systems. Generally, the environmental filtering is expected to be strong if the environmental gradient encompasses severe habitats where species sorting is highly likely to work. However, this hypothesis has rarely been tested in dynamic systems, where the higher dispersal ability of species allows them to easily respond to stressful environments. Here, with the dynamics of fish communities in a Japanese bay revealed by environmental DNA analyses as a model case, we examined how harmful seasonal hypoxia (low concentration of oxygen in bottom waters in summer) affected the strength of environmental filtering. We found that, in summer, dissolved oxygen (DO) concentration was significantly low and fish species richness decreased in the bottom water compared to the surface, suggesting that the organisms were adversely affected by the hypoxia. At the same time, the between-depths heterogeneity in DO concentration was larger, but species composition was less divergent and the influence of DO on species composition appeared weaker during summer. These results imply that environmental filtering is weakened when the bottom water was characterized by extremely severe environments. Furthermore, there was a shift in the species occurrence from bottom to surface waters in summer that was consistent across species, suggesting that the extremely severe hypoxia adversely affected fish species irrespective of their identity. These results collectively suggest that environmental filtering is weaker during summer despite more severity and heterogeneity in environments, most likely because individual movements to avoid unpreferable environments in the bottom waters occurred quasi-neutrally. By providing evidence against the prevailing understanding that environmental filtering strongly works in severe environments, these findings invoke further investigation on how the filtering acts in various conditions.
Sequence-based correction of barcode bias in massively parallel reporter assays
Authors: Lee Dongwon , Kapoor Ashish , Lee Changhee , Mudgett Michael , Beer Michael A. , Chakravarti Aravinda 
Published: May 2021

ABSTRACTMassively parallel reporter assays (MPRA) are a high-throughput method for evaluatingin vitroactivities of thousands of candidate cis-regulatory elements (CREs). In these assays, candidate sequences are cloned upstream or downstream of a reporter gene tagged by unique DNA sequences. However, tag sequences may themselves affect reporter gene expression and lead to major potential biases in the measured cis-regulatory activity. Here, we present a sequence-based method for correcting tag sequence-specific effects and demonstrate that our method can significantly reduce this source of variation, and improve the identification of functional regulatory variants by MPRAs. We also show that our model captures sequence features associated with post-transcriptional regulation of mRNA. Thus, this new method helps to not only improve detection of regulatory signals in MPRA experiments but also to design better MPRA protocols.
Missingness Adapted Group Informed Clustered (MAGIC)-LASSO: A novel paradigm for prediction in data with widespread non-random missingness
Authors: Gentry Amanda Elswick , Kirkpatrick Robert M. , Peterson Roseann E. , Webb B. Todd 
Published: May 2021

AbstractThe availability of large-scale biobanks linking rich phenotypes and biological measures is a powerful opportunity for scientific discovery. However, real-world collections frequently have extensive non-random missingness. While missing data prediction is possible, performance is significantly impaired by block-wise missingness inherent to many biobanks. To address this, we developed Missingness Adapted Group-wise Informed Clustered (MAGIC)-LASSO which performs hierarchical clustering of variables based on missingness followed by sequential Group LASSO within clusters. Variables are pre-filtered for missingness and balance between training and target sets with final models built using stepwise inclusion of features ranked by completeness. This research has been conducted using the UK Biobank (n>500k) to predict unmeasured Alcohol Use Disorders Identification Test (AUDIT) scores. The phenotypic correlation between measured and predicted total score was 0.67 while genetic correlations between independent subjects was high >0.86, demonstrating the method has significant accuracy and utility.
Decitabine Reactivation of FoxM1-Dependent Endothelial Regeneration and Vascular Repair for Potential Treatment of Elderly ARDS and COVID-19 Patients
Authors: Huang Xiaojia , Zhang Xianming , Machireddy Narsa , Mutlu Gökhan M. , Fang Yun , Wu David , Zhao You-Yang 
Published: May 2021

AbstractAging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS) and COVID-19. We repot that aging impairs the intrinsic FoxM1-dependent endothelial regeneration and vascular repair program and causes persistent lung injury and high mortality following sepsis. Therapeutic gene transduction ofFOXM1in vascular endothelium or treatment with FDA-approved drug Decitabine was sufficient to reactivate FoxM1-dependent lung endothelial regeneration in aged mice, reverse aging-impaired resolution of inflammatory injury, and promote survival. In COVID-19 lung autopsy samples, FOXM1 expression was not induced in vascular endothelial cells of elderly patients in contrast to mid-age patients. Thus, Decitabine reactivation of FoxM1-dependent vascular repair represents a potential effective therapy for elderly COVID-19 and non-COVID-19 ARDS patients.
Comparing Expression of OAS-RNaseL Pathway-Related Genes in SARS-CoV-2 and Similar Viruses
Authors: Chakravarty Nikhil , Edillor Penelope A. , Huang Andy P. , Torres Giovanni A. , Usmani Manal T. , Kadandale Pavan 
Published: May 2021

AbstractThe COVID-19 pandemic, caused by the virus SARS-CoV-2, has been a major public health emergency and has caused millions of deaths worldwide to date. Due to the novel nature of the virus, efforts across the world are underway to better understand the molecular pathogenesis of SARS-CoV-2 and how it interacts with host immune responses. One important branch of the innate immune response, the interferon system, triggers the expression of many effector mechanisms known to be powerful antagonists against many pathogenic viruses. One such interferon stimulated mechanism is the OAS-RNaseL pathway, which is known to trigger the degradation of viral RNA in infected host cells. Our study seeks to utilize publicly available transcriptomic data to analyze the host cell OAS-RNaseL pathway to SARS-CoV-2 infection. We hoped to gain an understanding of the importance of the pathway in controlling SARS-CoV-2 infection and whether or not the pathway could be exploited therapeutically. Our findings demonstrated that upregulation of OAS-RNaseL pathway genes in response to SARS-CoV-2 infection varies based on cell type and appeared to correlate with ACE2 receptor expression. Pathway responses to other viruses like SARS-CoV and MERS-CoV were found to parallel those to SARS-CoV-2, suggesting common response patterns by the pathway to these viruses. Overall, these results demonstrate that the OAS-RNaseL pathway could contribute to control of SARS-CoV-2 infection. Further studies on various mechanistic actions by the pathway would need to be conducted to fully understand its role in host defense and therapy.
3C-seq-captured chromosome conformation of the hyperthermophilic archaeon Thermofilum adornatum
Authors: Sobolev Andrey , Solovyev Mikhail , Ivanova Valeria , Kochetkova Tatiana , Merkel Alexandr , Razin Sergey , Ulianov Sergey , Tyakht Alexander 
Published: May 2021

AbstractThree-dimensional structure of chromosomes displays diverse patterns across the tree of life, with compartments, interaction domains and loops being quite universally observed. The archaeal kingdom remains understudied to this extent so far, despite representing an interesting area from evolutionary and other perspectives.Here we describe the spatial chromosomal organization of a hyperthermophilic crenarchaeon Thermofilum adornatum strain 1910b based on high-throughput chromosome conformation capture (3C-seq) approach. The chromosome contact map showed a curved secondary diagonal almost orthogonal to the main one. No evidence of chromosome loops was present. We were able to identify boundaries of different strengths between chromosome interaction domains (CIDs) albeit moderate. The plaid-like patterns previously reported for Sulfolobus archaea were not observed. However, the calculation of A/B compartments divided the genome into 2 domains that were different by the density of predicted highly expressed genes and location of origins.Further comparison of these domains with whole-genome gene expression profiles will allow to test whether these domains represent expression-associated compartments. If so, it is possible that they represent primitive compartments evolutionarily older than the plaid patterns of Sulfolobus and higher eukaryotes. Further exploration of 3D chromatin in all branches of archaeal diversity will elucidate the evolution of the links between structural and functional organization in live organisms.
Limited within-host diversity and tight transmission bottlenecks limit SARS-CoV-2 evolution in acutely infected individuals
Authors: Braun Katarina , Moreno Gage , Wagner Cassia , Accola Molly A. , Rehrauer William M. , Baker David , Koelle Katia , O’Connor David H. , Bedford Trevor , Friedrich Thomas C. , Moncla Louise H. 
Published: May 2021

AbstractThe recent emergence of divergent SARS-CoV-2 lineages has raised concerns about the role of selection within individual hosts in propagating novel variants. Of particular concern are variants associated with immune escape and/or enhanced transmissibility. Though growing evidence suggests that novel variants can arise during prolonged infections, most infections are acute. Understanding the extent to which variants emerge and transmit among acutely infected hosts is therefore critical for predicting the pace at which variants resistant to vaccines or conferring increased transmissibility might emerge in the majority of SARS-CoV-2 infections. To characterize how within-host diversity is generated and propagated, we combine extensive laboratory and bioinformatic controls with metrics of within- and between-host diversity to 133 SARS-CoV-2 genomes from acutely infected individuals. We find that within-host diversity during acute infection is low and transmission bottlenecks are narrow, with very few viruses founding most infections. Within-host variants are rarely transmitted, even among individuals within the same household. Accordingly, we also find that within-host variants are rarely detected along phylogenetically linked infections in the broader community. Together, these findings suggest that efficient selection and transmission of novel SARS-CoV-2 variants is unlikely during typical, acute infection.One Sentence SummaryPatterns of SARS-CoV-2 within hosts suggest efficient selection and transmission of novel variants is unlikely during typical, acute infection.
RelA-SpoT Homologue toxins pyrophosphorylate the CCA end of tRNA to inhibit protein synthesis
Authors: Kurata Tatsuaki , Brodiazhenko Tetiana , Oliveira Sofia Raquel Alves , Roghanian Mohammad , Turnbull Kathryn Jane , Bulvas Ondřej , Takada Hiraku , Taman Hedvig , Ainelo Andres , Pohl Radek , Rejman Dominik , Tenson Tanel , Garcia-Pino Abel , Atkinson Gemma C. , Hauryliuk Vasili 
Published: May 2021

SummaryRelA-SpoT Homolog (RSH) enzymes control bacterial physiology through synthesis and degradation of the nucleotide alarmone (p)ppGpp. We recently discovered multiple families of Small Alarmone Synthetase (SAS) RSH acting as toxins of toxin-antitoxin (TA) modules, with the FaRel subfamily of toxSAS abrogating bacterial growth by producing an analogue of (p)ppGpp, (pp)pApp. Here we probe the mechanism of growth arrest employed by four experimentally unexplored subfamilies of toxSAS: FaRel2, PhRel, PhRel2 and CapRel. Surprisingly, all these toxins specifically inhibit protein synthesis. To do so, they transfer a pyrophosphate moiety from ATP to the tRNA 3′ CCA. The modification inhibits both tRNA aminoacylation and the sensing of cellular amino acid starvation by the ribosome-associated RSH RelA. Conversely, we show that some Small Alarmone Hydrolase (SAH) RSH enzymes can reverse the pyrophosphorylation of tRNA to counter the growth inhibition by toxSAS. Collectively, we establish RSHs as a novel class of RNA-modifying enzymes.
Covariance-based information processing in reservoir computing systems
Authors: Lawrie Sofía , Moreno-Bote Rubén , Gilson Matthieu 
Published: May 2021

AbstractIn biological neuronal networks, information representation and processing are achieved through plasticity learning rules that have been empirically characterized as sensitive to second and higher-order statistics in spike trains. However, most models in both computational neuroscience and machine learning aim to convert diverse statistical properties in inputs into first-order statistics in outputs, like in modern deep learning networks. In the context of classification, such schemes have merit for inputs like static images, but they are not well suited to capture the temporal structure in time series. In contrast, the recently developed covariance perceptron uses second-order statistics by mapping input covariances to output covariances in a consistent fashion. Here, we explore the applicability of covariance-based perceptron readouts in reservoir computing networks to classify synthetic multivariate time series structured at different statistical orders (first and second). We show that the second-order framework outperforms or matches the classical mean paradigm in terms of accuracy. Our results highlight a nontrivial relationship between input and reservoir properties in generating the output reservoir activity, which suggests an important role for recurrent connectivity in transforming information representations in biologically inspired architectures. Finally, we solve a speech recognition task for the classification of spoken digits to further demonstrate the potential of covariance-based decoding for real data.
Low-cost, handheld near-infrared spectroscopy for root dry matter content prediction in cassava
Authors: Hershberger Jenna , Mbanjo Edwige Gaby Nkouaya , Peteti Prasad , Ikpan Andrew Smith , Ogunpaimo Kayode , Nafiu Kehinde , Rabbi Ismail Y. , Gore Michael A. 
Published: May 2021

ABSTRACTOver 800 million people across the tropics rely on cassava as a major source of calories. While the root dry matter content (RDMC) of this starchy root crop is important for both producers and consumers, characterization of RDMC by traditional methods is time-consuming and laborious for breeding programs. Alternate phenotyping methods have been proposed but lack the accuracy, cost, or speed ultimately needed for cassava breeding programs. For this reason, we investigated the use of a low-cost, handheld NIR spectrometer for field-based RDMC prediction in cassava. Oven-dried measurements of RDMC were paired with 21,044 scans of roots of 376 diverse clones from 10 field trials in Nigeria and grouped into training and test sets based on cross-validation schemes relevant to plant breeding programs. Mean partial least squares regression model performance ranged from R2p= 0.62 - 0.89 for within-trial predictions, which is within the range achieved with laboratory-grade spectrometers in previous studies. Relative to other factors, model performance was highly impacted by the inclusion of samples from the same environment in both the training and test sets. Random forest variable importance analysis of root spectra revealed increased importance in a region previously identified as predictive of water content in plants (~950 - 990 nm). With appropriate model calibration, the tested spectrometer will allow for field-based collection of spectral data with a smartphone for accurate RDMC prediction and potentially other quality traits, a step that could be easily integrated into existing harvesting workflows of cassava breeding programs.CORE IDEASA low-cost, handheld near-infrared spectrometer was tested for phenotyping of cassava rootsPlant breeding-relevant cross-validation schemes were used for predictionsHigh prediction accuracies were achieved for cassava root dry matter contentA spectral region predictive of plant water content was identified as important