bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic analysis of putative SARS-CoV-2 entry and processing genes in cardiovascular tissues identifies a positive correlation of BSG with age in endothelial cells
Authors: Ahmetaj-Shala Blerina , Vaja Ricky , Atanur Santosh S , George Peter M. , Kirkby Nicholas S. , Mitchell Jane A. 
Published: June 2020

AbstractCOVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread throughout the world with unprecedented global healthcare and socio-economic consequences. There is now an established secondary syndrome of COVID-19 characterised by thrombosis, vascular dysfunction and hypertension, seen in those most severely affected. Advancing age in adults is the single most significant risk factor for hospitalisation and death with COVID-19. In light of the cardiovascular/thrombotic sequalae associated with severe COVID-19 disease and the overwhelming risk that increased age carries, in this study, our aim was to obtain mechanistic insight by interrogating gene expression profiles in cardiovascular tissues and cells. Our focus was on the two putative receptors for SARS-CoV-2,ACE2andBSGalong with a selected range of genes thought to be involved in virus binding/processing. In this study we have made four important observations: (i)Cardiovascular tissues and/or endothelial cells express the required genes for SARS-CoV-2 infection, (ii) SASR-CoV-2 receptor pathways,ACE2/TMPRSS2andBSG/PPIB(A) polarise to lung/epithelium and vessel/endothelium respectively, (iii) expression of SARS-CoV-2 host genes are, on the whole, relatively stable with age and (iv) notable exceptions wereACE2which decreases with age in some tissues andBSGwhich increases with age in endothelial cells. Our data support the idea that that BSG is the dominate pathway utilised by SARS-CoV-2 in endothelial cells and are the first to demonstrate a positive correlation with age. We suggest BSG expression in the vasculature is a critical driver which explains the heightened risk of severe disease and death observed in those >40 years of age. Since BSG is utilised by other pathogens our findings have implications beyond the current pandemic. Finally, because BSG is functions in a range of cardiovascular diseases and fibrosis, our observations may have relevance to our understanding of the diseases associated with aging.
Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco
Authors: Badaoui Bouabid , Sadki Khalid , Talbi Chouhra , Driss Salah , Tazi Lina 
Published: June 2020

AbstractCOVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world.The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.
Identification of a novel LysR-type transcriptional regulator inStaphylococcus aureusthat is crucial for secondary tissue colonization during metastatic bloodstream infection
Authors: Groma Michaela , Horst Sarah , Das Sudip , Huettel Bruno , Klepsch Maximilian , Rudel Thomas , Medina Eva , Fraunholz Martin 
Published: June 2020

AbstractStaphylococcus aureusis a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection into secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used aS. aureustransposon mutant library coupled to transposon insertion sequencing (Tn-Seq) to identify genes that are critical for efficient bacterial colonization of secondary organs in a murine model of metastatic bloodstream infection. Our transposon screen identified a LysR-type transcriptional regulator (LTTR), which was required for efficient colonization of secondary organs such as the kidneys in infected mice. The critical role of LTTR in secondary organ colonization was confirmed using an isogenic mutant deficient in the expression of LTTR. To identify the set of genes controlled by LTTR, we used aS. aureusstrain carrying the LTTR gene in an inducible expression plasmid. Gene expression analysis upon induction of LTTR showed increased transcription of genes involved in branched chain amino-acid biosynthesis, a methionine sulfoxide reductase and a copper transporter as wells as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enable a rapid adaptation ofS. aureusto the changing host microenvironment.
Structure of core fungal endobiome inUlmus minor: patterns within the tree and across genotypes differing in tolerance to Dutch elm disease
Authors: Macaya-Sanz David , Witzell Johanna , Collada Carmen , Gil Luis , Martin Juan Antonio 
Published: June 2020

AbstractPlants harbour a diverse fungal community with complex symbiotic interactions and significant roles in host physiology. However, the cues that steer the composition and structure of this community are poorly understood. Trees are useful models for assessing these factors because their large size and long lifespan give these ecosystems time and space to evolve and mature. Investigation of well-characterised pathosystems such as Dutch elm disease (DED) can reveal links between endomycobiome and pathogens. We examined the endophytic mycobiome across the aerial part of a landmark elm tree to identify structural patterns within plant hosts, highlighting not only commonalities but also the effect of local infections in some branches of the crown. We used a common garden trial of trees with varying levels of genotypic susceptibility to DED to identify associations between susceptibility and endomycobiome. Three families of yeasts were linked to higher DED tolerance: Buckleyzymaceae, Herpotrichiellaceae and Tremellaceae. Surveying a natural population with a gradient of vitality, we found some taxa enriched in declining trees. By combining all surveys and adding a further study in a distant natural population, we found evidence of aU. minorcore mycobiome, pervasive within the tree and ubiquitous across locations, genotypes and health status.
Projecting single-cell transcriptomics data onto a reference T cell atlas to interpret immune responses
Authors: Andreatta Massimo , Corria-Osorio Jesus , Müller Sören , Cubas Rafael , Coukos George , Carmona Santiago J. 
Published: June 2020

SummarySingle-cell RNA-sequencing (scRNA-seq) has emerged as a revolutionary technology for characterizing the heterogeneity of cell populations. However, robust reference atlases that can be used to systematically interpret cellular states across studies and diseases are currently lacking. Here, we generated the first cross-study T cell atlases for cancer and viral infection and developed a novel algorithm, ProjecTILs, that enables the projection of new scRNA-seq data onto these reference atlases. ProjecTILs accurately predicted the effects of multiple perturbations, including the ablation of immunoregulatory targets controlling T cell differentiation, such asTox,Ptpn2,miR-155andRegnase-1, and suggested novel gene programs that were altered in these cells. Moving beyond mouse models, we used ProjecTILs to conduct a meta-analysis of human tumor-infiltrating T lymphocytes (TILs), revealing a remarkable conservation of TIL subtypes between human and mouse and across cancer types. Clonotype analysis supported a model in which rare human tumor-specific effector-memory (EM)-like CD8 TILs that resemble blood-circulating EM cells, differentiate into proliferative terminal exhausted/dysfunctional effector TILs through a progenitor subtype that upregulates the exhaustion master regulatorTOX. Our novel computational method allows exploring the effect of human and murine T cell perturbations (e.g.as the result of therapy or genetic engineering) in terms of reference cellular states, altered genetic programs and clonotype structure, revealing mechanisms of action behind immunotherapies and opening opportunities for their improvement.
Nanoparticle Tracking Analysis: A powerful tool for characterizing magnetosome preparations
Authors: Fernández-Castané Alfred , Li Hong , Joseph Stephan , Ebeler Moritz , Franzreb Matthias , Bracewell Daniel G. , Overton Tim W. , Thomas Owen R.T. 
Published: June 2020

AbstractNanoparticle Tracking Analysis (NTA) has been employed to measure the particle concentration and size distribution of magnetosomes extracted and purified fromMagnetospirillum gryphiswaldenseMSR-1, and then exposed to probe ultrasonication for various times, or 1% (w/v) sodium dodecyl sulphate (SDS) for 1 h. Particle concentration increased 3.7-fold over the first 15 min of ultrasonication (from 2 × 108to >7.3 × 108particles mL−1), but fell steeply to ~3.6 × 108particles mL−1after 20 min. NTA of untreated magnetosome preparation confirmed a wide particle distribution dominated by larger species (D[1,0] = 312 nm; Dn50= 261 nm; mode = 243 nm) with no particles in the size range of isolated single magnetosomes. After 5 min of ultrasonication the whole particle size distribution shifted to smaller size (D[1,0] = 133 nm; Dn50= 99 nm; mode = 36 nm, corresponding to individual magnetosomes), but longer treatment times (15 and 20 min) reversed the previous transition; all characteristic numbers of the particle size distributions increased and very few small particles were detected. Side-by-side comparison of NTA and TEM sizing data revealed remarkable similarity at low ultrasonication times, with both showing single magnetosomes accounted for ~30% population after 5 min. Exposure of magnetosomes to SDS resulted in a ~3-fold increase in particle concentration to 5.8 × 108particles mL−1, narrowing of the size distribution and gross elimination of particles below 60 nm. We conclude that NTA is a rapid cost-effective technique for measuring particle number, size distribution and aggregation state of magnetosomes in solution, but requires further work to improve its resolving power.
Respiratory Syncytial Virus in Infants and Children with Prader-Willi syndrome
Authors: Miller JL , Thornton E 
Published: June 2020

ABSTRACTBACKGROUNDPrader-Willi syndrome (PWS) is a complex disorder affecting approximately 1/15,000-1/30,000 people. Infants with PWS are at risk for serious complications with Respiratory Syncytial Virus (RSV) due to low muscle tone and a weakened pulmonary system.OBJECTIVESUnderstanding RSV incidence, hospitalization rates, lingering effects, and morbidity in children with PWS may help with planning health care, insurance and vaccine recommendations in children with PWS.METHODSLinks to volunteer surveys were provided via direct email and social media to families throughout the United States with children having PWS. The contact distribution lists were provided by PWSA(USA) and the Foundation for Prader-Willi Research.RESULTSA total of 220 surveys were completed by the parents/caregivers of children with PWS. Of those respondents, 60 (27.27%) had contracted the RSV virus during early childhood. Of those with RSV, 44 children required hospitalization, with 16 reporting multiple hospitalizations, some for several weeks. Of those with the virus, 22 required PICU admission, 10 required intubation, 20 needed CPAP, and 46 children needed supplemental oxygen during the infection. Of those who had contracted RSV, 42% were over age 1 year at the time of infection, and 17 children developed chronic lung issues after the RSV infection. The case lethality was 1.37%.Only 38% had received the RSV Synagis shot, and 19% received more than one season of the vaccination. Prematurity prevalence was only 28%, but 99% reported that their child had significant hypotonia.Approximately 30% of parents sited lack of insurance authorization or failure of the physician to recommend the treatment.CONCLUSIONSThe risk of contracting RSV for young children with PWS is high. The implications of contracting RSV include death or lung damage, along with high medical expenditures, which could be ameliorated with routine administration of the Synagis vaccine.
Differential Gene Expression Analysis and Cytological Evidence Reveal a Sexual Stage of an Amoeba with Multiparental Cellular and Nuclear Fusion
Authors: Tekle Yonas I. , Wang Fang , Heidari Alireza , Stewart Alanna Johnson 
Published: June 2020

AbstractSex is a hallmark of eukaryotes but its evolution in microbial eukaryotes is poorly elucidated. Recent genomic studies revealed microbial eukaryotes possess genetic toolkit necessary for sexual reproduction. However, the mechanism of sexual development in a majority of microbial eukaryotes including amoebozoans is poorly characterized. The major hurdle in studying sex in microbial eukaryotes is lack of observational evidence, primarily due to its cryptic nature. In this study, we used a tractable fusing amoeba,Cochliopodium,to investigate sexual development using stage specific Differential Gene Expression (DGE) and cytological analyses. Both DGE and cytological results showed that most of the meiosis and sex-related genes are upregulated inCochliopodiumundergoing fusion in laboratory culture. Relative gene ontology (GO) category representations in unfused (single) and fused cells revealed functional skew of the fused transcriptome toward DNA metabolism, nucleus and ligases that are suggestive of a commitment to sexual development. While single cells GO categories were dominated by metabolic pathways and other processes indicative of vegetative phase. Our study provides strong evidence that the fused cells represent a sexual stage inCochliopodium.Our findings have further implications in understanding the evolution and mechanism of inheritance involving multiparents in other eukaryotes with similar reproductive strategy.
Allosteric inhibition of adenylyl cyclase type 5 by G-protein: a molecular dynamics study
Authors: Frezza Elisa , Amans Tina-Méryl , Martin Juliette 
Published: June 2020

AbstractAdenylyl cyclases (ACs) have a crucial role in many signal transduction pathways, in particular in the intricate control of cyclic AMP (cAMP) generation from adenosine triphosphate (ATP). Using homology models developed from existing structural data and docking experiments, we have carried out all-atom, microsecond-scale molecular dynamics simulations on the AC5 isoform of adenylyl cyclase bound to the inhibitory G-protein subunit Gαi in the presence and in the absence of ATP. The results show that Gαi have significant effects on the structure and flexibility of adenylyl cyclase, as observed earlier for the binding of ATP and Gsα. New data on Gαi bound to the C1 domain of AC5 help to explain how Gαi inhibits enzyme activity and to get insight on its regulation. Simulations also suggest a crucial role of ATP in the regulation of stimulation and inhibition of AC5.Author summaryThe neurons that compose the human brain are able to respond to multiple inputs from other neurons. The chemical “integration” of these inputs then decides whether a given neuron passes on a signal or not. External chemical messages act on neurons via proteins in their membranes that trigger cascades of reactions within the cell. One key molecule in these signaling cascades is cyclic adenosine monophosphate (cAMP) that is chemically synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase (AC). We are investigating the mechanisms that control how much cAMP is produced as a function of the signals received by the neuron. In particular, we have studied the inhibition effect of a key protein, termed Gαi, on AC, and we compare it with the stimulator effect of another key protein termed Gsα. Using microsecond molecular simulations, we have been able to show how binding Gαi to AC changes its structure and its dynamics so that its enzymatic activity is quenched and that ATP seems to have a crucial role in the regulation of stimulation and inhibition of AC5.
Dynein collective behavior in mitotic nuclear positioning ofSaccharomyces cerevisiae
Authors: Jain Kunalika , Khetan Neha , Palani Saravanan , Athale Chaitanya A. 
Published: June 2020

1AbstractPositioning the nucleus at the bud-neck prior duringSaccharomyces cerevisiaemitosis during anaphase involves pulling forces of cytoplasmic dynein localized in the daughter cell. While genetic analysis has revealed a complex network positioning the nucleus, quantification of the forces acting on the nucleus and dyneins numbers driving the process has remained difficult. In order to better understand the role of motor-microtubule mechanics during nuclear positioning and the role of dynein, we have used a computational model of nuclear mobility inS. cerevisiaeand reconciled it to the mobility of labelled spindle pole bodies (SPBs) measured by quantifying fluorescence microscopy time-series. We model the apparent random-walk mobility of SPBs by combining diffusion of the nucleus and active pushing of MTs at the cell membrane. By minimizing the deviation between tracks of fluorescently tagged SPBs and simulations, we estimate the effective cytoplasmic viscosity to be 0.5 Pa s. The directed transport of nuclei during the budding process is similarly quantified by tracking the daughter SPB (SPB-D) in experiment. Using force-balance, we find 2 to 8 motors are required to pull the nucleus to the bud-neck. Simulations of the cytoplasmic MT (cMT) ‘search and capture’ by dynein suggest single motor binding is followed by a rapid saturation of number of bound motors. The short time and length of MT interactions with the cortex and minimal collective dynein force required, predict a functional role for dynein clustering in nuclear positioning.
Effects of gonadectomy and androgen on neuronal plasticity in motivation and reward related brain regions in the male rat
Authors: Huijgens Patty T. , Snoeren Eelke M.S. , Meisel Robert L. , Mermelstein Paul G. 
Published: June 2020

AbstractGonadal hormones affect neuronal morphology to ultimately regulate behavior. Here, we investigated the effect of both castration and androgen replacement on spine plasticity in the nucleus accumbens shell and core (NAcSh and NAcC), caudate putamen (CPu), medial amygdala (MeA), and medial preoptic nucleus (MPN). Intact and castrated (GDX) male rats were treated with dihydrotestosterone (DHT, 1.5mg) or vehicle (oil) in 3 experimental groups: intact-oil, GDX-oil and GDX-DHT. Spine density and morphology, measured 24 hours after injection, were determined through 3D reconstruction of DiI-labeled dendritic segments. GDX decreased spine density in the MPN, which was rescued by DHT treatment. MeA spine density increased in GDX-DHT animals compared to intact-oil animals. In the NAcSh, DHT decreased spine density, and also rapidly increased the number of pCREB+ cell bodies. These findings indicate that androgen signaling plays a role in the regulation of spine plasticity within neurocircuits involved in motivated behaviors.
PlexinA4-Semaphorin3A mediated crosstalk between main cortical interneuron classes is required for superficial interneurons lamination
Authors: Limoni Greta , Niquille Mathieu , Murthy Sahana , Jabaudon Denis , Dayer Alexandre 
Published: June 2020

SummaryIn the mammalian cerebral cortex, the developmental events governing the allocation of different classes of inhibitory interneurons (INs) into distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 (PLXNA4) is upregulated in serotonin receptor 3a-expressing (HTR3A+) cortical INs (hINs) as they invade the cortical plate and that it regulates their laminar allocation to superficial cortical layers. We find that the PLXNA4 ligand Semaphorin3A (SEMA3A) acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that SEMA3A specifically controls their laminar positioning through PLXNA4. We identify that deep layer INs constitute a major source of SEMA3A in the developing cortex and demonstrate that cell-type specific genetic deletion of SEMA3A in these INs specifically affects the laminar allocation of hINs. These data demonstrate that in the neocortex, deep layer INs control the laminar allocation of hINs into superficial layers.
Evolutionary Based Adaptive Dosing Algorithms: Beware the Cost of Cumulative Risk
Authors: Mistry Hitesh B. 
Published: June 2020

AbstractApplication of theories from ecology to cancer is growing. One such idea involves using drug sensitive cells to control drug resistant cells by cycling treatment on and off based on a marker of tumour burden. Many literature studies have highlighted the benefit of this approach when using time till reaching a certain level of burden as an end-point. These studies though have not considered that patients need to survive up until a certain time-point with a higher level of tumour burden compared to standard dosing to gain this benefit. Within this study once this cumulative cost is accounted for it can be seen that adaptive dosing, counter-intuitively, is likely to lead to poorer prognosis than continuous dosing. This study highlights that evolutionary based adaptive dosing algorithms may not be the “parachute” its protagonists believe it to be.