bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating muscle activation from EMG using deep learning-based dynamical systems models
Authors: Wimalasena Lahiru N. , Braun Jonas F. , Keshtkaran Mohammad Reza , Hofmann David , Gallego Juan Álvaro , Alessandro Cristiano , Tresch Matthew C. , Miller Lee E. , Pandarinath Chethan 
Published: December 2021

AbstractObjectiveTo study the neural control of movement, it is often necessary to estimate how muscles are activated across a variety of behavioral conditions. However, estimating the latent command signal that underlies muscle activation is challenging due to its complex relation with recorded electromyographic (EMG) signals. Common approaches estimate muscle activation independently for each channel or require manual tuning of model hyperparameters to optimally preserve behaviorally-relevant features.ApproachHere, we adapted AutoLFADS, a large-scale, unsupervised deep learning approach originally designed to de-noise cortical spiking data, to estimate muscle activation from multi-muscle EMG signals. AutoLFADS uses recurrent neural networks (RNNs) to model the spatial and temporal regularities that underlie multi-muscle activation.Main ResultsWe first tested AutoLFADS on muscle activity from the rat hindlimb during locomotion, and found that it dynamically adjusts its frequency response characteristics across different phases of behavior. The model produced single-trial estimates of muscle activation that improved prediction of joint kinematics as compared to low-pass or Bayesian filtering. We also tested the generality of the approach by applying AutoLFADS to monkey forearm muscle activity from an isometric task. AutoLFADS uncovered previously uncharacterized high-frequency oscillations in the EMG that enhanced the correlation with measured force compared to low-pass or Bayesian filtering. The AutoLFADS-inferred estimates of muscle activation were also more closely correlated with simultaneously-recorded motor cortical activity than other tested approaches.SignificanceUltimately, this method leverages both dynamical systems modeling and artificial neural networks to provide estimates of muscle activation for multiple muscles that can be used for further studies of multi-muscle coordination and its control by upstream brain areas.
A nickase Cas9 gene-drive system promotes super-Mendelian inheritance in Drosophila
Authors: Del Amo Víctor López , Juste Sara Sanz , Gantz Valentino M. 
Published: December 2021

ABSTRACTCRISPR-based gene-drive systems have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance towards super-Mendelian rates (>50%). Current technologies employ a Cas9 that introduces DNA double-strand breaks into the opposing wildtype allele to replace it with a copy of the gene drive allele via DNA homology-directed repair. Yet, the use of different Cas9s versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a novel gene-drive approach that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that generating 5’ overhangs in the system yields efficient allelic conversion. The nickase gene-drive arrangement produces large, stereotyped deletions that are advantageous for targeting essential genes. Indeed, our nickase approach should expand the repertoire for gene-drive designs aimed at applications in mosquitoes and beyond.
Detection of allele-specific expression in spatial transcriptomics with spASE
Authors: Zou Luli S. , Zhao Tongtong , Cable Dylan M. , Murray Evan , Aryee Martin J. , Chen Fei , Irizarry Rafael A. 
Published: December 2021

AbstractAllele-specific expression (ASE), or the preferential expression of one allele, can be observed in transcriptomics data from early development throughout the lifespan. However, the prevalence of spatial and cell type-specific ASE variation remains unclear. Spatial transcriptomics technologies permit the study of spatial ASE patterns genome-wide at near-single-cell resolution. However, the data are highly sparse, and confounding between cell type and spatial location present further statistical challenges. Here, we introduce spASE (https://github.com/lulizou/spase), a computational framework for detecting spatial patterns in ASE within and across cell types from spatial transcriptomics data. To tackle the challenge presented by the low signal to noise ratio due to the sparsity of the data, we implement a spatial smoothing approach that greatly improves statistical power. We generated Slide-seqV2 data from the mouse hippocampus and detected ASE in X-chromosome genes, both within and across cell type, validating our ability to recover known ASE patterns. We demonstrate that our method can also identify cell type-specific effects, which we find can explain the majority of the spatial signal for autosomal genes. The findings facilitated by our method provide new insight into the uncharacterized landscape of spatial and cell type-specific ASE in the mouse hippocampus.
Age-elevated prostaglandin E2enhances mortality to influenza infection
Authors: Chen Judy , Deng Jane C. , Zemans Rachel , Zhang Min , Peters-Golden Marc , Goldstein Daniel R. 
Published: December 2021

SummaryAging impairs the immune responses to influenza A virus (IAV), resulting in increased mortality to IAV infections in older adults. With aging, there is reduced number and impaired function of alveolar macrophages (AMs), cells critical for defense against IAV. However, factors within the aged lung that impair AMs are not fully known. Using a murine model of IAV infection, we observed that aging increased the level of prostaglandin E2(PGE2) in the bronchoalveolar lavage fluid (BALF) of aged mice compared to young mice. Blockade of the PGE2receptor EP2 in aged mice increased AM numbers and subsequently enhanced survival to IAV. Additionally, PGE2impaired the mitochondrial health of AMs. We also identified senescent type II alveolar epithelial cells (AECs) as a source of the aged-associated PGE2in the lung. Our results reveal a crosstalk between AECs and AMs, via PGE2, that compromises host defense to IAV infection with aging.
Dataset-adaptive minimizer order reduces memory usage in k-mer counting
Authors: Flomin Dan , Pellow David , Shamir Ron 
Published: December 2021

AbstractThe rapid, continuous growth of deep sequencing experiments requires development and improvement of many bioinformatics applications for analysis of large sequencing datasets, including k-mer counting and assembly. Several applications reduce RAM usage by binning sequences. Binning is done by employing minimizer schemes, which rely on a specific order of the minimizers. It has been demonstrated that the choice of the order has a major impact on the performance of the applications. Here we introduce a method for tailoring the order to the dataset. Our method repeatedly samples the dataset and modifies the order so as to flatten the k-mer load distribution across minimizers. We integrated our method into Gerbil, a state-of-the-art memory efficient k-mer counter, and were able to reduce its memory footprint by 30% - 50% for large k, with only minor increase in runtime. Our tests also showed that the orders produced by our method produced superior results when transferred across datasets from the same species, with little or no order change. This enables memory reduction with essentially no increase in runtime.
Genetic architecture of dispersal and local adaptation drives accelerating range expansions
Authors: Deshpande Jhelam N. , Fronhofer Emanuel A. 
Published: December 2021

AbstractContemporary evolution has the potential to significantly alter biotic responses to global change, including range expansion dynamics and biological invasions. However, predictive models often make highly simplifying assumptions about the genetic architecture underlying relevant traits. This can be problematic since genetic architecture defines evolvability, that is, evolutionary rates, and higher order evolutionary processes, which determine whether evolution will be able to keep up with environmental change or not. Therefore, we here study the impact of the genetic architecture of dispersal and local adaptation, two central traits of high relevance for range expansion dynamics, on the speed and variability of range expansions into an environmental gradient, such as temperature. In our theoretical model we assume that dispersal and local adaptation traits result from the products of two non-interacting gene-regulatory networks (GRNs). We compare our model to simpler quantitative genetics models and show that in the GRN model, range expansions are accelerated, faster and more variable. Increased variability implies that these evolutionary changes reduce predictability. We further find that acceleration in the GRN model is primarily driven by an increase in the rate of local adaptation to novel habitats which results from greater sensitivity to mutation (decreased robustness) and increased gene expression. Our results highlight how processes at microscopic scales, here, within genomes, can impact the predictions of large scale, macroscopic phenomena, such as range expansions, by modulating the rate of evolution.
UG/Abi: a highly diverse family of prokaryotic reverse transcriptases associated with defense functions
Authors: Mestre Mario Rodríguez , Gao Linyi , Shah Shiraz A. , López-Beltrán Adrián , González-Delgado Alejandro , Martínez-Abarca Francisco , Iranzo Jaime , Redrejo-Rodríguez Modesto , Zhang Feng , Toro Nicolás 
Published: December 2021

AbstractReverse transcriptases (RTs) are enzymes capable of synthesizing DNA using RNA as a template. Within the last few years, a burst of research has led to the discovery of novel prokaryotic RTs with diverse antiviral properties, such as DRTs (Defense-associated RTs), which belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs. In this work, we performed a systematic analysis of UG and Abi RTs, increasing the number of UG/Abi members up to 42 highly diverse groups, most of which are predicted to be functionally associated with other gene(s) or domain(s). Based on this information, we classified these systems into three major classes. In addition, we reveal that most of these groups are associated with defense functions and/or mobile genetic elements, and demonstrate the antiphage role of four novel groups. Besides, we highlight the presence of one of these systems in novel families of human gut viruses infecting members of the Bacteroidetes and Firmicutes phyla. This work lays the foundation for a comprehensive and unified understanding of these highly diverse RTs with enormous biotechnological potential.
Quinacrine binds to the kinase domain of FGFR1 and inhibits its activity
Authors: Kumar Makhan , Sarkar Angshuman 
Published: December 2021

AbstractBackgroundFGF family receptors, especially FGFR1, have been widely implicated for their potential role in the promotion of oncogenesis and chemoresistance in lung cancer. Quinacrine, an anti-malarial drug, has been widely reported to exhibit anti-neoplastic properties through the activation of p53 and simultaneous inhibition of NF-kB signaling pathways in cancer cells.MethodsThe binding of QC to FGFR1 was studied using molecular docking and molecular dynamics simulation studies. The experimental kinase activity assay for the protein was performed using a luminescence-based kinase assay. FGF-induced phosphorylation and proliferation were studied by cell counting and western blotting. Matrigel-based cell migration was conducted to assess migration activity.ResultsQC interacted with multiple residues around the kinase insert domain of FGFR1 through hydrogen bonding, hydrophobic interactions, and water bridges. The kinase activity inhibition assay demonstrated a significant reduction in FGFR1 kinase activity by QC at higher concentrations, which was further observed at the cellular level in inhibition of FGFR1 phosphorylation and proliferation by QC at higher exposure concentrations of FGF stimulated cells. These effects were further validated downstream in the FGF-induced activation of cell migration.ConclusionQC did form a stable interaction with residues of FGFR1 at another allosteric site surrounding the kinase domain, leading to inhibition of its kinase activity at higher drug concentrations. This effect was further observed at the cellular level in both acidic and basic FGF ligand-induced proliferation, phosphorylation of FGFR1, and cell migration, where a trend of significant reduction in activity was observed at higher drug concentrations.
Reduction of free-roaming cat population requires high-intensity neutering in spatial contiguity to mitigate compensatory effects
Authors: Gunther Idit , Hawlena Hadas , Azriel Lior , Gibor Dan , Berke Olaf , Klement Eyal 
Published: December 2021

AbstractWhen free-roaming in natural areas, the domestic cat (Felis silvestris catus) is ranked high among the most destructive alien species. Near human dwellings, it might risk humans, impair sanitation, and suffer from poor welfare. Cats’ popularity as companion animals complicates their population control. Thus, culling is often replaced by a fertility control method called “Trap-Neuter-Return/Release (TNR),” which is considered more humane. Despite the extensive application of TNR, a long-term controlled study was never performed to test its effectiveness. We present a uniquely designed controlled field experiment for examining TNR effectiveness. The study was performed over a twelve-year period, divided into pre-intervention, mixed- and full-intervention phases, and spanned a 20Km2urban area. Trends of cat, intact-female, and kitten counts, cat reproduction, and carcass reports were compared among study phases and areas with different neutering intensities. The cat population increased during the first two study phases and did not decline in highly neutered populations, presumably due to cat immigration. Expansion of high-intensity neutering to the entire city in the full-intervention phase (>70% neutering percentage) reversed cat population growth, reaching an annual ca. 7% reduction. This population reduction was limited by a rebound increase in cat reproduction and longevity. We conclude that cat population management by TNR should be performed in high-intensity, continuously, and in geographic contiguity to enable population reduction. To enhance management effectiveness and mitigate compensatory effects, we recommend further evaluating an integrated strategy that combines TNR with complementary methods (e.g., vital resource regulation, ill cat euthanasia, and adoption).Significance StatementThough popular companion animals, domestic cats pose numerous problems when free-roaming, including predation of wildlife, hazards to humans, impaired sanitation, and a decrease in their welfare. Thus, managing their populations is essential. The Trap-Neuter-Return method (TNR, capturing, sterilizing, returning/releasing) is widely employed for managing cat populations. However, there is a lack of long-term controlled evidence for its effectiveness. We examined the outcomes of high-intensity TNR by performing a twelve-year controlled field experiment, the largest to date. Neutering over 70% of the cats caused population decline when applied over contiguous areas. However, it was limited by a rebound increase in reproduction and survival. These findings provide a robust quantification of the limitations and the long-term effectiveness of TNR.
A Non-Canonical Function of Arabidopsis ERECTA Proteins in Gibberellin Signaling
Authors: Sarnowska Elzbieta , Kubala Szymon , Cwiek Pawel , Sacharowski Sebastian , Oksinska Paulina , Steciuk Jaroslaw , Zaborowska Magdalena , Szurmak Jakub M. , Dubianski Roman , Maassen Anna , Stachowiak Malgorzata , Huettel Bruno , Ciesla Monika , Kogut Klaudia , Rolicka Anna T. , Alseekh Saleh , Bucior Ernest , Franzen Rainer , Klepacz Anna , Domagalska Malgorzata A. , Amar Samija , Siedlecki Janusz A. , Fernie Alisdair R. , Davis Seth J. , Sarnowski Tomasz J. 
Published: December 2021

AbstractThe Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs), comprising ERECTA (ER), ERECTA-LIKE 1 (ERL1) and ERECTA-LIKE 2 (ERL2), control epidermal patterning, inflorescence architecture, stomata development, and hormonal signaling. Here we show that the er/erl1/erl2 triple mutant exhibits impaired gibberellin (GA) biosynthesis and perception alongside broad transcriptional changes. ERf proteins interact in the nucleus, via kinase domains, with the SWI3B subunit of the SWI/SNF chromatin remodeling complex (CRCs). The er/erl1/erl2 triple mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin structure. The ER kinase phosphorylates SWI3B in vitro, and the inactivation of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. Correlation between DELLA overaccumulation and SWI3B proteasomal degradation together with the physical interaction of SWI3B with DELLA proteins explain the lack of RGA accumulation in the GA- and SWI3B-deficient erf mutant plants. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1) DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA receptors. Thus, the involvement of ERf proteins in transcriptional control of gene expression, and observed similar features for human HER2 (Epidermal Growth Family Receptor-member), indicate an exciting target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane receptors.ONE SENTENCE SUMMARYERECTA leucine-rich receptor-like kinase and SWI3B subunit of SWI/SNF chromatin remodeling complex cooperate in direct transcriptional control of GID1 genes in Arabidopsis.
Simultaneous Super-Resolution and Distortion Correction for Single-shot EPI DWI using Deep Learning
Authors: Ye Xinyu , Wang Peipei , Li Sisi , Zhang Jieying , Lian Yuan , Zhang Yajing , Lu Jie , Guo Hua 
Published: December 2021

AbstractSingle-shot echo planer imaging (SS-EPI) is widely used for clinical Diffusion-weighted magnetic resonance imaging (DWI) acquisitions. However, due to the limited bandwidth along the phase encoding direction, the obtained images suffer from distortion and blurring, which limits its clinical value for diagnosis. Here we proposed a deep learning-based image-quality-transfer method with a novel loss function with improved network structure to simultaneously increase the resolution and correct distortions for SS-EPI. We proposed a modified network structure based on Generative Adversarial Networks (GAN). A dense net with gradient map guidance and a multi-level fusion block was employed as the generator to suppress the over-smoothing effect. We also proposed a fractional anisotropy (FA) loss to exploit the intrinsic signal relations in DWI. In-vivo brain DWI data were used to test the proposed method. The results showed that the distortion-corrected high-resolution DWI images with restored anatomical details can be obtained from low-resolution SS-EPI images by taking the advantage of high-resolution anatomical images. Additionally, the proposed FA loss can improve the image quality and quantitative accuracy of diffusion metrics by utilizing the intrinsic relations among different diffusion directions.
ABC Transporters are billion-year-old Maxwell Demons
Authors: Flatt Solange , Busiello Daniel M. , Zamuner Stefano , De Los Rios Paolo 
Published: December 2021

ABSTRACTABC transporters are a broad family of biological machines, found in most prokaryotic and eukaryotic cells, performing the crucial import or export of substrates through both plasma and organellar membranes, and maintaining a steady concentration gradient driven by ATP hydrolysis. Building upon the present biophysical and biochemical characterization of ABC transporters, we propose here a model whose solution reveals that these machines are an exact molecular realization of the Maxwell Demon, a century-old abstract device that uses an energy source to drive systems away from thermodynamic equilibrium. In particular, the Maxwell Demon does not perform any direct mechanical work on the system, but simply selects which spontaneous processes to allow and which ones to forbid based on information that it collects and processes. In the molecular model introduced here, the different information-processing steps that characterize Maxwell Demons (measurement, feedback and resetting) are features that emerge from the biochemical and structural properties of ABC transporters, allowing us to develop an explicit bridge between the molecular level description and the higher-level language of information theory.
Nontraditional lenders and access to local agricultural credit markets by beginning and female farmers
Authors: Nadolnyak Denis , Hartarska Valentina 
Published: December 2021

PurposeThe purpose of this study is to evaluate if access to local branch infrastructure of the farm credit system institutions (FCS), banks and credit unions (BCU), and alternative financial services (AFS) providers is related to the use of credit from non-traditional lenders (NTLs). The focus is on beginning and women operators who are typically credit constrained and thus more likely to suffer from closures of bank branches and consolidation of traditional agricultural lenders.Design/methodology/approachInformed by Detragiache et al. (2000), the authors specify farmers’ use of loans as a function of their access to credit (measured by the branch density of each lender type) along with operator’s and operation’s controls. The measures of loans by NTLs (number, use, share and lender type) require the use of Poisson, Probit, Tobit and Multinomial Logit techniques. This study utilizes individual producer data from the 2018 Agricultural Resource Management Survey and 2018 county-level branch density data for FCS, BCU and AFS providers.FindingsAccess to credit from FCS is helpful to BFRs only, while access to AFS is associated with the use of loans from NTLs by women but not by BFRs. As expected, access to BCU credit matters for the use of loans from NTLs, with a complementary effect for BFRs but a substitution effect for women’s use of such loans.Originality/valueThere are no studies on local agricultural credit markets in the US that evaluate the implications from changes in access to credit on credit-constrained borrowers and their use of NTLs’ credit.