bluuebunny/crossref_metadata_2025_split huggingface dataset:
How effective are face coverings in reducing transmission of COVID-19?
Authors: Robinson Joshua F. , de Anda Ioatzin Rios , Moore Fergus J. , Gregson Florence K. A. , Reid Jonathan P. , Husain Lewis , Sear Richard P. , Royall C. Patrick 
Published: December 2020

In the COVID–19 pandemic, among the more controversial issues is the use of face coverings. To address this we show that the underlying physics ensures particles with diameters ≳1 µm are efficiently filtered out by a simple cotton or surgical mask. For particles in the submicron range the efficiency depends on the material properties of the masks, though generally the filtration efficiency in this regime varies between 30 to 60 % and multi-layered cotton masks are expected to be comparable to surgical masks.Respiratory droplets are conventionally divided into coarsedroplets(≳5–10 µm) responsible fordroplet transmissionandaerosols(≳ 5–10 µm) responsible forairborne transmission. Masks are thus expected to be highly effective at preventing droplet transmission, with their effectiveness limited only by the mask fit, compliance and appropriate usage. By contrast, knowledge of the size distribution of bioaerosols and the likelihood that they contain virus is essential to understanding their effectiveness in preventing airborne transmission. We argue from literature data on SARS-CoV-2 viral loads that the finest aerosols (≳ 1 µm) are unlikely to contain even a single virion in the majority of cases; we thus expect masks to be effective at reducing the risk of airborne transmission in most settings.
Diagnosis of SARS-CoV-2 infections in times of material shortage
Authors: Sandri Thaisa Lucas , Inoue Juliana , Geiger Johanna , Griesbaum Johanna-Marie , Heizel Constanze , Burnet Michael , Fendel Rolf , Kremsner Peter G. , Held Jana , Kreidenweiss Andrea 
Published: December 2020

AbstractThe pandemic caused by SARS-CoV-2 resulted in increasing demands for diagnostic tests, leading to a shortage of recommended testing materials and reagents. This study reports on the performance of self-sampled alternative swabbing material (ordinary Q-tips tested against flocked swab and rayon swab), of reagents for classical RNA extraction (phenol/guanidine-based protocol against a commercial kit), and of intercalating dye-based one-step quantitative reverse transcription real-time PCRs (RT-qPCR) compared against the gold standard hydrolysis probe-based assays for SARS-CoV-2 detection. The study found sampling with Q-tips, RNA extraction with classical protocol and intercalating dye-based RT-qPCR as a reliable and comparably sensitive strategy for detection of SARS-CoV-2 - particularly valuable in the current period with a resurgent and dramatic increase in SARS-CoV-2 infections and growing shortage of diagnostic materials as well for regions limited in resources.
Estimating population size when individuals are asynchronous: a model illustrated with northern elephant seal breeding colonies
Authors: Condit Richard , Allen Sarah G. , Costa Daniel P. , Codde Sarah , Goley P. Dawn , Le Boeuf Burney J. , Lowry Mark S. , Morris Patricia 
Published: December 2020

AbstractOur aim was to develop a method for estimating the number of animals using a single site in an asynchronous species, meaning that not all animals are present at once so that no one count captures the entire population. This is a common problem in seasonal breeders, and in northern elephant seals, we have a model for quantifying asynchrony at the Año Nuevo colony. Here we test the model at several additional colonies having many years of observations and demonstrate how it can account for animals not present on any one day. This leads to correction factors that yield total population from any single count throughout a season. At seven colonies in California for which we had many years of counts of northern elephant seals, we found that female arrival date varied < 2 days between years within sites and by < 5 days between sites. As a result, the correction factor for any one day was consistent, and at each colony, multiplying a female count between 26 and 30 Jan by 1.15 yielded an estimate of total population size that minimized error. This provides a method for estimating the female population size at colonies not yet studied. Our method can produce population estimates with minimal expenditure of time and resources and will be applicable to many seasonal species with asynchronous breeding phenology, particularly colonial birds and other pinnipeds. In elephant seals, it will facilitate monitoring the population over its entire range.
PISCES: a package for rapid quantitation and quality control of large scale mRNA-seq datasets
Authors: Shirley Matthew D. , Radhakrishna Viveksagar K. , Golji Javad , Korn Joshua M. 
Published: December 2020

AbstractPISCES eases processing of large mRNA-seq experiments by encouraging capture of metadata using simple textual file formats, processing samples on either a single machine or in parallel on a high performance computing cluster (HPC), validating sample identity using genetic fingerprinting, and summarizing all outputs in analysis-ready data matrices. PISCES consists of two modules: 1) compute cluster-aware analysis of individual mRNA-seq libraries including species detection, SNP genotyping, library geometry detection, and quantitation using salmon, and 2) gene-level transcript aggregation, transcriptional and read-based QC, TMM normalization and differential expression analysis of multiple libraries to produce data ready for visualization and further analysis.PISCES is implemented as a python3 package and is bundled with all necessary dependencies to enable reproducible analysis and easy deployment. JSON configuration files are used to build and identify transcriptome indices, and CSV files are used to supply sample metadata and to define comparison groups for differential expression analysis using DEseq2. PISCES builds on many existing open-source tools, and releases of PISCES are available onGitHubor the python package index (PyPI).
Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson’s disease models
Authors: de Rus Jacquet Aurélie , Ambaw Abeje , Tambe Mitali Arun , Ma Sin Ying , Timmers Michael , Grace Mary H. , Wu Qing-Li , Simon James E. , McCabe George P. , Lila Mary Ann , Shi Riyi , Rochet Jean-Christophe 
Published: December 2020

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease’s motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.Graphical AbstractThe isoflavone-rich extracts red clover and soy and the individual isoflavones daidzein and equol protect neuronal cultures against environmental and genetic triggers of Parkinson’s disease, and rescue motor deficits in rats exposed to the neurotoxin 6-OHDA.
Fluorescent protein expression as a proxy of bacterial fitness in a high throughput assay
Authors: Schlechter Rudolf O , Kear Evan J , Remus Daniela M , Remus-Emsermann Mitja NP 
Published: December 2020

AbstractBacterial growth is classically assessed by measuring the increase in optical density of pure cultures in shaken liquid media. Measuring growth using optical density has severe limitations when studying multistrain interactions as it is not possible to measure the growth of individual strains within mixed cultures. Here we demonstrated that constitutively expressed fluorescent proteins can be used to track the growth of individual strains in different liquid media. Fluorescence measurements were highly correlated with optical density measurements and cell counts. This allowed us to assess bacterial growth not only in pure cultures, but also in mixed bacterial cultures and determine the impact of competitors on a focal strain, thereby assessing relative fitness. Furthermore, we were able to track the growth of two different strains simultaneously by using fluorescent proteins with differential excitation and emission wavelengths. Bacterial densities measured by fluorescence yielded more consistent data between technical replicates than optical density measurements. Our setup employs fluorescent microplate readers that allow for high throughput and replication.ImportanceWe expand on an important limitation of the concept of measuring bacterial growth which is classically limited to one strain at a time. By adopting this approach, it is possible to measure growth of several bacterial strains simultaneously in high temporal resolution and in a high throughput manner. This is important to investigate bacterial interactions such as competition and facilitation.
A multi-omics dataset for the analysis of Frontotemporal Dementia genetic subtypes
Authors: Menden Kevin , Francescatto Margherita , Nyima Tenzin , Blauwendraat Cornelis , Dhingra Ashutosh , Castillo-Lizardo Melissa , Fernandes Noémia , Kaurani Lalit , Kronenberg-Versteeg Deborah , Atasu Burcu , Sadikoglou Eldem , Borroni Barbara , Rodriguez-Nieto Salvador , Simon-Sanchez Javier , Fischer Andre , Craig David Wesley , Neumann Manuela , Bonn Stefan , Rizzu Patrizia , Heutink Peter 
Published: December 2020

AbstractUnderstanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated a multi-omics dataset for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. Here, we present multi-omics datasets generated from the frontal lobe of post-mortem human brain tissue from patients with mutations in MAPT, GRN and C9orf72 and healthy controls. This data resource consists of four datasets generated with different technologies to capture the transcriptome by RNA-seq, and small RNA-seq, and supplemented this date with CAGE-seq, and methylation profiling. We show concrete examples on how to use the resulting data and confirm current knowledge about FTD and identify new processes for further investigation. This extensive multi-omics dataset holds great value to reveal new research avenues for this devastating disease.
Prediction of Michaelis constants from structural features using deep learning
Authors: Kroll Alexander , Heckmann David , Lercher Martin J. 
Published: December 2020

ABSTRACTThe Michaelis constantKMdescribes the affinity of an enzyme for a specific substrate, and is a central parameter in studies of enzyme kinetics and cellular physiology. As measurements ofKMare often difficult and time-consuming, experimental estimates exist for only a minority of enzyme-substrate combinations even in model organisms. Here, we build and train an organism-independent model that successfully predictsKMvalues for natural enzyme-substrate combinations using machine and deep learning methods. Predictions are based on a task-specific molecular fingerprint of the substrate, generated using a graph neural network, and the domain structure of the enzyme. Model predictions can be used to estimate enzyme efficiencies, to relate metabolite concentrations to cellular physiology, and to fill gaps in the parameterization of kinetic models of cellular metabolism.
HLA-E restricted, HIV-1 suppressing, Gag specific CD8+ T cells offer universal vaccine opportunities
Authors: Yang Hongbing , Rei Margarida , Brackenridge Simon , Brenna Elena , Sun Hong , Abdulhaqq Shaheed , Liu Michael K P , Ma Weiwei , Kurupati Prathiba , Xu Xiaoning , Cerundolo Vincenzo , Jenkins Edward , Davis Simon J. , Sacha Jonah B. , Früh Klaus , Picker Louis J. , Borrow Persephone , Gillespie Geraldine , McMichael Andrew J. 
Published: December 2020

AbstractHuman leukocyte antigen-E (HLA-E) normally presents a HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus vectored simian immunodeficiency virus (SIV) vaccine, generated Mamu-E (HLA-E homolog) restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, human immunodeficiency virus type 1 (HIV-1) specific HLA-E restricted T cells have not been observed in HIV-1-infected individuals. Here we primed HLA-E restricted HIV-1 specific CD8+ T cellsin vitro.These T cell clones, and allogeneic CD8+ T cells transduced with their T cell receptors, suppressed HIV-1 replication in CD4+ T cellsin vitro. Vaccine induction of efficacious HLA-E restricted HIV-1 specific T cells should therefore be possible.One Sentence SummaryCD8+T cells that recognize a Gag peptide presented by HLA-E suppress HIV-1 replicationin vitro.
Strong selective environments determine evolutionary outcome in time-dependent fitness seascapes
Authors: Cairns Johannes , Borse Florian , Mononen Tommi , Hiltunen Teppo , Mustonen Ville 
Published: December 2020

AbstractThe impact of fitness landscape features on evolutionary outcomes has attracted considerable interest in recent decades. However, evolution often occurs under time-dependent selection in so-called fitness seascapes where the landscape is under flux. Fitness seascapes are an inherent feature of natural environments, where the landscape changes owing both to the intrinsic fitness consequences of previous adaptations and extrinsic changes in selected traits caused by new environments. The complexity of such seascapes may curb the predictability of evolution. However, empirical efforts to test this question utilising a comprehensive set of regimes are lacking. Here we employed anin vitromicrobial model system to investigate differences in evolutionary outcomes between time-invariant and -dependent environments, including all possible temporal permutations, with three subinhibitory antimicrobials and a viral parasite (phage) as selective agents. Expectedly, time-invariant environments caused stronger directional selection for resistances compared to time-dependent environments. Intriguingly, however, multidrug resistance outcomes in both cases were largely driven by two strong selective agents (rifampicin and phage) out of four agents in total. These agents either caused cross-resistance or obscured the phenotypic effect of other resistance mutations, modulating the evolutionary outcome overall in time-invariant environments and as a function of exposure epoch in time-dependent environments. This suggests that identifying strong selective agents and their pleiotropic effects is critical for predicting evolution in fitness seascapes, with ramifications for evolutionarily informed strategies to mitigate drug resistance evolution.
Profiling of extracellular small RNAs highlights a strong bias towards non-vesicular secretion
Authors: Sork Helena , Conceicao Mariana , Corso Giulia , Nordin Joel , Lee Yi Xin Fiona , Krjutskov Kaarel , Westholm Jakub Orzechowski , Vader Pieter , Pauwels Marie , Vandenbroucke Roosmarijn , Wood Matthew JA , Andaloussi Samir EL , Mäger Imre 
Published: December 2020

ABSTRACTExtracellular environment consists of a plethora of different molecules, including extracellular miRNA that can be secreted in association with extracellular vesicles (EVs) or soluble protein complexes (non-EVs). Yet, it is generally accepted that most of the biological activity is attributed to EV-associated miRNAs. The capability of EVs to transport cargoes has attracted much interest towards developing EVs as therapeutic short RNA carriers by using endogenous loading strategies for miRNA enrichment. Here, by overexpressing miRNA and shRNA sequences of interest in source cells and using size exclusion liquid chromatography (SEC) to separate the cellular secretome into EV and non-EV fractions, we saw that strikingly, <2% of all secreted overexpressed miRNA were found in association with EVs. To see whether the prominent non-EV miRNA secretion also holds true at the basal expression level of native miRNA transcripts, both fractions were further analysed by small RNA sequencing. This revealed a global correlation of EV and non-EV miRNA abundance to that of their parent cells and showed an enrichment only for miRNAs with a relatively low cellular expression level. Further quantification showed that similarly to the transient overexpression context, an outstanding 96.2-99.9% of total secreted miRNA at its basal level was secreted to the non-EV fraction. Yet, even though EVs contain only a fraction of secreted miRNAs, these molecules were found stable at 37°C in serum-containing environment, indicating that if sufficient miRNA loading to EVs is achieved, EVs can remain miRNA delivery-competent for a prolonged period of time. This study suggests that the passive endogenous EV loading strategy can be a relatively wasteful way of loading miRNA to EVs and active miRNA loading approaches are needed for developing advanced EV miRNA therapies in the future.
HOCMO: A Tensor-based Higher-Order Correlation Model to Deconvolute Epigenetic Microenvironment in Breast Cancer
Authors: Lu Charles , Sherpa Rintsen , Klindziuk Liubou , Kriel Stefanie , Mollah Shamim 
Published: December 2020

AbstractAn in-depth understanding of epithelial breast cell response to growth-promoting ligands is required to elucidate how signals from the microenvironment affect cell-intrinsic regulatory networks and their resultant cellular phenotypes, such as cell growth, progression, and differentiation. Understanding the cellular response to these signals is particularly important in understanding the mechanisms of breast cancer initiation and progression. There is increasing evidence that aberrant epigenetic marks are present in cells of the breast tumor microenvironment and are known to affect these cellular processes. However, the mechanisms by which epigenetic microenvironment signals influence these cellular phenotypes are complex and currently not well established. To deconvolute the complexity of the epigenetic microenvironment signals in breast cancer, we developed a novel tensor-based correlation method: HOCMO (Higher-Order Correlation Model), applying to proteomics time series data to reveal the four-way regulatory dynamics among signaling proteins, histones, and growth-promoting ligands across multiple time points in the breast epithelial cells. HOCMO reveals two functional modules and the onset of specific protein-histone signatures in response to growth ligands contributing to distinct cellular phenotypes indicative of breast cancer initiation and progression. We evaluate robustness of our tensor model against baseline method TensorLy and achieved slight improvement in terms of reconstruction error and execution time. HOCMO is a data independent self-supervised learning method with superior interpretability that can capture the strength of complex interactions such as inter- and intra-pathway cellular signaling networks in any diseases or biological systems.
Postnatal persistence of sex-dependent renal developmentally programmed structural and molecular changes in nonhuman primates
Authors: Bishop Andrew C. , Spradling-Reeves Kimberly D. , Shade Robert E. , Lange Kenneth J. , Birnbaum Shifra , Favela Kristin , Dick Edward J. , Nijland Mark J. , Li Cun , Nathanielsz Peter W. , Cox Laura A. 
Published: December 2020

AbstractBackgroundPoor nutrition during development programs kidney function. No studies on postnatal consequences of decreased perinatal nutrition exist in nonhuman primates (NHP) for translation to human renal disease. Our baboon model of moderate maternal nutrient restriction (MNR) produces intrauterine growth restricted (IUGR) and programs renal fetal phenotype. We hypothesized that the IUGR phenotype persists postnatally, influencing responses to a high-fat, high-carbohydrate, high-salt (HFCS) diet.MethodsPregnant baboons ate chow (Control; CON) or 70% of control intake (MNR) from 0.16 gestation through lactation. MNR offspring were IUGR at birth. At weaning, all offspring (CON and IUGR females and males, n=3/group) ate chow. At ~4.5 years of age, blood, urine, and kidney biopsies were collected before and after a 7-week HFCS diet challenge. Kidney function, unbiased kidney gene expression, and untargeted urine metabolomics were evaluated.ResultsIUGR female and male kidney transcriptome and urine metabolome differed from CON at 3.5 years, prior to HFCS. After the challenge, we observed sex-specific and fetal exposure-specific responses in urine creatinine, urine metabolites, and renal signaling pathways.ConclusionsWe previously showed mTOR signaling dysregulation in IUGR fetal kidneys. Before HFCS, gene expression analysis indicated that dysregulation persists postnatally in IUGR females. IUGR male offspring response to HFCS showed uncoordinated signaling pathway responses suggestive of proximal tubule injury. To our knowledge, this is the first study comparing CON and IUGR postnatal juvenile NHP and the impact of fetal and postnatal life caloric mismatch. Perinatal history needs to be taken into account when assessing renal disease risk.