bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germination response of diverse wild and landrace chile peppers (Capsicumspp.) under drought stress simulated with polyethylene glycol
Authors: Bernau Vivian , Barbolla Lev Jardón , McHale Leah K. , Mercer Kristin L. 
Published: July 2020

AbstractResponses to drought within a single species may vary based on plant development stage, drought severity, and the avoidance or tolerance mechanisms employed. Early drought stress can restrict emergence and seedling growth. Thus, in areas where water availability is limited, rapid germination leading to early plant establishment may be beneficial. Alternatively, germination without sufficient water to support the seedling may lead to early senescence, so reduced germination under low moisture conditions may be adaptive at the level of the population. We studied the germination response to osmotic stress of diverse chile pepper germplasm collected in southern Mexico from varied ecozones, cultivation systems, and of named landraces. Drought stress was simulated using polyethylene glycol solutions. Overall, survival time analysis revealed delayed germination at the 20% concentration of PEG across all ecozones. The effect was most pronounced in the genotypes from hotter, drier ecozones. Additionally, accessions from wetter and cooler ecozones had the fastest rate of germination. Moreover, accessions of the landracesCosteño RojoandTustagerminated more slowly and incompletely if sourced from a drier ecozone than a wetter one, indicating that slower, reduced germination under drought stress may be an adaptive avoidance mechanism. Significant differences were also observed between named landraces, with more domesticated types from intensive cultivation systems nearly always germinating faster than small-fruited backyard- or wild-types, perhaps due to the fact that the smaller-fruited accessions have generally undergone less selection. Thus, we conclude that there is evidence of local adaptation to both ecozone of origin and source cultivation system in germination characteristics of diverse chile peppers.
In-cell detection of conformational sub-states of a GPCR quaternary structure: Modulation of sub-state probability by cognate ligand binding
Authors: Paprocki Joel , Biener Gabriel , Stoneman Michael , Raicu Valerica 
Published: July 2020

ABSTRACTWhile the notion that G protein-coupled receptors (GPCRs) associate into homo- and hetero-oligomers has gained more recognition in recent years, a lack of consensus remains among researchers regarding the functional relevance of GPCR oligomerization. A relatively recent technique, Förster resonance energy transfer (FRET) spectrometry, allows for the determination of the oligomeric (or quaternary) structure of proteins in living cells via analysis of efficiency distributions of energy transferred from optically excited fluorescent tags acting as donors of energy to fluorescent tags acting as acceptors of energy and residing within the same oligomer. In this study, we significantly improved the resolution of the FRET-spectrometry approach to detect small differences between the interprotomeric distances among GPCR oligomers with subtle differences in quaternary structures. We then used this approach to study the conformational substates of oligomers of sterile 2 α-factor receptor (Ste2), a class D GPCR found in the yeastSaccharomyces cerevisiaeof mating typea. Ste2 has previously been shown to form tetrameric oligomers at relatively low expression levels (between 11 and 140 molecules/μm2) in the absence of its cognate ligand, the α-factor pheromone. The significantly improved FRET spectrometry technique allowed us to detect multiple distinct quaternary conformational substates of Ste2 oligomers, and to assess how the α-factor ligand altered the proportion of such substates. The ability to determine quaternary structure substates of GPCRs provides exquisite means to elucidate functional relevance of GPCR oligomerization.
Routine measurement of serum procalcitonin allows antibiotics to be safely withheld in patients admitted to hospital with SARS-CoV-2 infection
Authors: Williams Emma J. , Mair Luke , de Silva Thushan I. , Green Dan J. , House Philip , Cawthron Kay , Gillies Christopher , Wigfull James , Parsons Helena , Partridge David G. 
Published: July 2020

ABSTRACTBackgroundIt can be a diagnostic challenge to identify COVID-19 patients without bacterial co-infection in whom antibiotics can be safely stopped. We sought to evaluate the validity of a guideline that recommends withholding antibiotics in patients with a low serum procalcitonin (PCT).MethodsWe retrospectively collected 28-day outcome data on patients admitted to Sheffield Teaching Hospitals NHS Foundation Trust, UK, between 5 March and 15 April 2020, with a positive SARS-CoV-2 polymerase chain reaction (PCR) and PCT within 48 hours of diagnosis. PCT was considered negative if ≤0.25ng/ml and positive if >0.25ng/ml. Primary outcomes included antibiotic consumption, mortality, intensive care admission and length of hospital stay.Results368 patients met the inclusion criteria; 218 (59%) had a negative PCT and 150 (41%) positive. At 48 hours post-diagnosis, 73 (33%) of those with a negative PCT were receiving antimicrobials compared to 126 (84%) with a positive PCT (p<0.001), with a corresponding reduction in antimicrobial usage over 28 days (median DDD of 3.0 vs 6.8 (p<0.001); median DOT 2 vs 5 days (p<0.001) between the negative and positive PCT groups.) In the negative PCT group, there were fewer deaths (62 (28%) vs. 54 (36%), (p=0.021)) and critical care admissions (19 (9%) vs. 28 (19%), (p=0.007)) than in the positive PCT group. Median length of hospital stay was 8.7 and 9 days in the negative and positive PCT groups respectively.ConclusionsProcalcitonin is a valuable tool in the assessment of patients with SARS-CoV-2 infection, safely reducing the potential burden of unnecessary antibiotic usage.
Improved contiguity of the threespine stickleback genome using long-read sequencing
Authors: Nath Shivangi , Shaw Daniel E. , White Michael A. 
Published: July 2020

AbstractWhile the cost and time for assembling a genome have drastically reduced, it still remains a challenge to assemble a highly contiguous genome. These challenges are rapidly being overcome by the integration of long-read sequencing technologies. Here, we use long sequencing reads to improve the contiguity of the threespine stickleback fish(Gasterosteus aculeatus)genome, a prominent genetic model species. Using Pacific Biosciences sequencing, we were able to fill over 76% of the gaps in the genome, improving contiguity over five-fold. Our approach was highly accurate, validated by 10X Genomics long-distance linked-reads. In addition to closing a majority of gaps, we were able to assemble segments of telomeres and centromeres throughout the genome. This highlights the power of using long sequencing reads to assemble highly repetitive and difficult to assemble regions of genomes. This latest genome build has been released through a newly designed community genome browser that aims to consolidate the growing number of genomics datasets available for the threespine stickleback fish.
The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases
Authors: Mäkinen Janne J. , Shin Yeonoh , Vieras Eeva , Virta Pasi , Metsä-Ketelä Mikko , Murakami Katsuhiko S. , Belogurov Georgiy A. 
Published: July 2020

AbstractRNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2’dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2’ OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2’dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here we show that a conserved Arg residue uses a two-pronged strategy to select against 2’dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2’OH group to promote NTP binding, but selectively inhibits incorporation of 2’dNTPs by interacting with their 3’OH group to favor the catalytically-inert 2’-endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs.
How do biases in sex ratio and disease characteristics affect the spread of sexually transmitted infections?
Authors: Halimubieke Naerhulan , Pirrie Alistair , Székely Tamás , Ashby Ben 
Published: July 2020

AbstractThe epidemiology of sexually transmitted infections (STIs) is inherently linked to host mating dynamics. Studies across many taxa show that adult sex ratio, a major determinant of host mating dynamics, is often skewed - sometimes strongly - toward males or females. However, few predictions exist for the effects of skewed sex ratio on STI epidemiology, and none when coupled with sex biased disease characteristics. Here we use mathematical modelling to examine how interactions between sex ratio and disease characteristics affect STI prevalence in males and females. Notably, we find that while overall disease prevalence peaks at equal sex ratios, prevalence per sex peaks at skewed sex ratios. Furthermore, disease characteristics, sex-biased or not, drive predictable differences in male and female STI prevalence as sex ratio varies, with higher transmission and lower virulence generally increasing differences between the sexes for a given sex ratio. These findings may be due to a balance between increased per-capita mating in the less common sex, and a reduction in mating rate - hence disease prevalence - at the population level. Our work reveals new insights into how STI prevalence in males and females depends on a complex interaction between host population sex ratio and disease characteristics.
Analysis of Virus-Host Interactomes through a network-centric approach
Authors: Tradigo Giuseppe , Veltri Pierangelo , Guzzi Pietro Hiram 
Published: July 2020

AbstractViruses are small microorganisms that invade living cells and use them to replicate themselves. Viruses cause many common human infections (such as cold flu) as well as many lethal diseases. Therefore the comprehensive knowledge of mechanisms used by viruses to infect living cells, also known as host-pathogen interactions, is crucial. Mechanisms of infections of viruses are mediated by Protein-protein interactions (PPIs). PPIs are often modelled using graphs, thus the use of such a model may also explain mechanisms of infection of viruses. In this work, we propose a methodology to model and analyse host-pathogen interactions and a supporting tool able to analyse such data. We also analyse host-pathogen interactions of some common viruses demonstrating common mechanism and differences.
Fourier spectral density of the coronavirus genome
Authors: Tan H.S. 
Published: July 2020

AbstractWe present an analysis of the coronavirus RNA genome via a study of its Fourier spectral density based on a binary representation of the nucleotide sequence. We find that at low frequencies, the power spectrum presents a small and distinct departure from the behavior expected from an uncorrelated sequence. We provide a couple of simple models to characterize such deviations. Away from a small low-frequency domain, the spectrum presents largely stochastic fluctuations about fixed values which vary inversely with the genome size generally. It exhibits no other peaks apart from those associated with triplet codon usage. We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density.
Automated design of synthetic microbial communities
Authors: Karkaria Behzad D. , Fedorec Alex J. H. , Barnes Chris P. 
Published: July 2020

AbstractIn naturally occurring microbial systems, species rarely exist in isolation. There is strong ecological evidence for a positive relationship between species diversity and the functional output of communities. The pervasiveness of these communities in nature highlights that there may be advantages for engineered strains to exist in cocultures as well. Building synthetic microbial communities allows us to create distributed systems that mitigates issues often found in engineering a monoculture, especially when functional complexity is increasing. Here, we demonstrate a methodology for designing robust synthetic communities that use quorum sensing to control amensal bacteriocin interactions in a chemostat environment. We explore model spaces for two and three strain systems, using Bayesian methods to perform model selection, and identify the most robust candidates for producing stable steady state communities. Our findings highlight important interaction motifs that provide stability, and identify requirements for selecting genetic parts and tuning the community composition.
Inhibition of CMP-sialic acid transport by endogenous 5-methyl CMP
Authors: Ahuja Shivani , Cahill James , Hartfield Kimberly , Whorton Matthew R. 
Published: July 2020

AbstractNucleotide-sugar transporters (NSTs) transport nucleotide-sugar conjugates into the Golgi lumen where they are then used in the synthesis of glycans. We previously reported crystal structures of a mammalian NST, the CMP-sialic acid transporter (CST) (Ahuja and Whorton 2019). These structures elucidated many aspects of substrate recognition, selectivity, and transport; however, one fundamental unaddressed question is how the transport activity of NSTs might be physiologically regulated as a means to produce the vast diversity of observed glycan structures. Here, we describe the discovery that an endogenous methylated form of cytidine monophosphate (m5CMP) binds and inhibits CST. The presence of m5CMP in cells results from the degradation of RNA that has had its cytosine bases post-transcriptionally methylated through epigenetic processes. Therefore, this work not only demonstrates that m5CMP represents a novel physiological regulator of CST, but it also establishes a link between epigenetic control of gene expression and regulation of glycosylation.
MappingDrosophilainsulin receptor structure to the regulation of aging through analysis of amino acid substitutions
Authors: Yamamoto Rochele , Palmer Michael , Koski Helen , Curtis-Joseph Noelle , Tatar Marc 
Published: July 2020

ABSTRACTGenetic manipulations of theDrosophilainsulin/IGF signaling system slow aging, but it remains unknown how the insulin/IGF receptor acts to modulate lifespan or differentiate this control from that of growth, reproduction and metabolism. With homologous recombination we produced an allelic series of single amino acid substitutions in the fly insulin receptor (InR). Based on emerging biochemical and structural data, we map amino acid substitutions to receptor function to longevity and fecundity. We proposeInRmutants generate bias in the process of asymmetric transphosphorylation when the receptor is activated. This induces specific kinase subdomains that modulate lifespan by additive processes, one involving survival costs of reproduction and the other involving reproduction-independent systems of longevity assurance. We identify a mutant in the kinase insert domain that robustly extends lifespan without affecting growth or reproduction, suggesting this element controls aging through unique mechanisms of longevity assurance.
TADA – a Machine Learning Tool for Functional Annotation based Prioritisation of Putative Pathogenic CNVs
Authors: Hertzberg J. , Mundlos S. , Vingron M. , Gallone G. 
Published: July 2020

AbstractThe computational prediction of disease-associated genetic variation is of fundamental importance for the genomics, genetics and clinical research communities. Whereas the mechanisms and disease impact underlying coding single nucleotide polymorphisms (SNPs) and small Insertions/Deletions (InDels) have been the focus of intense study, little is known about the corresponding impact of structural variants (SVs), which are challenging to detect, phase and interpret. Few methods have been developed to prioritise larger chromosomal alterations such as Copy Number Variants (CNVs) based on their pathogenicity. We address this issue with TADA, a method to prioritise pathogenic CNVs through manual filtering and automated classification, based on an extensive catalogue of functional annotation supported by rigorous enrichment analysis. We demonstrate that our machine-learning classifiers for deletions and duplications are able to accurately predict pathogenic CNVs (AUC: 0.8042 and 0.7869, respectively) and produce a well-calibrated pathogenicity score. The combination of enrichment analysis and classifications suggests that prioritisation of pathogenic CNVs based on functional annotation is a promising approach to support clinical diagnostic and to further the understanding of mechanisms that control the disease impact of larger genomic alterations.
Dynamics of bacterial cell division: Z ring condensation is essential for cytokinesis
Authors: Squyres Georgia R. , Holmes Matthew J. , Barger Sarah R. , Pennycook Betheney R. , Ryan Joel , Yan Victoria T. , Garner Ethan C. 
Published: July 2020

AbstractHow proteins in the bacterial cell division complex (the divisome) coordinate to divide bacteria remains unknown. To explore how these proteins collectively function, we conducted a complete dynamic characterization of the proteins involved, and then examined the function of FtsZ binding proteins (ZBPs) and their role in cytokinesis. We find that the divisome consists of two dynamically distinct subcomplexes: stationary ZBPs that transiently bind to treadmilling FtsZ filaments, and a directionally-moving complex that includes cell wall synthases. FtsZ filaments treadmill at steady state and the ZBPs have no effect on filament dynamics. Rather, ZBPs bundle FtsZ filaments, condensing them into Z rings. Z ring condensation increases the recruitment of cell wall synthesis enzymes to the division site, and this condensation is necessary for cytokinesis.
Correlating cell function and morphology by performing fluorescent immunocytochemical staining on the light-microscope stage
Authors: Kawano Hiroyuki , Kakazu Yasuhiro , Iwabuchi Sadahiro , Harata N. Charles 
Published: July 2020

ABSTRACTBackgroundCorrelation of fluorescence signals from functional changes in live cells with those from immunocytochemical indicators of their morphology following chemical fixation can be highly informative with regard to function-structure relationship. Such analyses can be technically challenging because they need consistently aligning the images between imaging sessions. Existing solutions include introducing artificial spatial landmarks and modifying the microscopes. However, these methods can require extensive changes to the experimental systems.New methodHere we introduce a simple approach for aligning images. It is based on two procedures: performing immunocytochemistry while a specimen stays on a microscope stage (on-stage), and aligning images using biological structures as landmarks after they are observed with transmitted-light optics in combination with fluorescence-filter sets.ResultsWe imaged a transient functional signal from a fluorescent Ca2+indicator, and mapped it to neurites based on immunocytochemical staining of a structural marker. In the same preparation, we could identify presynaptically silent synapses, based on a lack of labeling with an indicator for synaptic vesicle recycling and on positive immunocytochemical staining for a structural marker of nerve terminals. On-stage immunocytochemistry minimized lateral translations and eliminated rotations, and transmitted-light images of neurites were sufficiently clear to enable spatial registration, effective at a single-pixel level.Comparison with existing methodsThis method aligned images with minimal change or investment in the experimental systems.ConclusionsThis method facilitates information retrieval across multiple imaging sessions, even when functional signals are transient or local, and when fluorescent signals in multiple imaging sessions do not match spatially.
Do the Moroccan SARS-CoV-2 genetic diversity hamper the use of the developed universal vaccines in Morocco?
Authors: Laamarti Meriem , Essabbar Abdelomunim , Alouane Tarek , Kartti Souad , Boumajdi Nasma , Bendani Houda , Laamarti Rokia , Allam Loubna , Ouadghiri Mouna , Chemao-Elfihri M.W. , Ghrifi Fatima , Smyej Imane , Rahoui Jalila , Benrahma Houda , Diawara Idrissa , Aanniz Tarik , El Hafidi Naima , El Jaoudi Rachid , Nejjari Chakib , Amzazi Saaid , Mentag Rachid , Belyamani Lahcen , Ibrahimi Azeddine 
Published: July 2020

AbstractThe SARS-CoV-2 identified as coronavirus species associated with severe acute respiratory syndrome. At the time of writing, the genetic diversity of Moroccan strains of SARS-CoV-2 is poorly documented. The present study aims to analyze and identify the genetic variants of fortyeight Moroccan strains of SARS-CoV-2 collected from mid-March to the end of May and the prediction of their possible sources. Our results revealed 108 mutations in Moroccan SARS-CoV-2, 50% were non-synonymous were present in seven genes (S, M, N, E, ORF1ab, ORF3a, and ORF8) with variable frequencies. Remarkably, eight non-synonymous mutations were predicted to have a deleterious effect for (ORF1ab, ORF3a, and the N protein. The analysis of the haplotype network of Moroccan strains suggests different sources of SARS-CoV-2 infection in Morocco. Likewise, the phylogenetic analysis revealed that these Moroccan strains were closely related to those belonging to the five continents, indicating no specific strain dominating in Morocco. These findings have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information, and clinical characteristics of SARS-CoV-2 patients in Morocco and could indicate that the developed vaccines are likely to be effective against Moroccan strains.
Step-wise increases inFT1expression regulate seasonal progression of flowering in wheat (Triticum aestivumL.)
Authors: Gauley Adam , Boden Scott A. 
Published: July 2020

ABSTRACTFlowering is regulated by genes that respond to changing daylengths and temperature, which have been well-studied using controlled conditions; however, the molecular processes underpinning flowering in nature remain poorly understood. Here, we investigate the genetic pathways that coordinate flowering and inflorescence development of wheat as daylengths extend naturally in the field, using lines that contain variant alleles for the key photoperiod gene,Photoperiod-1(Ppd-1). We found flowering involves a step-wise increase in the expression ofFLOWERING LOCUS T1(FT1), which initiates under day-neutral conditions of early spring. The incremental rise inFT1expression is overridden in plants that contain a photoperiod-insensitive allele ofPpd-1, which hastens the completion of spikelet development and accelerates flowering time. The accelerated inflorescence development of photoperiod-insensitive lines is promoted by advanced seasonal expression of floral meristem identity genes. The completion of spikelet formation is promoted byFLOWERING LOCUS T2, which regulates spikelet number and is activated byPpd-1. In wheat, flowering under natural photoperiods is regulated by step-wise increases in the expression ofFT1, which responds dynamically to extending daylengths to promote early inflorescence development. This research provides a strong foundation to improve yield potential by fine-tuning the photoperiod-dependent control of inflorescence development.