bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas/Casp8/Bid-axis
Authors: Carlström Karl E , Zhu Keying , Ewing Ewoud , Krabbendam Inge E , Harris Robert A , Falcão Ana Mendanha , Jagodic Maja , Castelo-Branco Gonçalo , Piehl Fredrik 
Published: May 2020

SummaryArrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in Multiple Sclerosis (MS) are associated with disease progression but the underlying mechanism are elusive. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that its loss prevents differentiation into myelinating OLs. Also, Gsta4 appeared to be a novel target for Clemastine, in clinical trial for MS. Over-expression of Gsta4 reduced the expression of Fas and activity along the mitochondria-associated Casp8/Bid-axis in adult pre-OLs from the corpus callosum, together promoting enhanced pre-OL survival during differentiation. The Gsta4-mediated input on apoptosis during adult OL differentiation was further verified in the LPC and EAE model, where Casp8 were reduced in pre-OLs with high Gsta4 expression in an immune response-independent fashion. Our results place Gsta4 as a key regulator of intrinsic mechanisms beneficial for OL differentiation and remyelination, and as a possible target for future MS therapies.
Dynamics of a mutual inhibition between pyramidal neurons compared to human perceptual competition
Authors: Kogo N. , Kern F. B. , Nowotny T. , van Ee R. , van Wezel R. , Aihara T. 
Published: May 2020

AbstractNeural competition plays an essential role in active selection processes of noisy and ambiguous input signals and it is assumed to underlie emergent properties of brain functioning such as perceptual organization and decision making. Despite ample theoretical research on neural competition, experimental tools to allow neurophysiological investigation of competing neurons have not been available. We developed a “hybrid” system where real-life neurons and a computer-simulated neural circuit interacted. It enabled us to construct a mutual inhibition circuit between two real life pyramidal neurons. We then asked what dynamics this minimal unit of neural competition exhibits and compared them to the known behavioral-level dynamics of neural competition. We found that the pair of neurons shows bi-stability when activated simultaneously by current injections. The addition of modelled noise and changes in the activation strength showed that the dynamics of the circuit are strikingly similar to the known properties of bi-stable visual perception.
Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in rheumatoid synovium
Authors: Mokuda Sho , Tokunaga Tadahiro , Masumoto Junya , Sugiyama Eiji 
Published: May 2020

AbstractDetected in December 2019, the coronavirus disease 2019 (COVID-19) has since spread all over the world, resulting in a global pandemic. The disease is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and its symptoms usually include cough, fever, and gastrointestinal problems. Although the prevalence of rheumatoid arthritis (RA) is about 1 % of the global population and RA patients naturally have a chance of acquiring COVID-19 in this pandemic, no studies have considered the expression of angiotensin-converting enzyme 2 (ACE2) (a receptor for SARS-CoV-2) in synovial tissues. Our presenting data revealed that ACE2 expression was elevated in active rheumatoid synovium, and siRNA against STAT3 was able to downregulate ACE2 expression, which was in turn induced by IL-6 signaling.
Plis de passage in the Superior Temporal Sulcus: Morphology and local connectivity
Authors: Bodin C. , Pron A. , Le Mao M. , Régis J , Belin P. , Coulon O. 
Published: May 2020

AbstractWhile there is a profusion of functional investigations involving the superior temporal sulcus (STS), our knowledge of the anatomy of this sulcus is still limited by a large variability across individuals. Several “plis de passage” (PPs), annectant gyri buried inside the fold, can separate the STS into distinct segments and could explain part of the observed variability. However, an accurate characterization is lacking to properly extract and fully understand the nature of PPs. The aim of the present study is twofold:i.to characterize the STS PPs by directly identifying them within individual STS, using the geometry of the surrounding surface and considering both deep and superficial PPs.ii.to test the hypothesis that PPs constitute local increases of the short-range structural connectivity. Performed on 90 subjects from the Human Connectome Project database, our study revealed that PPs constitute surface landmarks that can be identified from the geometry of the STS walls and that they constitute critical pathways of the U-shaped white-matter connecting the two banks of the STS. Specifically, a larger amount of fibers was extracted at the location of PPs compared to other locations in the STS. This quantity was also larger for superficial PPs than for deep buried ones. These findings raise new hypotheses regarding the relation between the cortical surface geometry and structural connectivity, as well as the possible role of PPs in the functional organization of the STS.
Impact of Comorbidities on SARS-CoV-2 Viral Entry-Related Genes
Authors: Breidenbach Joshua D. , Dube Prabhatchandra , Ghosh Subhanwita , Modyanov Nikolai N. , Malhotra Deepak , Dworkin Lance D. , Haller Steven T. , Kennedy David J. 
Published: May 2020

AbstractViral entry mechanisms for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important aspect of virulence. Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2). The distribution of expression of these genes across cell types representing multiple organ systems in healthy individuals has been recently demonstrated. However, comorbidities such as diabetes and cardiovascular disease are highly prevalent in patients with Coronavirus Disease 2019 (COVID-19) and associated with worse outcomes. Whether these conditions contribute directly to SARS-CoV-2 virulence remain unclear. Here we show that the expression levels ofACE2, TMPRSS2and other viral entry-related genes are modulated in target organs of select disease states. In tissues such as heart, which normally expressACE2but minimalTMPRSS2, we found thatTMPRSS2as well as other TTSPs are elevated in individuals with comorbidities vs healthy individuals. Additionally, we found increased expression of viral entry-related genes in the settings of hypertension, cancer or smoking across target organ systems. Our results demonstrate that common comorbidities may contribute directly to SARS-CoV-2 virulence and suggest new therapeutic targets to improve outcomes in vulnerable patient populations.
Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients
Authors: Palaiodimos Leonidas , Chamorro-Pareja Natalia , Karamanis Dimitrios , Li Weijia , Zavras Phaedon D. , Mathias Priyanka , Kokkinidis Damianos G. 
Published: May 2020

AbstractBackgroundInfectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. Our aim was to systematically review and synthesize with a meta-analysis the available observational studies reporting the effect of diabetes in mortality among hospitalized patients with COVID-19.MethodsMedline, Embase, Google Scholar, and medRxiv databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed.Results18,506 patients were included in this meta-analysis (3,713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared to patients without diabetes (OR: 1.65; 95% CI: 1.35-1.96; I2 77.4%). The heterogeneity was high. A study level meta-regression analysis was performed for all the important covariates and no significant interactions were found between the covariates and the outcome of mortality.ConclusionThis meta-analysis shows that that the likelihood of death is 65% higher in diabetic hospitalized patients with COVID-19 compared to non-diabetics. Further studies are needed to assess whether this association is independent or not, as well as to investigate to role of glucose control prior or during the disease.
Increase of non-vaccine human papillomavirus types in a group of HPV-vaccinated Mexican women. Evidence of Pathogenic Strain Replacement
Authors: Cabrera-Becerril Augusto , Alonso Ramiro , Vargas-De-León Cruz , Miramontes Pedro , Romero Pablo , Taniguchi Keiko , Marrero Daniel , Capistrán Marco , Jiménez Sheila , Dávila Sonia , Salcedo Mauricio , Peralta Raúl 
Published: May 2020

AbstractHigh risk HPV infection is the etiological factor of Cervical Cancer (CC) and other types of cancer of epithelial origin. HPV 16 and 18 infections are associated with 70% of CC worldwide. At the present time, there is a vaccine that prevents this infections. In Mexico, the HPV vaccine was introduced in 2009. Even if the current vaccine is effective, some models indicate a possible scenario of Vaccine-induced Pathogen Strain Replacement (VPSR). In this report, we performed the molecular detection of HPV in a group of HPV-vaccinated Mexican women to explore a putative scenario of VPSR. We used biological samples from women who went for their routine Pap. The study included eighteen women older than 18 years of age and HPV-vaccinated. As the number of cases analyzed is relatively small, we supplemented the study with an agent-based direct computer simulation. The outcome of the numerical experiments and the analyzed cases complement each other and show that in three different scenarios, there is an increase in HPV cases approx 10 years after vaccination of the first cohort of women. The prevalence of non-vaccine HPV types increases when compared to prevalence of vaccine HPV types. This result could be interpreted as the phenomenon of Vaccine-induced Pathogenic Strain Replacement.
COVID-19 (SARS-CoV-2) Ventilator Resource Management Using a Network Optimization Model and Predictive System Demand
Authors: Billingham Samuel , Widrick Rebecca , Edwards Nathan J. , Klaus Sybil A. 
Published: May 2020

AbstractThe COVID-19 (SARS-CoV-2) pandemic is overwhelming global healthcare delivery systems due to the exponential spike in cases requiring specialty tests, facilities and equipment, including complex, precision devices like ventilators. In particular, the surge in critically ill patients has revealed a significant deficiency in regional availability of respiratory care ventilators. The authors offer a mathematical framework for ventilator distribution under scarcity conditions using an optimized network model and solver. The framework is interoperable with existing COVID-19 healthcare demand models and scales for different user-defined system sizes, including hospital networks, city, state, regional and national-scale prioritization. The authors’ approach improves current capabilities for medical device resource management within the existing incident command system while accounting for availability of devices, ventilation treatment time periods, disinfection and cleaning between patients, as well as shipping logistics time. The authors present a proof of concept using a high fidelity COVID-19 data set from Colorado, discusses how to scale nationally, and emphasizes the importance of applying ethical human-in-the-loop decision making when using this or similar approaches to managing medical device resources during epidemic emergencies.
Reference genome and demographic history of the most endangered marine mammal, the vaquita
Authors: Morin Phillip A. , Archer Frederick I. , Avila Catherine D. , Balacco Jennifer R. , Bukhman Yury V. , Chow William , Fedrigo Olivier , Formenti Giulio , Fronczek Julie A. , Fungtammasan Arkarachai , Gulland Frances M.D. , Haase Bettina , Heide-Jorgensen Mads Peter , Houck Marlys L. , Howe Kerstin , Misuraca Ann C. , Mountcastle Jacquelyn , Musser Whitney , Paez Sadye , Pelan Sarah , Phillippy Adam , Rhie Arang , Robinson Jacqueline , Rojas-Bracho Lorenzo , Rowles Teri K. , Ryder Oliver A. , Smith Cynthia R. , Stevenson Sacha , Taylor Barbara L. , Teilmann Jonas , Torrance James , Wells Randall S. , Westgate Andrew , Jarvis Erich D. 
Published: May 2020

AbstractThe vaquita is the most critically endangered marine mammal, with fewer than 19 remaining in the wild. First described in 1958, the vaquita has been in rapid decline resulting from inadvertent deaths due to the increasing use of large-mesh gillnets for more than 20 years. To understand the evolutionary and demographic history of the vaquita, we used combined long-read sequencing and long-range scaffolding methods with long- and short-read RNA sequencing to generate a near error-free annotated reference genome assembly from cell lines derived from a female individual. The genome assembly consists of 99.92% of the assembled sequence contained in 21 nearly gapless chromosome-length autosome scaffolds and the X-chromosome scaffold, with a scaffold N50 of 115 Mb. Genome-wide heterozygosity is the lowest (0.01%) of any mammalian species analyzed to date, but heterozygosity is evenly distributed across the chromosomes, consistent with long-term small population size at genetic equilibrium, rather than low diversity resulting from a recent population bottleneck or inbreeding. Historical demography of the vaquita indicates long-term population stability at less than 5000 (Ne) for over 200,000 years. Together, these analyses indicate that the vaquita genome has had ample opportunity to purge highly deleterious alleles and potentially maintain diversity necessary for population health.
Site-specific recombination between inverted target sites generates dicentric/acentric chromosomes
Authors: Titen Simon W. A. , Johnson Makenna T. B. , Capecchi Mario , Golic Kent G. 
Published: May 2020

ABSTRACTSite-specific recombinases are widely used tools for analysis of genetics, development and cell biology, and many schemes have been devised to alter gene expression by recombinase-mediated DNA rearrangements. Because theFRTandloxtarget sites for the commonly used FLP and Cre recombinases are asymmetrical, and must pair in the same direction to recombine, construct design must take into account orientation of the target sites. Both direct and inverted configurations have been used. However, the consequence of recombination between target sites on sister chromatids is frequently overlooked. This is especially consequential with inverted target sites, where exchange between oppositely oriented target sites on sisters will produce dicentric and acentric chromosomes. By using constructs that have inverted target sites inDrosophila melanogasterand in mice, we show here that dicentric chromosomes are produced in the presence of recombinase, and that the frequency of this event is quite high. The negative effects on cell viability and behavior can be significant, and should be considered when using such constructs.
Spatial separation ofStreptomycesaerial mycelium during fermentation enhances secondary metabolite production
Authors: Muralikrishnan Balaji , R J Retnakumar , Ramachandran Ranjit , J S Vinodh , M Nijisha , K B Arun , Paul Laiza , Dastager Syed , Dan Vipin Mohan , Ramakrishnan Ajay Kumar 
Published: May 2020

AbstractConditioning of morphology is an effective technique to enhance secondary metabolite production byStreptomyces. Here we report a novel conditioning method employing glass marbles in batch cultures to enhance secondary metabolite production byStreptomyces sp. The marbles seem to spatially separate aerial and submerged mycelia in the flask which was necessary for the qualitative and quantitative enhancement of metabolite production of secondary metabolites. The method also offers shorter incubation period compared to conventional methods for effective production. Further, using a combination of this method and response surface methodology we could enhance the production of antimycobacterial molecules chrysomycin A and B significantly.ImportanceRediscovery of existing molecules and lack of techniques to induce production of secondary metabolites are the major bottlenecks associated with drug discovery of novel bioactive molecules fromStreptomyces, the major source of marketable drugs today. We found a new method to increase the diversity and quantity of secondary metabolites in twoStreptomycesspecies. This method thus enhances the chance of finding novel active principles fromStreptomyces.
Using Genome-Wide Association Study to Identify Genes and Pathways associated with Hypersensitivity Pneumonitis
Authors: Wang Ling , Millerick Melissa May , Rosenman Kenneth D. , Cui Yuehua , Uhal Bruce , Wang Jianrong , Gerlach John 
Published: May 2020

AbstractBackgroundHypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by an immune response to the inhalation of antigens. Since only a small proportion of individuals exposed to HP-related antigens develop the disease, a genetic variation may play a role in disease development.MethodsIn this small-scale study, 24 patients diagnosed with HP were matched with control group who shared the patient’s environment and were exposed to the same HP-associated antigens. Logistic regression was employed to identify Single-Nucleotide Polymorphisms (SNPs) associated with HP. Next genes associated with HP were identified using sequence kernel association test (SKAT) analysis. Last, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Oncology (GO) enrichment analysis were employed to find HP signaling pathways using SNPs coded on genes and on non-coding genes, respectively.ResultsGiven the small sample size, no single SNPs or genes were identified to be significantly associated with HP after adjustment for multiple testing. After P-value adjustment, the KEGG and GO pathway enrichment analysis identified 11 and 20 significant pathways respectively using SNPs coded on genes. Among these pathways, Cell cycle, Proteasome and Base excision repair had previously reported to be associated with lung function.ConclusionThis is the first GWAS study identifying genetic factors associated with HP. Although no significant associations at SNPs/gene level were identified, there were significant pathways that are identified associated with HP which need further investigation in large cohorts.
Searching for biological feedstock material: 3D printing of wood particles from house borer and drywood termite frass
Authors: Plarre Rudy , Zocca Andrea , Spitzer Andrea , Benemann Sigrid , Gorbushina Anna A. , Li Yuexuan , Wilbig Janka , Günste Jens 
Published: May 2020

AbstractFrass (fine powdery refuse or fragile perforated wood produced by the activity of boring insects) of larvae of the European house borer and of drywood termites was tested as a natural and novel feedstock for 3D-printing of wood-based materials. Small particles produced by the drywood termiteIncisitermes marginipennisand the European house borer (EHB)Hylotrupes bajulusduring feeding in construction timber, were used. Frass is a powdery material of particularly consistent quality that is essentially biologically processed wood mixed with debris of wood and faeces. The filigree-like particles flow easily permitting the build-up of wood-based structures in a layer wise fashion using the Binder Jetting printing process. The quality of powders produced by different insect species was compared along with the processing steps and properties of the printed parts. Drywood termite frass with a HR = 1.1 with ρBulk = 0.67 g.cm-3and ρTap = 0.74 g.cm-3was perfectly suited to deposition of uniformly packed layers in 3D printing. We suggest that a variety of naturally available feedstocks could be used in environmentally responsible approaches to scientific material sciences/additive manufacturing.
SARS-CoV-2 envelope protein topology in eukaryotic membranes
Authors: Duart Gerard , García-Murria Ma Jesús , Grau Brayan , Acosta-Cáceres José M. , Martínez-Gil Luis , Mingarro Ismael 
Published: May 2020

ABSTRACTCoronavirus E protein is a small membrane protein found in the virus envelope. Different coronavirus E proteins share striking biochemical and functional similarities, but sequence conservation is limited. In this report, we studied the E protein topology from the new SARS-CoV-2 virus both in microsomal membranes and in mammalian cells. Experimental data reveal that E protein is a single-spanning membrane protein with the N-terminus being translocated across the membrane, while the C-terminus is exposed to the cytoplasmic side (Ntlum/Ctcyt). The defined membrane protein topology of SARS-CoV-2 E protein may provide a useful framework to understand its interaction with other viral and host components and establish the basis to tackle the pathogenesis of SARS-CoV-2.
Assessment of ACE2, CXCL10 and Their co-expressed Genes: An In-silico Approach to Evaluate the Susceptibility and Fatality of Lung Cancer Patients towards COVID-19 Infection
Authors: Mahmood Tousif Bin , Chowdhury Afrin Sultana , Hasan Mehedee , Aakil Md. Mezbah-Ul-Islam , Hossan Mohammad Imran 
Published: May 2020

AbstractBackgroundCOVID-19 is a recent pandemic that started to spread out worldwide from Wuhan, China. This disease is caused by a newly discovered strain of the coronavirus, namely SARS CoV-2. Lung cancer patients are reported to be more susceptible to COVID-19 infection. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted two most crucial biomarkers of COVID-19, ACE2 and CXCL10. ACE2 plays a vital role in the SARS CoV-2 entry into the host cell while CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm.MethodsFirstly, we used the TIMER, UALCAN and GEPIA2 databases to analyze the expression and correlation of ACE2 and CXCL10 in LUAD and LUSC. After that, using the cBioPortal database, we performed an analytical study to determine the genetic changes in ACE2 and CXCL10 protein sequences that are responsible for lung cancer development. Finally, we analyzed different functional approaches of ACE2, CXCL10 and their co-expressed genes associated with lung cancer and COVID-19 development by using the PANTHER database.ResultsInitially, we observed that ACE2 and CXCL10 are mostly overexpressed in LUAD and LUSC. We also found the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences. Lastly, by doing the functional assessment of the targeted genes, we identified that ACE2 and CXCL10 along with their commonly co-expressed genes are respectively involved in the binding activity and immune responses in case of lung cancer and COVID-19 infection.ConclusionsFinally, on the basis of this systemic analysis, we came to the conclusion that ACE2 and CXCL10 are possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.