bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maize (Zea mays L.) nucleoskeletal proteins regulate nuclear envelope remodeling and function in stomatal complex development and pollen viability
Authors: McKenna JF , Gumber HK , Turpin ZM , Jalovec AM , Kartick AC , Graumann K , Bass HW 
Published: December 2020

ABSTRACTIn eukaryotes, the nuclear envelope (NE) encloses chromatin and separates it from the rest of the cell. The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex physically bridges across the NE, linking nuclear and cytoplasmic components. In plants, these LINC complexes are beginning to be ascribed roles in cellular and nuclear functions, including chromatin organization, regulation of nuclei shape and movement, and cell division. Homologs of core LINC components, KASH and SUN proteins, have previously been identified in maize. Here, we characterized the presumed LINC-associated maize nucleoskeletal proteins NCH1 and NCH2, homologs of members of the plant NMCP/CRWN family, and MKAKU41, homologous to AtKAKU4. All three proteins localized to the nuclear periphery when transiently and heterologously expressed as fluorescent protein fusions inNicotiana benthamiana. Overexpression of MKAKU41 caused dramatic changes in the organization of the nuclear periphery, including nuclear invaginations that stained positive for non-nucleoplasmic markers of the inner and outer NE, and the ER. The severity of these invaginations was altered by changes in LINC connections and the actin cytoskeleton. In maize, MKAKU41 appeared to share genetic functions with other LINC components, including control of nuclei shape, stomatal complex development, and pollen viability. Overall, our data show that NCH1, NCH2, and MKAKU41 have characteristic properties of LINC-associated plant nucleoskeletal proteins, including interactions with NE components suggestive of functions at the nuclear periphery that impact the overall nuclear architecture.
A test of the hypothesis that variable mutation rates create signals that have previously been interpreted as evidence of archaic introgression into humans
Authors: Amos William 
Published: December 2020

AbstractIt is widely accepted that non-African humans carry 1-2% Neanderthal DNA due to historical inter-breeding. However, inferences about introgression rely on a critical assumption that mutation rate is constant and that back-mutations are too rare to be important. Both these assumptions have been challenged, and recent evidence points towards an alternative model where signals interpreted as introgression are driven mainly by higher mutation rates in Africa. In this model, non-Africans appear closer to archaics not because they harbour introgressed fragments but because Africans have diverged more. Here I test this idea by using the density of rare, human-specific variants (RHSVs) as a proxy for recent mutation rate. I find that sites that contribute most to the signal interpreted as introgression tend to occur in tightly defined regions spanning only a few hundred bases in which mutation rate differs greatly between the two human populations being compared. Mutation rate is invariably higher in the population into which introgression isnotinferred. I confirmed that RHSV density reflects mutation rate by conducting a parallel analysis looking at the density of RHSVs around sites with three alleles, an independent class of site that also requires recurrent mutations to form. Near-identical peaks in RHSV density are found, suggesting a common cause. Similarly, coalescent simulations confirm that, with constant mutation rate, introgressed fragments do not occur preferentially in regions with a high density of rare, human-specific variants. Together, these observations are difficult to reconcile with a model where excess base-sharing is driven by archaic legacies but instead provide support for a higher mutation rate inside Africa driving increased divergence from the ancestral human state.
Motor guidance by long-range communication through the microtubule highway
Authors: Wijeratne Sithara S. , Fiorenza Shane A. , Subramanian Radhika , Betterton Meredith D. 
Published: December 2020

AbstractCoupling of motor proteins within arrays drives muscle contraction, flagellar beating, chromosome segregation, and other biological processes. Current models of motor coupling invoke either direct mechanical linkage or protein crowding, which rely on short-range motor-motor interactions. In contrast, coupling mechanisms that act at longer length scales remain largely unexplored. Here we report that microtubules can physically couple motor movement in the absence of short-range interactions. The human kinesin-4 Kif4A changes the run-length and velocity of other motors on the same microtubule in the dilute binding limit, when 10-nm-sized motors are separated by microns. This effect does not depend on specific motor-motor interactions because similar changes in Kif4A motility are induced by kinesin-1 motors. A micron-scale attractive interaction potential between motors is sufficient to recreate the experimental results in a computational model. Unexpectedly, our theory suggests that long-range microtubule-mediated coupling not only affects binding kinetics but also motor mechanochemistry. Therefore, motors can sense and respond to motors bound several microns away on a microtubule. These results suggest a paradigm in which the microtubule lattice, rather than being merely a passive track, is a dynamic medium responsive to binding proteins to enable new forms of collective motor behavior.
Genetic architecture of transmission stage production and virulence in schistosome parasites
Authors: CLEC’H Winka LE , Chevalier Frédéric D. , McDew-White Marina , Menon Vinay , Arya Grace-Ann , Anderson Timothy J.C. 
Published: December 2020

ABSTRACTBoth theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood flukeSchistosoma mansonishows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence toBiomphalaria glabratasnail hosts, and determined four-week cercarial shedding profiles in F0, F1 and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs. These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.
A novel deep-sea bacterial threonine dehydratase drives cysteine desulfuration and hydrogen sulfide production
Authors: Ma Ning , Sun Yufan , Zhang Wen , Sun Chaomin 
Published: December 2020

ABSTRACTCysteine desulfuration is one of the main ways for hydrogen sulfide (H2S) generation in cells and is usually conducted by cystathionine γ-lyase. Herein, we describe a newly discovered deep-sea bacterial threonine dehydratase (psTD), which is surprisingly discovered to drive L-cysteine desulfuration. The mechanisms of psTD catalyzing cysteine desulfuration towards H2S production are first clarifiedin vitroandin vivothrough a combination of genetic and biochemical methods. Furthermore, based on the solved structures of psTD and its various mutants, two or three pockets are found in the active site of psTD, and switch states between inward and outward orientation of a key amino acid R77 determine the open or close status of Pocket III for small molecule exchanges, which further facilitates cysteine desulfuration. Our results reveal the functional diversity and structural specificity of psTD towards L-cysteine desulfuration and H2S formation. Given the broad distribution of psTD homologs in different bacteria, we speculate that some threonine dehydratases have evolved a novel function towards cysteine desulfuration, which benefits the producer to utilize cysteine as a sulfur source for better adapting external environments.
Functional Characterization of a Lassa Virus Fusion Inhibitors Adaptive Mutant
Authors: Guo Jiao , Zhang Guangshun , Liu Yang , Cao Junyuan , Zhang Mengmeng , Lan Xiaohao , Zhang Yueli , Liu Chenchen , Xiao Gengfu , Wang Wei 
Published: December 2020

ABSTRACTLassa virus (LASV) glycoprotein complex (GPC) contains retained stable-signal peptide (SSP), GP1, and GP2. SSP interacts with GP2 and provides an interface targeted by numerous fusion inhibitors. Serially passaging of LASV with inhibitors allowed some adaptive mutants to be obtained of which most had mutations located in the transmembrane (TM) domain of GP2. In the current study, we focused on the F446L mutant, which is reported to confer resistance to ST-series inhibitors. We found that F446L conferred cross-resistance to structurally distinct inhibitors. Furthermore, F446L increased the fusion activities of LASV and Mopeia virus GPC, elevating the pH threshold for fusion of LASV and promoting fusion of MOPV at neutral pH. F446L exerted little effect on the pseudotype viral growth profile or thermostability. By introducing other residues to the conserved F446 locus, it was found that this site was less compatible with a similar tyrosine residue and was intolerable to charged residues. These results help characterize the fusion inhibitor target located in the TM domain of GP2, which should be useful for drug and vaccine design.IMPORTANCEThe LASV SSP-GP2 interface provides an Achilles heel that is targeted by numerous inhibitors. However, the emergence of resistant viruses is a major concern for direct antiviral drugs. In this study, we investigated the F446L mutant located in the GPC TM domain to determine the relationship between drug resistance, membrane fusion activity, viral growth kinetics, and thermostability. These results will be helpful in monitoring drug-resistant variants, as well as the advancement of drug and vaccine design.
Periscope Proteins are variable length regulators of bacterial cell surface interactions
Authors: Whelan Fiona , Lafita Aleix , Gilburt James , Dégut Clément , Griffiths Samuel C. , Jenkins Huw T. , St John Alexander N. , Paci Emanuele , Moir James W.B. , Plevin Michael J. , Baumann Christoph G. , Bateman Alex , Potts Jennifer R. 
Published: December 2020

AbstractChanges at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly-available long-read genome sequencing data, we propose this new class could contain over 50 distinct proteins, including those implicated in host colonisation and biofilm formation by human pathogens. In large multi-domain proteins, sequence divergence between adjacent domains appears to reduce inter-domain misfolding. Periscope Proteins break this “rule”, suggesting their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria and the immune system.
DeepImmuno: Deep learning-empowered prediction and generation of immunogenic peptides for T cell immunity
Authors: Li Guangyuan , Iyer Balaji , Prasath V. B. Surya , Ni Yizhao , Salomonis Nathan 
Published: December 2020

ABSTRACTT-cells play an essential role in the adaptive immune system by seeking out, binding and destroying foreign antigens presented on the cell surface of diseased cells. An improved understanding of T-cell immunity will greatly aid in the development of new cancer immunotherapies and vaccines for life threatening pathogens. Central to the design of such targeted therapies are computational methods to predict non-native epitopes to elicit a T cell response, however, we currently lack accurate immunogenicity inference methods. Another challenge is the ability to accurately simulate immunogenic peptides for specific human leukocyte antigen (HLA) alleles, for both synthetic biological applications and to augment real training datasets. Here, we proposed a beta-binomial distribution approach to derive epitope immunogenic potential from sequence alone. We conducted systematic benchmarking of five traditional machine learning (ElasticNet, KNN, SVM, Random Forest, AdaBoost) and three deep learning models (CNN, ResNet, GNN) using three independent prior validated immunogenic peptide collections (dengue virus, cancer neoantigen and SARS-Cov-2). We chose the CNN model as the best prediction model based on its adaptivity for small and large datasets, and performance relative to existing methods. In addition to outperforming two highly used immunogenicity prediction algorithms, DeepHLApan and IEDB, DeepImmuno-CNN further correctly predicts which residues are most important for T cell antigen recognition. Our independent generative adversarial network (GAN) approach, DeepImmuno-GAN, was further able to accurately simulate immunogenic peptides with physiochemical properties and immunogenicity predictions similar to that of real antigens. We provide DeepImmuno-CNN as source code and an easy-to-use web interface.Data AvailabilityDeepImmuno Python3 code is available at https://github.com/frankligy/DeepImmuno. The DeepImmuno web portal is available from https://deepimmuno.herokuapp.com. The data in this article is available in GitHub and supplementary materials.
Multi-class Cancer Classification and Biomarker Identification using Deep Learning
Authors: Muazzam Fariha 
Published: December 2020

AbstractGenetic data is important for analysing cellular functions whose disruption gives rise to various kinds of cancer. The intricacies of gene interaction are captured in various kinds of data for cancer detection through sequencing technology, but diagnosis, prognosis and treatment are still hard. Advent of machine learning helped researchers in supervised and unsupervised learning tasks along with gene identification but resourcefulness has not been overtly satisfactory. This research revolves around multi-class cancer classification, feature extraction and relevant gene identification through deep learning methods for 12 different types of cancers using RNA-SEQ from The Cancer Genome Atlas.It has been constrained by hardware resource availability and within them the experiments that have been performed have shown promising results. Stacked De-noising Autoencoders were used for feature extraction and biomarker identification while 1D Convolutional Neural Networks for classification. Classification was performed with extracted features and relevant genes, which gave average performance of around 94% and 95% respectively. We were able to identify generic cancer-related pathways and their associated genes through Stacked De-noising Auto-encoders generated weight matrix and features. The common pathways include WNT Signalling Pathway, Angiogenesis. Moreover, across all pathways some recurrent genes were observed, namely: PIK3C2G, PCDHB8, WNT10A and these genes were found, in literature, to be involved in multiple types of cancer.The proposed approach shows superior performance and promise against traditional techniques used by bioinformatics community, in terms of accuracy and relevant gene identification.
Amyloid Beta Oligomers Prevents Lysosomal Targeting of miRNP to Stop Its Recycling and Target Cytokine Repression in Glial Cells
Authors: De Dipayan , Bhattacharyya Suvendra N. 
Published: December 2020

AbstractmRNAs encoding inflammatory cytokines are targeted by miRNAs and remain repressed in neuroglial cells. On exposure to amyloid beta 1-42 oligomers, glial cells start expressing proinflammatory cytokines although there has been increase in repressive miRNAs levels as well. Exploring the mechanism of this potential immunity of target cytokine mRNAs against repressive miRNAs in amyloid beta exposed glial cells, we have identified differential compartmentalization of repressive miRNAs in glial cells to explain this aberrant miRNA function. While the target mRNAs were found to be associated with polysomes attached to endoplasmic reticulum, the miRNPs found to be present predominantly with endosomes that failed to recycle to endoplasmic reticulum attached polysomes to repress mRNA targets in treated cells. Amyloid beta oligomers, by masking the Rab7 proteins on endosomal surface, affects Rab7 interaction with Rab Interacting Lysosomal Protein (RILP) on lysosomes to restrict endosomal maturation and its lysosomal targeting. This causes retarded miRNP targeting to lysosomes and recycling. Similar defects in miRNP retrieval has been observed in endosome maturation defective cells depleted for RILP or treated with Bafilomycin. RNA processing body localization of the miRNPs was also noted in treated cells that happens as a consequence of enhanced endosomal retention of miRNPs. Interestingly, depletion of P-body partly rescues the miRNA function in glial cells exposed to amyloid beta and restricts the excess cytokine expression there.Graphical AbstractKey PointsAmyloid beta exposure causes accumulation of inactive miR-146 miRNP to cause elevated proinflammatory cytokine production in glial cells.Amyloid beta masks Rab7-RILP interaction to reduce endosome lysosome interaction.Accumulated miRNPs failed to get targeted to lysosomes in amyloid exposed cells due to loss of endosome lysosome interactionLysosomal compartmentalization of miRNPs is required for its recycling and repression ofde novotargetsAccumulated miRNPs are stored in P-Bodies and depletion of P-Bodies rescues miRNA function in amyloid exposed glial cells.
How our homes impact our health: using a COVID-19 informed approach to examine urban apartment housing
Authors: Peters Terri , Halleran Anna 
Published: December 2020

PurposeThe COVID-19 global health crisis is undeniably a global housing crisis. Our study focuses on quality of life in urban mid- and high-rise apartment housing, the fastest growing housing types in many cities around the world. This housing typology presents unique challenges relating to connection to nature, daylight and fresh air.Design/methodology/approachThis multi-disciplinary literature review analyzes more than 100 published papers from peer-reviewed sources from environmental psychology, building science and architecture relevant to quality of life in high-rise housing, as well as more than 40 recent newspaper and magazine articles about the possible impacts of COVID-19 on housing. We identify synergies between passive design strategies and health-promoting architecture or “restorative environmental design” principles.FindingsPost-pandemic, health-promoting apartment housing design must prioritize (1) window placement and views that support stress recovery and restoration; (2) lighting levels based on spaces that can satisfy multiple uses and users; (3) bedrooms designed for restful sleep that contribute to circadian regulation; (4) living rooms with better indoor air quality, with a focus on natural ventilation; (5) access to nature, through the purposeful design of balconies and (6) unit sizes and layouts that enable physical distancing and prevent crowding.Originality/valueWe identify new social and environmental design priorities in the form of evidence-based design principles to inform and promote healthy and restorative living environments for residents in apartment housing.
How should beef be produced? Consumer expectations and views on local beef production in South Tyrol (Italy)
Authors: Kühl Sarah , Busch Gesa , Gauly Matthias 
Published: December 2020

PurposeLocal origin of meat acts as a key quality indicator for consumers. How an ideal local meat production should look like is rather unknown. The purpose of this study is to comprehensively analyse how an ideal local beef production should be constituted.Design/methodology/approach432 consumers from a North Italian province (South Tyrol) were questioned online about their views regarding (local) beef production. 12 attributes, from calf rearing to transport times, were presented with different options. Participants selected the most ideal options from their perspective. Further, willingness to pay for local beef and for the ideally produced local beef as well as the importance of local production for different food categories were assessed.FindingsThe results are quite heterogeneous but show that local production is especially of importance for eggs, dairy products and beef. Traceability to the farms, daily access to a paddock and access to pasture during summer, silage-free feeding, low transport times and suckler cow husbandry are aspects that are mostly selected as ideal. A price premium of 35% for locally produced beef and up to 50% for this ideal production seems reasonable for most consumers.Research limitations/implicationsThe study only includes South Tyrolean consumers and thus the validity is limited to this area. Although transferability to other regions can be assumed, future studies are necessary to confirm this assumption.Originality/valueThis is the first study analysing consumers expectations towards local beef production considering several production levels.
Fun in the workplace and employee turnover: is less managed fun better?
Authors: Tews Michael J. , Jolly Phillip M. , Stafford Kathryn 
Published: December 2020

PurposeDespite previous research indicating that fun in the workplace has favorable outcomes, the effect of fun on turnover has not been definitively determined. The present study analyzed the direct effects on turnover of three dimensions of fun: fun activities, coworker socializing and manager support for fun, and the moderating influence of managed fun (e.g. whether fun is perceived as contrived).Design/methodology/approachLogistic regression was used to analyze the fun in the workplace-turnover relationship with a sample of 491 hourly associates from 141 stores of a US national retailer. Data on the fun were obtained through surveys that were paired with turnover data collected six months afterward from corporate records.FindingsFun activities were only found to be associated with a lower turnover when employees perceived fun as less managed. When employees perceived fun as more managed, fun activities had no effect on turnover. Coworker socializing was associated with a lower turnover when fun was perceived as less managed and higher turnover when fun was perceived as more managed.Research limitations/implicationsAs the data were obtained from employees from one organization, further research would be valuable with additional samples to substantiate the generalizability of the results.Practical implicationsGiven the challenge of turnover and the increasing prevalence of efforts to promote fun in the workplace, organizations should allow fun activities to be less managed (and thus more organic) to help reduce turnover.Originality/valueWhile previous research has addressed managed/less managed fun in qualitative research, the present study represents the first investigation to examine this aspect of fun in the workplace from a quantitative perspective and to examine its relationship with employee turnover.