bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects
Authors: Nguyen Hanh T. , Zhang Shijian , Wang Qian , Anang Saumya , Wang Jia , Ding Haitao , Kappes John C. , Sodroski Joseph 
Published: October 2020

ABSTRACTSARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects. We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced the ability to form lethal syncytia. Notably, the D614G change found in globally predominant SARS-CoV-2 strains restored infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, two unique features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.IMPORTANCEThe development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, which contributes to the destruction of the virus-infected cell.
A novel method for measuring phenotypic colistin resistance inEscherichia colipopulations from chicken flocks
Authors: Nguyen Nhung Thi , Yen Nguyen Thi Phuong , Van Ky Thien Nguyen , Van Cuong Nguyen , Kiet Bach Tuan , Campbell James , Thwaites Guy , Baker Stephen , Geskus Ronald B. , Carrique-Mas Juan 
Published: October 2020

ABSTRACTColistin is extensively used in animal production in many low- and middle-income countries. There is a need to develop methodologies to benchmark and monitor changes in resistance in commensal bacterial populations in farms. We aimed to evaluate the performance of a broth microdilution method based on culturing a pooledEscherichia colisuspension (30-50 organisms) from each sample. In order to confirm the biological basis and sensitivity of the method, we prepared 16 standard suspensions containing variable ratios of colistin-susceptible andmcr-1 encoded colistin-resistantE. coliwhich were grown in 2mg/L colistin. The optical density (OD600nm) readings over time were used to generate a growth curve, and were adjusted to the values obtained in the absence of colistin. The median limit of detection of the method was 1 colistin-resistant in 104susceptible colonies [1st- 3rdquartile, 1:102– 1:105]. We applied this method to 108 pooled faecal samples from 36 chicken flocks in the Mekong Delta (Vietnam) over the production cycle. The correlation between this method and the prevalence of colistin resistance in individual colonies harvested from field samples, determined by the Minimum Inhibitory Concentration (MIC), was established. The overall prevalence of colistin resistance at sample and isolate level was 38.9% and 19.4%, respectively. Increased colistin resistance was associated with recent (2 weeks) use of colistin and other, non-colistin antimicrobials (OR=3.67 and OR=1.84, respectively). Our method is a sensitive and affordable approach to monitor changes in colistin resistance in pooledE. colipopulations from faecal samples over time.IMPORTANCEColistin (polymyxin E) is an antimicrobial with poor solubility properties, and therefore broth microdilution is the only appropriate method for testing colistin resistance. However, estimating colistin resistance in commensal mixedEscherichia colipopulations is laborious since it requires individual colony isolation, identification and susceptibility testing. We developed a growth-based microdilution method suitable for pooled faecal samples. We validated the method by comparing it with results from individual MIC testing of 909E. coliisolates. We used the method to investigate phenotypic colistin resistance in 108 pooled faecal samples from 36 healthy chicken flocks, each sampled three times over the production cycle. A higher level of resistance was seen in flocks recently supplemented with colistin in drinking water, although the observed generated resistance was short-lived. Our method is affordable, and may potentially be integrated into surveillance systems aiming at estimating the prevalence of resistance at colony level in flocks/herds. Furthermore, it may also be adapted to other complex biological systems, such as farms and abattoirs.
Dynamics of sex chromosome evolution in a rapid radiation of cichlid fishes
Authors: Taher Athimed El , Ronco Fabrizia , Matschiner Michael , Salzburger Walter , Böhne Astrid 
Published: October 2020

AbstractSex is a fundamental trait that is determined, depending on the species, by different environmental and/or genetic factors, including various types of sex chromosomes. While the functioning and emergence of sex chromosomes have been explored in species scattered across the eukaryotic tree of life, little is known about tempo and mode of sex chromosome evolution in closely related species. Here, we examine the dynamics of sex chromosome evolution in an archetypical example of adaptive radiation, the cichlid fishes of African Lake Tanganyika. Through inspection of male and female genomes from 244 cichlid taxa and the analysis of transcriptomes from 66 taxa, we identify signatures of sex chromosomes in 79 taxa, involving 12 different linkage groups. We estimate that Tanganyikan cichlids have the highest rates of sex chromosome turnover and heterogamety transitions known to date. We further show that the recruitment of chromosomes as sex chromosomes is not at random and that some chromosomes have convergently emerged as sex chromosomes in cichlids, which provides empirical support to the “limited options” hypothesis of sex chromosome evolution.
Morphological and phylogeographic evidence for budding speciation: an example in hominins
Authors: Parins-Fukuchi Caroline 
Published: October 2020

AbstractParametric phylogenetic approaches that attempt to delineate between distinct ‘modes’ of speciation (splitting cladogenesis, budding cladogenesis, and anagenesis) between fossil taxa have become increasingly popular among comparative biologists. But it is not yet well-understood how clearly morphological data from fossil taxa speak to detailed questions of speciation mode as compared to the lineage diversification models that serve as their basis. In addition, the congruence of inferences made using these approaches with geographic patterns has not been explored. Here, I extend a previously introduced maximum-likelihood approach for the examination of ancestor-descendant relationships to accommodate budding speciation and apply it to a dataset of fossil hominins. I place these results in a phylogeographic context to better understand spatial dynamics underlying the hypothesized speciation patterns. The spatial patterns implied by the phylogeny hint at the complex demographic processes underlying the spread and diversification of hominins throughout the Pleistocene. I also find that inferences of budding are driven primarily by stratigraphic, versus morphological, data and discuss the ramifications for interpretations of speciation process in hominins specifically and from phylogenetic data in general.
Single cell analyses reveal phosphate availability as critical factor for nutrition ofSalmonella entericawithin mammalian host cells
Authors: Röder Jennifer , Hensel Michael 
Published: October 2020

AbstractSalmonella entericaserovar Typhimurium (STM) is an invasive, facultative intracellular pathogen that resides in a specialized membrane-bound compartment termedSalmonella-containing vacuole (SCV). Essential for survival and proliferation in the SCV isSalmonellapathogenicity island II (SPI2) that encodes a type III secretion system (T3SS). The SPI2-T3SS and the effector translocation maintain SCV integrity and formation of specific tubular membrane compartments, calledSalmonella-induced filaments (SIFs). The SCV/SIF continuum allows STM to bypass nutritional restriction in the intracellular environment by acquiring nutrients from the host cell. Phosphate is one of the most abundant elements in living organisms and in STM, inorganic phosphate (Pi) homeostasis is mediated by the two-component regulatory system PhoBR, resulting in expression of the high affinity phosphate transporterpstSCAB-phoU.Using fluorescent protein reporters, we investigate Piavailability for STM at single cell level over time within the intracellular habitats of different host cells. We observed that thepstSCAB-phoUencoded phosphate uptake system is essential for intracellular replication of STM because there is a Piion concentration less 10 μM within the SCV. Additionally, the demand and consumption of Picorrelates with intracellular proliferation of STM and we identify a dependency of SPI2 activity and Pistarvation.
An evaluation of the interpretability and predictive performance of the BayesR model for genomic prediction
Authors: Mollandin Fanny , Rau Andrea , Croiseau Pascal 
Published: October 2020

ABSTRACTTechnological advances and decreasing costs have led to the rise of increasingly dense genotyping data, making feasible the identification of potential causal markers. Custom genotyping chips, which combine medium-density genotypes with a custom genotype panel, can capitalize on these candidates to potentially yield improved accuracy and interpretability in genomic prediction. A particularly promising model to this end is BayesR, which divides markers into four effect size classes. BayesR has been shown to yield accurate predictions and promise for quantitative trait loci (QTL) mapping in real data applications, but an extensive benchmarking in simulated data is currently lacking. Based on a set of real genotypes, we generated simulated data under a variety of genetic architectures, phenotype heritabilities, and we evaluated the impact of excluding or including causal markers among the genotypes. We define several statistical criteria for QTL mapping, including several based on sliding windows to account for linkage disequilibrium. We compare and contrast these statistics and their ability to accurately prioritize known causal markers. Overall, we confirm the strong predictive performance for BayesR in moderately to highly heritable traits, particularly for 50k custom data. In cases of low heritability or weak linkage disequilibrium with the causal marker in 50k genotypes, QTL mapping is a challenge, regardless of the criterion used. BayesR is a promising approach to simultaneously obtain accurate predictions and interpretable classifications of SNPs into effect size classes. We illustrated the performance of BayesR in a variety of simulation scenarios, and compared the advantages and limitations of each.
Morphometric and Molecular Discrimination of the sugarcane aphid,Melanaphis sacchari, (Zehntner, 1897) and the sorghum aphidMelanaphis sorghi(Theobald, 1904)
Authors: Nibouche Samuel , Costet Laurent , Medina Raul F. , Holt Jocelyn R. , Sadeyen Joëlle , Zoogones Anne-Sophie , Brown Paul , Blackman Roger L. 
Published: October 2020

AbstractMelanaphis sacchari(Zehntner, 1897) andMelanaphis sorghi(Theobald, 1904) are major worldwide crop pests causing direct feeding damage on sorghum and transmitting viruses to sugarcane. It is common in the scientific literature to consider these two species as synonyms, referred to as the ‘sugarcane aphid’, although no formal study has validated this synonymy. In this study, based on the comparison of samples collected from their whole distribution area, we use both morphometric and molecular data to better characterize the discrimination betweenM. sacchariandM. sorghi. An unsupervised multivariate analysis of morphometric data clearly confirmed the separation of the two species. The best discriminating characters separating these species were length of the antenna processus terminalis relative to length of hind tibia, siphunculus or cauda. However, those criteria sometimes do not allow an unambiguous identification. Bayesian clustering based on microsatellite data delimited two clusters, which corresponded to the morphological species separation. The DNA sequencing of three nuclear and three mitochondrial regions revealed slight divergence between species. In particular, the COI barcode region proved to be uninformative for species separation because one haplotype is shared by both species. In contrast, one SNP located on the nuclear EF1-α gene was diagnostic for species separation. Based on morphological and molecular evidence, the invasive genotype damaging to sorghum in the US, Mexico and the Caribbean since 2013 is found to beM. sorghi.
Characterization and variation of bacterial and fungal communities from the sapwood of Apulian olive varieties with different susceptibility toXylella fastidiosa
Authors: Hanani Arafat , Valentini Franco , Cavallo Giuseppe , Sanzani Simona Marianna , Santoro Franco , Minutillo Serena Anna , Gallo Marilita , El Moujabber Maroun , D’Onghia Anna Maria , Davino Salvatore Walter 
Published: October 2020

AbstractEndophytes are symptomless fungal and/or bacterial microorganisms found in almost all living plant species. The symbiotic association with their host plants by colonizing the internal tissues has endowed them as a valuable tool to suppress diseases, to stimulate growth, and to promote stress resistance. In this context, the identification of cultivable endophytes residing the sapwood of Apulian olives might be a promising control strategy for xylem colonizing pathogens asXylella fatidiosa. To date, olive’s sapwood cultivable endophytes are still under exploration; therefore, this work pursues a study of diversity and occurrence variation of cultivable endophytes in the sapwood of different olive varieties under the effect seasonality, geographical coordinates, andX. fastidiosainfection status. Briefly, our study confirms the stability of sapwood cultivable endophytic communities in the resistant olive variety, presents the seasonal and geographical fluctuation of olive’s sapwood endophytes, describes the diversity and occurrence frequency of fungal and bacterial genera, and finally retrieves some of sapwood-inhabiting fungal and bacterial isolates are known as biocontrol agents of plant pathogens. Thus, the potential role of these bacterial and fungal isolates in conferring olive tree protection againstX. fastidiosashould be further investigated.
Exposure to lysed bacteria can promote or inhibit growth of neighbouring live bacteria depending on local abiotic conditions
Authors: Smakman Fokko , Hall Alex R. 
Published: October 2020

AbstractMicrobial death is extremely common in nature, yet the ecological role of dead bacteria is unclear. Dead cells are assumed to provide nutrients to surrounding microbes, but may also affect them in other ways. We found adding lysate prepared from dead bacteria to cultures ofE. coliin nutrient-rich conditions suppressed their final population density. This is in stark contrast with the notion that the primary role of dead cells is nutritional, although we also observed this type of effect when we added dead bacteria to cultures that were not supplied with other nutrients. We only observed the growth-suppressive effect of dead bacteria after they had undergone significant lysis, suggesting a key role for cellular contents released during lysis. Transcriptomic analysis revealed changes in gene expression in response to dead cells in growing populations, particularly in genes involved in motility. This was supported by experiments with genetic knockouts and copy-number manipulation. Because lysis is commonplace in natural and clinical settings, the growth-suppressive effect of dead cells we describe here may be a widespread and previously unrecognized constraint on bacterial population growth.
ExoNet Database: Wearable Camera Images of Human Locomotion Environments
Authors: Laschowski Brock , McNally William , Wong Alexander , McPhee John 
Published: October 2020

AbstractAdvances in computer vision and artificial intelligence are allowing researchers to develop environment recognition systems for powered lower-limb exoskeletons and prostheses. However, small-scale and private training datasets have impeded the widespread development and dissemination of image classification algorithms for classifying human walking environments. To address these limitations, we developed ExoNet - the first open-source, large-scale hierarchical database of high-resolution wearable camera images of human locomotion environments. Unparalleled in scale and diversity, ExoNet contains over 5.6 million RGB images of different indoor and outdoor real-world walking environments, which were collected using a lightweight wearable camera system throughout the summer, fall, and winter seasons. Approximately 923,000 images in ExoNet were human-annotated using a 12-class hierarchical labelling architecture. Available publicly through IEEE DataPort, ExoNet offers an unprecedented communal platform to train, develop, and compare next-generation image classification algorithms for human locomotion environment recognition. Besides the control of powered lower-limb exoskeletons and prostheses, applications of ExoNet could extend to humanoids and autonomous legged robots.
Tracking pre-mRNA maturation across subcellular compartments identifies developmental gene regulation through intron retention and nuclear anchoring
Authors: Yeom Kyu-Hyeon , Pan Zhicheng , Lin Chia-Ho , Lim Hanyoung , Xiao Wen , Xing Yi , Black Douglas L. 
Published: October 2020

SUMMARYTo globally assess the distribution and processing of gene transcripts across subcellular compartments, we developed extensive RNA-seq datasets of both polyA+ and total RNA from chromatin, nucleoplasm and cytoplasm of mouse ESC, neuronal progenitors, and neurons. We identified protein-coding genes whose polyadenylated transcripts were more abundant in chromatin than cytoplasm. We defined introns exhibiting cotranscriptional splicing, complete intron retention in cytoplasmic RNA, and many introns retained in nucleoplasmic and chromatin RNA but absent from cytoplasmic RNA, including new introns controlled during neuronal development. In particular, we found that polyadenylatedGabbr1transcripts are expressed in mESC but remain sequestered on chromatin until neuronal differentiation when they are processed and released to the cytoplasm. This developmental regulation of splicing and chromatin association demonstrates that the abundance of polyadenylated RNA is not always an indicator of functional gene expression. Our datasets provide a rich resource for analyzing many other aspects of mRNA maturation.
Association Plots: Visualizing associations in high-dimensional correspondence analysis biplots
Authors: Gralinska Elzbieta , Vingron Martin 
Published: October 2020

SummaryIn molecular biology, just as in many other fields of science, data often come in the form of matrices or contingency tables with many measurements (rows) for a set of variables (columns). While projection methods like Principal Component Analysis or Correspondence Analysis can be applied for obtaining an overview of such data, in cases where the matrix is very large the associated loss of information upon projection into two or three dimensions may be dramatic. However, when the set of variables can be grouped into clusters, this opens up a new angle on the data. We focus on the question which measurements are associated to a cluster and distinguish it from other clusters. Correspondence Analysis employs a geometry geared towards answering this question. We exploit this feature in order to introduceAssociation Plotsfor visualizing cluster-specific measurements in complex data. Association Plots are two-dimensional, independent of the size of data matrix or cluster, and depict the measurements associated to a cluster of variables. We demonstrate our method first on a small data set and then on a genomic example comprising more than 10,000 conditions. We will show that Association Plots can clearly highlight those measurements which characterize a cluster of variables.
ATRX alteration contributes to tumor growth and immune escape in pleomorphic sarcomas
Authors: Darmusey Lucie , Pérot Gaëlle , Thébault Noémie , Guellec Sophie Le , Desplat Nelly , Gaston Laëtitia , Delespaul Lucile , Lesluyes Tom , Darbo Elodie , Gomez-Brouchet Anne , Richard Elodie , Baud Jessica , Leroy Laura , Coindre Jean-Michel , Blay Jean-Yves , Chibon Frédéric 
Published: October 2020

AbstractWhole genome and transcriptome sequencing of a cohort of 67 leiomyosarcomas revealedATRXto be one of the most frequently mutated genes in leiomyosarcomas afterTP53andRB1. While its function is well described in the alternative lengthening of telomeres mechanism, we wondered whether its alteration could have complementary effects on sarcoma oncogenesis.ATRXalteration is associated with the down-expression of genes linked to differentiation in leiomyosarcomas, and to immunity in an additional cohort of 60 poorly differentiated sarcomas.In vitroandin vivomodels showed thatATRXloss increases tumor growth rate and immune escape by decreasing the immunity load of active mast cells in sarcoma tumors. These data indicate that an alternative to unsuccessful targeting of the adaptive immune system in sarcoma could be to target the innate system. This might lead to a better outcome for sarcoma patients in terms ofATRXstatus.
One pathway, two cyclic pentapeptides: heterologous expression of BE-18257 A-C and pentaminomycins A-E fromStreptomyces cacaoiCA-170360
Authors: Román-Hurtado Fernando , Sánchez-Hidalgo Marina , Martín Jesús , Ortiz-López Francisco Javier , Carretero-Molina Daniel , Reyes Fernando , Genilloud Olga 
Published: October 2020

1.AbstractThe strainStreptomyces cacaoiCA-170360 produces the cyclic pentapeptides pentaminomycins A-E and BE-18257 A-C, two families of cyclopeptides synthesized by two nonribosomal peptide synthetases encoded in tandem within the same biosynthetic gene cluster. In this work, we have cloned and confirmed the heterologous expression of this biosynthetic gene cluster, demonstrating that each of the nonribosomal peptide synthetases present in the cluster is involved in the biosynthesis of each group of cyclopeptides. In addition, we discuss the involvement of a stand-alone enzyme belonging to the Penicillin Binding Protein family in the release and macrocyclization of the peptides.