bluuebunny/crossref_metadata_2025_split huggingface dataset:
A naturalistic environment to study natural social behaviors and cognitive tasks in freely moving monkeys
Authors: Jacob Georgin , Katti Harish , Cherian Thomas , Das Jhilik , KA Zhivago , Arun SP 
Published: September 2020

ABSTRACTMacaque monkeys are widely used to study the neural basis of cognition. In the traditional approach, the monkey is brought into a lab to perform tasks while it is restrained to obtain stable gaze tracking and neural recordings. This unnatural setting prevents studying brain activity during natural, social and complex behaviors. Here, we designed a naturalistic environment with an integrated behavioral workstation that enables complex task training with viable gaze tracking in freely moving monkeys. We used this facility to train monkeys on a challenging same-different task. Remarkably, this facility enabled a naïve monkey to learn the task merely by observing trained monkeys. This social training was faster primarily because the naïve monkey first learned the task structure and then the same-different rule. We propose that such hybrid environments can be used to study brain activity during natural behaviors as well as during controlled cognitive tasks.
Electronic cigarette vaping triggers lipid mediated vocal fold mucosal injury
Authors: Lungova Vlasta , Thibeault Susan L. 
Published: September 2020

AbstractElectronic cigarettes (e-cigs) are nicotine delivery systems that have been touted as safer alternatives to smoking. A recently reported case of epiglottitis revealed a connection between vaping and swollen laryngeal and vocal fold (VF) structures that can lead to acute life-threatening airway obstruction. The clinical course and biopsy revealed direct epithelial injury and subsequent inflammatory reaction. Here we show that we were able to recapitulate this phenomenon in in vitro conditions. Exposure of engineered VF mucosae to 5% e-cig vapor extract for one week induced cellular damage in VF luminal epithelial cells, disrupting mucosal homeostasis and mucosal innate immune responses. Epithelial erosion was likely caused by the accumulation of solvents and lipid particles, most likely medium chain fatty acids, in the cytosol and intercellular spaces, which altered lipid metabolism and plasma membrane properties. In summary, vaping represents a threat to the VF mucosa health and airway protection.
Neurons learn by predicting future activity
Authors: Luczak Artur , McNaughton Bruce L. , Kubo Yoshimasa 
Published: September 2020

AbstractUnderstanding how the brain learns may lead to machines with human-like intellectual capacities. However, learning mechanisms in the brain are still not well understood. Here we demonstrate that the ability of a neuron to predict its future activity may provide an effective mechanism for learning in the brain. We show that comparing a neuron’s predicted activity with the actual activity provides a useful learning signal for modifying synaptic weights. Interestingly, this predictive learning rule can be derived from a metabolic principle, where neurons need to minimize their own synaptic activity (cost), while maximizing their impact on local blood supply by recruiting other neurons. This reveals an unexpected connection that learning in neural networks could result from simply maximizing the energy balance by each neuron. We show how this mathematically derived learning rule can provide a theoretical connection between diverse types of brain-inspired algorithms, such as: Hebb’s rule, BCM theory, temporal difference learning and predictive coding. Thus, this may offer a step toward development of a general theory of neuronal learning. We validated this predictive learning rule in neural network simulations and in data recorded from awake animals. We found that in the sensory cortex it is indeed possible to predict a neuron’s activity ∼10-20ms into the future. Moreover, in response to stimuli, cortical neurons changed their firing rate to minimize surprise: i.e. the difference between actual and expected activity, as predicted by our model. Our results also suggest that spontaneous brain activity provides “training data” for neurons to learn to predict cortical dynamics. Thus, this work demonstrates that the ability of a neuron to predict its future inputs could be an important missing element to understand computation in the brain.
An optimal set of inhibitors for Reverse Engineering via Kinase Regularization
Authors: Rata Scott , Gruver Jonathan Scott , Trikoz Natalia , Lukyanov Alexander , Vultaggio Janelle , Ceribelli Michele , Thomas Craig , Gujral Taran Singh , Kirschner Marc W. , Peshkin Leonid 
Published: September 2020

AbstractWe present a comprehensive resource of 257 kinase inhibitor profiles against 365 human protein kinases using gold-standard kinase activity assays. We show the utility of this dataset with an improved version of Kinome Regularization (KiR) to deconvolve protein kinases involved in a cellular phenotype. We assayed protein kinase inhibitors against more than 70% of the human protein kinome and chose an optimal subset of 58 inhibitors to assay at ten doses across four orders of magnitude. We demonstrate the effectiveness of KiR to identify key kinases by using a quantitative cell migration assay and updated machine learning methods. This approach can be widely applied to biological problems for which a quantitative phenotype can be measured and which can be perturbed with our set of kinase inhibitors.
Road to ruin? Urbanization increases herbivory in a tropical wildflower but does not lead to the evolution of chemical defence traits
Authors: Rivkin L. Ruth , Moura Antonio 
Published: September 2020

AbstractUrbanization is associated with numerous changes to the biotic and abiotic environment, many of which degrade the environment and lead to a loss of biodiversity. Cities often have elevated pollution levels that harm wildlife; however, the increased concentration of some pollutants can fertilize urban plants, leading to corresponding positive effects on herbivore populations. Increases in herbivory rates may lead to natural selection for greater defence phenotypes in plants. However, evidence supporting increased herbivory leading to the evolution of plant defence in urban environments is contradictory, and entirely absent from tropical regions of the world. To address these research gaps, we evaluated herbivory onTurnera subulata, a common urban wildflower, along an urbanization gradient in Joao Pessoa, Brazil. We predicted that higher rates of herbivory in urban areas would lead these populations to evolve cyanogenesis, a chemical defence found in a closely relatedTurneraspecies. We assessed herbivory and screened for cyanogenesis in 32 populations along the urbanization gradient, quantified by the Human Footprint Index. Our results show that urbanization is significantly associated with increased herbivory rates inT. subulatapopulations. Despite elevated herbivory, we found no evidence for the evolution of cyanongenesis in any of the populations, suggesting that the fitness effects of leaf herbivory are not extreme enough to select for the evolution of plant defence in these populations. Habitat loss, predator release, and nutrient enrichment likely act together to increase the abundance of herbivorous arthropods, influencing the herbivory patterns observed in our study.
Brief Report: High-Quality Masks Can Reduce Infections and Deaths in the US
Authors: Rosenstrom Erik , Oruc Buse Eylul , Ivy Julie , Keskinocak Pinar , Mayorga Maria E. , Swann Julie L. 
Published: September 2020

ABSTRACTObjectivesTo evaluate the effectiveness of widespread adoption of masks or face coverings to reduce community transmission of the SARS-CoV-2 virus that causes Covid-19.MethodsWe employed an agent-based stochastic network simulation model, where Covid-19 progresses across census tracts according to a variant of SEIR. We considered a mask order that was initiated 3.5 months after the first confirmed Covid-19 case. We evaluated scenarios where wearing a mask reduces transmission and susceptibility by 50% or 80%; an individual wears a mask with a probability of 0%, 20%, 40%, 60%, 80%, or 100%.ResultsIf 60% of the population wears masks that are 50% effective, this decreases the cumulative infection attack rate (CAR) by 25%, the peak prevalence by 51%, and the population mortality by 25%. If 100% of people wear masks (or 60% wear masks that are 80% effective), this decreases the CAR by 38%, the peak prevalence by 67%, and the population mortality by 40%.ConclusionsAfter community transmission is present, masks can significantly reduce infections.
SARS-CoV-2 cell entry gene ACE2 expression in immune cells that infiltrate the placenta in infection-associated preterm birth
Authors: Lye Phetcharawan , Dunk Caroline E. , Zhang Jianhong , Wei Yanxing , Nakpu Jittanan , Hamada Hirotaka , Imperio Guinever E , Bloise Enrrico , Matthews Stephen G , Lye Stephen J 
Published: September 2020

AbstractCOVID-19 infection during pregnancy is associated with an increased incidence of preterm birth but neonatal infection is rare. We assessed pathways by which SARS-CoV-2 could access the placenta and contribute to fetal transmission. Placentas from pregnancies complicated with chorioamnionitis (ChA), exhibited increased expression of ACE2 mRNA. Treatment of 2nd trimester placental explants with LPS, induced an acute increase in cytokine expression followed by ACE2 mRNA. Placental ACE2 protein localized to syncytiotrophoblast, in fetal blood vessels and M1/M2 macrophage and neutrophils within the villous stroma. Increased numbers of M1 macrophage and neutrophils were present in the placenta of ChA pregnancies. Maternal peripheral immune cells (mainly granulocytes and monocytes) express the ACE2 mRNA and protein. These data suggest that in COVID19 positive pregnancies complicated by ChA, ACE2 positive immune cells have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.
The functional and phenotypic diversity of single T-cell infiltrates in human colorectal cancer as correlated with clinical outcome
Authors: Masuda Kazuya , Kornberg Adam , Lin Sijie , Ho Patricia , Secener Kerim , Suek Nathan , Bacarella Alyssa M. , Ingham Matthew , Rosario Vilma , Al-Masrou Ahmed M. , Lee-Kong Steven A. , Kiran P. Ravi , Yan Kelley S. , Stoeckius Marlon , Smibert Peter , Oberstein Paul E. , Sims Peter A. , Han Arnold 
Published: September 2020

AbstractAlthough degree of T-cell infiltration in CRC was shown to correlate with a positive prognosis, the contribution of phenotypically and functionally distinct T cell subtypes within tumors remains unclear. We analyzed 37,931 single T cells with respect to transcriptome, TCR sequence and 23 cell surface proteins, from tumors and adjacent normal colon of 16 patients. Our comprehensive analysis revealed two phenotypically distinct cytotoxic T cell populations within tumors, including positively prognostic effector memory cells and non-prognostic resident memory cells. These cytotoxic T cell infiltrates transitioned from effector memory to resident memory in a stage-dependent manner. We further defined several Treg subpopulations within tumors. While Tregs overall were associated with positive clinical outcomes, CD38+peripherally-derived Tregs, phenotypically related to Th17 cells, correlated with poor outcomes independent of cancer stage. Thus, our data highlight the diversity of T cells in CRC and demonstrate the prognostic significance of distinct T cell subtypes, which could inform therapeutic strategies.
Evidence for associations between Rey-Osterrieth Complex Figure test and motor skill learning in older adults
Authors: VanGilder Jennapher Lingo , Lohse Keith R. , Duff Kevin , Wang Peiyuan , Schaefer Sydney Y. 
Published: September 2020

AbstractAge-related declines in motor learning may be related to poor visuospatial function. Thus, visuospatial testing could evaluate older adults’ potential for motor learning, which has implications for geriatric motor rehabilitation. To this end, the purpose of this study was to identify which visuospatial test is most predictive of motor learning within older adults. Forty-five nondemented older adults completed six standardized visuospatial tests, followed by three weekly practice sessions on a functional upper-extremity motor task. Participants were re-tested one month later on the trained task and another untrained upper-extremity motor task to evaluate the durability and generalizability of motor learning, respectively. Principal component analysis first reduced the dimensions of the visuospatial battery to two principal components for inclusion in a mixed-effects model that assessed one-month follow-up performance as a function of baseline performance and the principal components. Of the two components, only one was related to one-month follow-up. Factor loadings and post hoc analyses suggested that of the six visuospatial tests, the Rey-Osterrieth test (visual construction and memory) was related to one-month follow-up of the trained and untrained tasks. Thus, it may be plausible that older adults’ long-term motor learning capacity could be evaluated using the Rey-Osterrieth test, which would be feasible to administer prior to motor rehabilitation to indicate risk of non-responsiveness to therapy.
Understanding land-use response of bird communities in an arid ecosystem of India
Authors: Varun K , Dutta Sutirtha 
Published: September 2020

AbstractThe Indian Thar desert has lost much of its grasslands over the last few decades, mainly due to land-use change from pastoralism to agriculture. Expanding croplands and intensifying grazing pressures are popularly hypothesized to be major drivers of biodiversity loss in the region. Our study aims to investigate the effects of contemporary land-use change on bird communities of the Western Thar Desert.We surveyed 58 randomly laid line transects in a c2000 sq.km study area, to quantify parameters of bird community structure in three predominant land-use types viz. protected grasslands, rangelands, and non-irrigated croplands. Fieldwork for the study was conducted in the dry season (winter and summer) between December 2018 and April 2019.During winter, overall bird richness and abundance were highest in protected grasslands followed by non-irrigated croplands and rangelands. Protected grasslands also had a higher abundance of diet and habitat specialists. Compared to protected grasslands, density was lower in non-irrigated croplands and rangelands for 35% and 10% of species, respectively. A majority of the negatively affected species were insectivorous grassland specialists.Contrary to the pattern in winter, overall bird richness, abundance, community composition, and guild structure in summer were similar across three land-use types. Only one of the 17 analysed species had lower density in modified land-use types.Overall, protected grassland was the best habitat for birds and was specifically important for specialists, particularly during the winter. Rangelands and fallow croplands sustained most generalists at comparable densities but had severe negative impacts on specialists.Synthesis and application: Our results point out that low-intensity agro-pastoral land-uses can supplement, but not replace, protected areas in conservation of Thar desert’s avifaunal diversity. Our results are consistent with the idea of managing dryland habitats as agro-grassland mosaics with embedded protected areas, in order to reconcile human needs and biodiversity conservation at a landscape scale.
Glutamic acid promotes hair growth in mice
Authors: Jara Carlos Poblete , de Andrade Berti Beatriz , Mendes Natalia Ferreira , Engel Daiane F. , Zanesco Ariane Maria , Souza Gabriela Freitas , Velloso Lício Augusto , de Araujo Eliana Pereira 
Published: September 2020

AbstractGlutamic Acid is the main excitatory neurotransmitter in neurons. Abnormal distributions of the glutamic acid receptors have been shown in hyper proliferative models such as psoriasis and skin regeneration. However, the biological function of glutamic acid in the skin remains unclear. Usingex vivo, in vivoandin silicoapproaches, we showed for the first time that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased expression of genes related to apoptosis signaling in the skin. Also, we showed Glutamic acid increased viability and proliferation in cultured human keratinocyte. For the first time, we identified the excitotoxic GA concentration and we provided evidence for the existence of a novel skin signaling pathway mediated by a neurotransmitter controlling keratinocyte and hair follicle proliferation. In perspective, we anticipate our results could be the starting point to elucidate how exogenous glutamic acid from food intake or even endogenous GA from neuropsychiatric disorders modulate skin diseases.
A Tethered Ligand Assay to Probe the SARS-CoV-2 ACE2 Interaction under Constant Force
Authors: Bauer Magnus S. , Gruber Sophia , Milles Lukas F. , Nicolaus Thomas , Schendel Leonard C. , Gaub Hermann E. , Lipfert Jan 
Published: September 2020

ABSTRACTThe current COVID-19 pandemic has a devastating global impact and is caused by the SARS-CoV-2 virus. SARS-CoV-2 attaches to human host cells through interaction of its receptor binding domain (RBD) located on the viral Spike (S) glycoprotein with angiotensin converting enzyme-2 (ACE2) on the surface of host cells. RBD binding to ACE2 is a critical first step in SARS-CoV-2 infection. Viral attachment occurs in dynamic environments where forces act on the binding partners and multivalent interactions play central roles, creating an urgent need for assays that can quantitate SARS-CoV-2 interactions with ACE2 under mechanical load and in defined geometries. Here, we introduce a tethered ligand assay that comprises the RBD and the ACE2 ectodomain joined by a flexible peptide linker. Using specific molecular handles, we tether the fusion proteins between a functionalized flow cell surface and magnetic beads in magnetic tweezers. We observe repeated interactions of RBD and ACE2 under constant loads and can fully quantify the force dependence and kinetics of the binding interaction. Our results suggest that the SARS-CoV-2 ACE2 interaction has higher mechanical stability, a larger free energy of binding, and a lower off-rate than that of SARS-CoV-1, the causative agents of the 2002-2004 SARS outbreak. In the absence of force, the SARS-CoV-2 RBD rapidly (within ≤1 ms) engages the ACE2 receptor if held in close proximity and remains bound to ACE2 for 400-800 s, much longer than what has been reported for other viruses engaging their cellular receptors. We anticipate that our assay will be a powerful tool investigate the roles of mutations in the RBD that might alter the infectivity of the virus and to test the modes of action of neutralizing antibodies and other agents designed to block RBD binding to ACE2 that are currently developed as potential COVID-19 therapeutics.
TALE: Transformer-based protein function Annotation with joint sequence–Label Embedding
Authors: Cao Yue , Shen Yang 
Published: September 2020

AbstractMotivationFacing the increasing gap between high-throughput sequence data and limited functional insights, computational protein function annotation provides a high-throughput alternative to experimental approaches. However, current methods can have limited applicability while relying on data besides sequences, or lack generalizability to novel sequences, species and functions.ResultsTo overcome aforementioned barriers in applicability and generalizability, we propose a novel deep learning model, named Transformer-based protein function Annotation through joint sequence–Label Embedding (TALE). For generalizbility to novel sequences we use self attention-based transformers to capture global patterns in sequences. For generalizability to unseen or rarely seen functions, we also embed protein function labels (hierarchical GO terms on directed graphs) together with inputs/features (sequences) in a joint latent space. Combining TALE and a sequence similarity-based method, TALE+ outperformed competing methods when only sequence input is available. It even outperformed a state-of-the-art method using network information besides sequence, in two of the three gene ontologies. Furthermore, TALE and TALE+ showed superior generalizability to proteins of low homology and never/rarely annotated novel species or functions compared to training data, revealing deep insights into the protein sequence–function relationship. Ablation studies elucidated contributions of algorithmic components toward the accuracy and the generalizability.AvailabilityThe data, source codes and models are available athttps://github.com/Shen-Lab/TALEContactyshen@tamu.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Structural characterization of an RNA bound antiterminator protein reveal a successive binding mode
Authors: Walshe James L. , Patel Karishma , Ataide Sandro F. 
Published: September 2020

ABSTRACTIn bacteria, rho-independent termination occurs through the formation of an intrinsic RNA terminator loop, which disrupts the RNA polymerase elongation complex, resulting in dissociation from the DNA template. ANTAR domains are a class of antiterminator that bind and stabilise mutually exclusive dual hexaloop motifs within the nascent RNA chain to prevent terminator loop formation. We have determined the structures of the dimeric ANTAR domain protein EutV, fromE. faecialis,both in the absence of and in complex with the dual hexaloop RNA target. The structures illustrate the conformational changes that occur upon RNA binding and reveal the molecular interactions between the ANTAR domains and RNA are restricted to a single hexaloop of the motif. Our findings thereby redefine the minimal ANTAR domain binding motif to a single hexaloop and revise the current model for ANTAR-mediated antitermination. These insights will inform and facilitate the discovery of novel ANTAR domain RNA targets.
MonaGO: a novel Gene Ontology enrichment analysis visualisation system
Authors: Xin Ziyin , Cai Yujun , Dang Louis T. , Burke Hannah M.S. , Revote Jerico , Nim Hieu T. , Li Yuan-Fang , Ramialison Mirana 
Published: September 2020

AbstractMonaGO is a novel web-based visualisation system that provides an intuitive, interactive and responsive interface for performing gene ontology (GO) enrichment analysis and visualising the results. MonaGO combines dynamic clustering and interactive visualisation as well as customisation options to assist biologists in obtaining meaningful representation of overrepresented GO terms, producing simplified outputs in an unbiased manner. MonaGO supports gene lists as well as GO terms as inputs. Visualisation results can be exported as high-resolution images or restored in new sessions, allowing reproducibility of the analysis. An extensive comparison between MonaGO and 11 state-of-the-art GO enrichment visualisation tools based on 9 features revealed that MonaGO is the only platform that simultaneously allows interactive visualisation within one single output page, directly accessible through a web browser with customisable display options. In summary, MonaGO will facilitate the interpretation of GO analysis and will assist the biologists into the representation of the results.