bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 RNA shedding in recovered COVID-19 cases and the presence of antibodies against SARS-CoV-2 in recovered COVID-19 cases and close contacts
Authors: Chirathaworn Chintana , Sripramote Manit , Chalongviriyalert Piti , Jirajariyavej Supunee , Kiatpanabhikul Phatharaporn , Saiyarin Jatuporn , Soudon Chulikorn , Thienfaidee Orawan , Na Ayuthaya Thitisan Palakawong , Brukesawan Chantapat , Chaiwanichsiri Dootchai , Intharasongkroh Duangnapa , Wanlapakorn Nasamon , Chansaenroj Jira , Puenpa Jiratchaya , Yorsaeng Ritthideach , Thitithanyanont Arunee , Kitphati Rungrueng , Mungaomklang Anek , Nagavajara Pijaya , Poovorawan Yong 
Published: July 2020

AbstractCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 emerged in December 2019 and has spread globally. Although Thailand has been effective at controlling the spread of COVID-19, disease surveillance and information on antibody responses in infected cases and close contacts are needed because there is still no specific treatment or vaccine available. We investigated 217 recovered COVID-19 cases to monitor their viral RNA shedding and production of antibodies against SARS-CoV-2. The presence of antibodies in blood samples from 308 close contacts of COVID-19 cases was also determined. Viral RNA was still detectable in 6.6 % of recovered COVID-19 cases. The most prolonged duration of viral RNA shedding detected in this study was 105 days. IgM, IgG, and IgA antibodies against SARS-CoV-2 were detected in 13.82, 88.48, and 83.41 % of the recovered cases 4–12 weeks after disease onset, respectively. Although the patients had recovered from their illness, the levels of antibodies detected showed association with their symptoms during their stay in hospital. Fifteen of the 308 contacts (4.87 %) of COVID-19 cases tested positive for IgG antibodies. The presence of antibodies against SARS-CoV-2 suggested that there was viral exposure among close contacts. Viral clearance and the pattern of antibody responses in infected individuals are both crucial for effectively combatting SARS-CoV-2. Our study provides additional information on the natural history of this newly emerging disease related to both natural host defenses and a strategy for vaccine development.
CXCR5gene expression in human lymph node CD8+T cells is regulated by DNA methylation and nucleosomal occupancy
Authors: Ogunshola Funsho J. , Smidt Werner , Naidoo Anneta F. , Nkosi Thandeka , Ngubane Thandekile , Khaba Trevor , Baiyegunhi Omolara O. , Rasehlo Sam , Jajbhay Ismail , Dong Krista L. , Ramsuran Veron , Pansegrouw Johan , Ndung’u Thumbi , Walker Bruce D. , de Oliveria Tulio , Ndhlovu Zaza M. 
Published: July 2020

AbstractCD8+T cells play an important role in viral and tumour control. However, in human lymph nodes (LNs), only a small subset of CD8+T cells called follicular CD8+T cells (fCD8s) expresses CXCR5, the chemokine receptor required for cell migration into B cell follicles, thought to promote immune evasion. Here we obtained LNs from HIV infected persons to investigate regulation of CXCR5 expression in lymphoid CD8+T cells, and compared this to the more abundant CXCR5 expressing T follicular CD4+helper cells (GCTfh). Our results show that DNA hypermethylation and closed chromatin at the transcriptional start site (TSS) prevent CXCR5 expression in non-fCD8s. We also found that greater nucleosomal density at the CXCR5 TSS could be responsible for reduced CXCR5 expression in fCD8s relative to GCTfh. Together, these data provide critical insights into both the underlying molecular mechanisms that repress CXCR5 expression in non-fCD8s and the plausible mechanism responsible for the low CXCR5 expression in fCD8s, with implications for HIV cure strategies.Author SummaryA paucity of CD8+T cells that express CXCR5, the chemokine receptor critical for entering the B cell follicles of secondary lymphoid tissues have recently been described. Animal studies have revealed transcriptional networks that govern the expression of CXCR5 in CD8+T cells. However, it is not known if similar or additional networks regulate the expression of CXCR5 in human CD8+T cells. In this study, we demonstrated that DNA methylation coupled with chromatin compaction at the transcriptional start site (TSS) ofCXCR5gene prevent the expression CXCR5 in human CD8+T cells. In addition, we observed greater nucleosomal occupancy at the TSS ofCXCR5gene which could impact expression levels of CXCR5 in human CXCR5+CD8+T cells. This study revealed multitiered epigenetic mechanisms that repress CXCR5 expression in human CD8+T cells, with implications for HIV cure strategy or eradication of B cell-derived tumours.
Phosphatidylinositol-3 kinase activity controls survival and stemness of zebrafish hematopoietic stem/progenitor cells
Authors: Blokzijl-Franke Sasja , Ponsioen Bas , Schulte-Merker Stefan , Herbomel Philippe , Kissa Karima , Choorapoikayil Suma , den Hertog Jeroen 
Published: July 2020

AbstractHematopoietic Stem and Progenitor Cells (HSPCs) are multipotent cells giving rise to all blood lineages during life. HSPCs emerge from the ventral wall of the dorsal aorta (VDA) during a specific timespan in embryonic development through endothelial hematopoietic transition (EHT). We investigated the ontogeny of HSPCs in mutant zebrafish embryos lacking functional pten, an important tumor suppressor with a central role in cell signaling. Through in vivo live imaging, we discovered that inptenmutant embryos a proportion of the HSPCs died upon emergence from the VDA, an effect rescued by inhibition of phosphatidylinositol-3 kinase (PI3K). Surprisingly, inhibition of PI3K in wild type embryos also induced HSPC death. Surviving HSPCs colonized the caudal hematopoietic tissue (CHT) normally and committed to all blood lineages. Single cell RNA sequencing indicated that inhibition of PI3K enhanced survival of multi-potent progenitors, whereas the number of HSPCs with more stem-like properties was reduced. At the end of the definitive wave, loss of Pten caused a shift to more restricted progenitors at the expense of HSPCs. We conclude that PI3K signaling tightly controls HSPCs survival and both up- and downregulation of PI3K signaling reduces stemness of HSPCs.2Key pointsLoss of Pten and inhibition of PI3K induced apoptosis of hematopoietic stem/progenitor cells upon endothelial to hematopoietic transitionSurviving hematopoietic stem/progenitor cells committed to all blood lineages but displayed reduced stemness
The mechanism of selective kinesin inhibition by kinesin binding protein
Authors: Atherton Joseph , Hummel Jessica J. A. , Olieric Natacha , Locke Julia , Peña Alejandro , Rosenfeld Steven S. , Steinmetz Michel O. , Hoogenraad Casper C. , Moores Carolyn A. 
Published: July 2020

AbstractSubcellular compartmentalisation is necessary for eukaryotic cell function. Spatial and temporal regulation of kinesin activity is essential for building these local environments via control of intracellular cargo distribution. Kinesin binding protein (KBP) interacts with a subset of kinesins via their motor domains, inhibits their microtubule (MT) attachment and blocks their cellular function. However, its mechanisms of inhibition and selectivity have been unclear. Here we use cryo-electron microscopy to reveal the structure of KBP and of a KBP-kinesin motor domain complex. KBP is a TPR-containing, crescent-shaped right-handed α-solenoid that sequesters the tubulin-binding surface of the kinesin motor domain, structurally distorting the motor domain and sterically blocking MT attachment. KBP uses its α-solenoid concave face and edge loops to bind the kinesin motor domain and selective mutation of this extended binding surface disrupts KBP inhibition of kinesin transport in cells. The KBP-interacting surface of the motor domain contains motifs exclusively conserved in KBP-interacting kinesins, providing a basis for kinesin selectivity.
DEXOM: Diversity-based enumeration of optimal context-specific metabolic networks
Authors: Rodríguez-Mier Pablo , Poupin Nathalie , de Blasio Carlo , Le Cam Laurent , Jourdan Fabien 
Published: July 2020

AbstractThe correct identification of metabolic activity in tissues or cells under different environmental or genetic conditions can be extremely elusive due to mechanisms such as post-transcriptional modification of enzymes or different rates in protein degradation, making difficult to perform predictions on the basis of gene expression alone. Context-specific metabolic network reconstruction can overcome these limitations by leveraging the integration of multi-omics data into genome-scale metabolic networks (GSMN). Using the experimental information, context-specific models are reconstructed by extracting from the GSMN the sub-network most consistent with the data, subject to biochemical constraints. One advantage is that these context-specific models have more predictive power since they are tailored to the specific organism and condition, containing only the reactions predicted to be active in such context. A major limitation of this approach is that the available information does not generally allow for an unambiguous characterization of the corresponding optimal metabolic sub-network, i.e., there are usually many different sub-network that optimally fit the experimental data. This set of optimal networks represent alternative explanations of the possible metabolic state. Ignoring the set of possible solutions reduces the ability to obtain relevant information about the metabolism and may bias the interpretation of the true metabolic state. In this work, we formalize the problem of enumeration of optimal metabolic networks, we implement a set of techniques that can be used to enumerate optimal networks, and we introduceDEXOM, a novel strategy for diversity-based extraction of optimal metabolic networks. Instead of enumerating the whole space of optimal metabolic networks, which can be computationally intractable,DEXOMsamples solutions from the set of optimal metabolic sub-networks maximizing diversity in order to obtain a good representation of the possible metabolic state. We evaluate the solution diversity of the different techniques using simulated and real datasets, and we show how this method can be used to improve in-silico gene essentiality predictions inSaccharomyces Cerevisiaeusing diversity-based metabolic network ensembles. Both the code and the data used for this research are publicly available on GitHub1.
H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation
Authors: Dong Jie , LeBlanc Chantal , Poulet Axel , Mermaz Benoit , Villarino Gonzalo , Webb Kimberly M. , Joly Valentin , Mendez Josefina , Voigt Philipp , Jacob Yannick 
Published: July 2020

AbstractIn plants, genome stability is maintained during DNA replication by the H3.1K27 methyltransferases ATXR5 and ATXR6, which catalyze the deposition of K27me1 on replicationdependent H3.1 variants. Loss of H3.1K27me1 inatxr5 atxr6double mutants leads to heterochromatin defects, including transcriptional de-repression and genomic instability, but the molecular mechanisms involved remain largely unknown. In this study, we identified the conserved histone acetyltransferase GCN5 as a mediator of transcriptional de-repression and genomic instability in the absence of H3.1K27me1. GCN5 is part of a SAGA-like complex in plants that requires ADA2b and CHR6 to mediate the heterochromatic defects ofatxr5 atxr6mutants. Our results show that Arabidopsis GCN5 acetylates multiple lysine residues on H3.1 variantsin vitro,but that H3.1K27 and H3.1K36 play key roles in inducing genomic instability in the absence of H3.1K27me1. Overall, this work reveals a key molecular role for H3.1K27me1 in maintaining genome stability by restricting histone acetylation in plants.
Characterization of a membrane enzymatic complex for heterologous production of poly-γ-glutamate inE. coli
Authors: Nascimento Bruno Motta , Nair Nikhil U. 
Published: July 2020

ABSTRACTPoly-γ-glutamic acid (PGA) produced by manyBacillusspecies is a polymer with many distinct and desirable characteristics. However, the multi-subunit enzymatic complex responsible for its synthesis, PGA Synthetase (PGS), has not been well characterized yet, in native nor in recombinant contexts. Elucidating structural and functional properties are crucial for future engineering efforts aimed at altering the catalytic properties of this enzyme. This study focuses on expressing the enzyme heterologously in theEscherichia colimembrane and characterizing localization, orientation, and activity of this heterooligomeric enzyme complex. InE. coli, we were able to produce high molecular weight PGA polymers with minimal degradation at titers of approximately 13 mg/L in deep-well microtiter batch cultures. Using fusion proteins, we observed, for the first time, the association and orientation of the different subunits with the inner cell membrane. These results elucidate provide fundamental structural information on this poorly studied enzyme complex and will aid future fundamental studies and engineering efforts.HIGHLIGHTSSuccessfully expressed active poly-γ-glutamate synthetase (PGS) inE. coli.Confirmed PGS localization at inner membrane ofE. coli.Elucidated topology of PGS components inE. colimembrane.Culture and expression in microplates might allow future screening of a high number of samples.Faster production of poly-γ-glutamate inE. colisupernatant compared toB. subtilis.
Biological and molecular characterization of six Shiga toxin-producingEscherichia coli(STEC) strains encoding the stx2gene in Colombia
Authors: Arango-Gil Brayan Stiven , Peña-Buitrago Sebastián , Castaño-Osorio Jhon Carlos , Granobles-Velandia Claudia Viviana 
Published: July 2020

ABSTRACTShiga toxin-producingEscherichia coli(STEC) is a bacterial pathogen that cause diarrhea and severe human diseases. Its principal virulence factor are the Shiga toxins Stx1 and Stx2 which have been identified diverse subtypes considered to be responsible for severe complications of STEC infection. These toxins are encoded in temperate bacteriophages and their expression is linked to phage lithic cycle, which is regulated by late genes and the Q anti-terminator protein. The aim of this study was to characterize biologically and molecularly STEC strains encoding stx2gene isolated from cattle feces in Colombia. We selected six STEC strains, which were evaluated its Stx production, the Stx2subtypes, induction of the lithic cycle of bacteriophages and its late region. The results evidenced two highlighted strains with high levels of Stx production and induction of the lithic cycle, compared with the others. Likewise, the strains evaluated showed three Stx2subtypes: Stx2a, Stx2c, and Stx2d. Regarding the late region, most of the strains carried theqO111allele and only one strain showed differences in theninGgene. Although the sample was limited, variability was observed in the Stx production assay, induction of the lithic cycle, Stx2subtypes and late region of the phages, which could indicate the diversity of the phages carrying STEC strains in Colombia.
Resveratrol shortens the chronological lifespan ofSaccharomyces cerevisiaeby a pro-oxidant mechanism
Authors: Canedo-Santos Juan Carlos , Mora-Martinez Iridian , Gutierrez-Garcia Ingrid Karina , Ramirez-Romero Maria Guadalupe , Madrigal-Perez Luis Alberto 
Published: July 2020

AbstractResveratrol consumption has linked with normalization of the risk factors of some diseases such as colon cancer and type 2 diabetes. The antioxidant phenotype caused by resveratrol has recognized as a key piece in the health benefits exerted by this phytochemical. Although the antioxidant activity showed by resveratrol has attributed at the moleculeper se, recent evidence indicates that the antioxidant effect occasioned by resveratrol could be associated with a pro-oxidant mechanism. The hypothesis that resveratrol inhibits complex III of the electron transport chain as its main target suggests that resveratrol increases reactive oxygen species (ROS) generation produces via reverse electron transport. This idea also explains that cells respond to the oxidative damage caused by resveratrol, inducing their antioxidant systems. The free radical theory of aging postulates that organisms age due to the accumulation of the harmful effects of ROS in cells. For these reasons, we hypothesize that resveratrol shortens the chronological life span (CLS) ofSaccharomyces cerevisiaedue to a pro-oxidant activity. Herein, we provide evidence that 100 μM resveratrol supplementation at 5% glucose: 1) shorted the CLS ofCTT1andYAP1genes deleted strains; 2) decreased the H2O2release in the WT strain, and maintain unaltered the H2O2release in thectt1Δ strain; 3) lessened exponential growth ofctt1Δ strain, which was reverted with the adding of GSH; 4) increased catalase activity in the WT strain, a phenotype that was not observed in thectt1Δ strain. Altogether, these results indicate that resveratrol decreases CLS by a pro-oxidant mechanism.
Rapid tolerance to morphine in the myenteric neurons of the small intestine is independent of β-arrestin-2 and mediated by PKC
Authors: Muchhala Karan H. , Jacob Joanna C. , Alam Imran , Hasan Shahzeb , Khan Aliyeen , Kang Minho , Dewey William L. , Akbarali Hamid I. 
Published: July 2020

AbstractBackground and PurposeG-protein biased μ-opioid agonists against β-arrestin-2 activation are being investigated to reduce adverse effects. While opioid tolerance is strongly linked to the development of dependence, there is a dissociation between the two phenomena in the gut as tolerance does not develop to opioid-induced constipation, but diarrhea still manifests upon withdrawal. Here, we investigated the mechanism by which morphine tolerance in the small intestine develops.Experimental ApproachMechanism of morphine tolerance in the small intestine was evaluatedin vivoand at the neuronal level. Whole-cell patch clamp electrophysiology was used to investigate tolerance in individual ileum myenteric neurons. Rate of morphine tolerance development in the small intestine was assessed against peripheral antinociception and whole gut transit.Key ResultsTolerance develops to inhibition of small intestinal motility after one day of morphine exposure, and is more rapid compared to peripheral antinociception and constipation in chronic morphine-treated mice. Morphine tolerance was reversed by the PKC inhibitor, Tamoxifen, but not by β-arrestin-2 deletion. Similarly, β-arrestin-2 deletion did not prevent morphine tolerance to inhibition of neuronal excitability in ileum myenteric neurons. However, neuronal tolerance was attenuated by inhibiting PKC.Conclusions and ImplicationsUnlike antinociceptive tolerance, rapid morphine tolerance in the small intestine is independent of β-arrestin-2 but is PKC-mediated. These findings reveal a potential mechanism for differences in the rates of tolerances to opioids, implicate myenteric neurons of the ileum as the primary cause for opioid-induced withdrawal effects and suggest that undesired gastrointestinal effects will persist with biased opioid agonist use.SummaryWhat is already known:Tolerance does not develop to chronic-opioid-induced constipation but diarrhea is produced upon withdrawalNovel G-protein biased agonists that preclude β-arrestin-2 activation at the μ-opioid receptor are in developmentWhat this study adds:Morphine tolerance in the ileum develops systemically and in individual myenteric neurons independent of β-arrestin-2Morphine tolerance in the small intestine develops before antinociception and is reversed by PKC inhibitionClinical significance:Clinical use of G-protein biased opioid agonists will not prevent tolerance development in the ileumTolerance in ileum myenteric neurons might be the basis of opioid-induced withdrawal in the gut
A preliminary model to describe the transmission dynamics of Covid-19 between two neighboring cities or countries
Authors: Isea Raúl 
Published: July 2020

AbstractWe present a mathematical model that would allow one to describe the transmission dynamics of Covid-19 between two neighboring cities or countries. This model is analyzed both analytical and numerically. It is a preliminary model because it assumes that the migration rate and the mortality rate are constant over time. Despite these simplifications, only two of the four equilibrium conditions were deduced from the system of equations proposed in this paper. Finally, we show an example the transmission dynamics between Portugal and Spain according to the cases registered before June 3, 2020.
Genetic risk score for ovarian cancer based on chromosomal-scale length variation
Authors: Toh Chris , Brody James P. 
Published: July 2020

AbstractIntroductionTwin studies indicate that a substantial fraction of ovarian cancers should be predictable from genetic testing. Genetic risk scores can stratify women into different classes of risk. Higher risk women can be treated or screened for ovarian cancer, which should reduce overall death rates due to ovarian cancer. However, current ovarian cancer genetic risk scores, based on SNPs, do not work that well. We developed a genetic risk score based on structural variation, quantified by variations in the length of chromosomes.MethodsWe evaluated this genetic risk score using data collected by The Cancer Genome Atlas. From this dataset, we synthesized a dataset of 414 women who had ovarian serous carcinoma and 4225 women who had no form of ovarian cancer. We characterized each woman by 22 numbers, representing the length of each chromosome in their germ line DNA. We used a gradient boosting machine, a machine learning algorithm, to build a classifier that can predict whether a woman had been diagnosed with ovarian cancer in this dataset.ResultsThe genetic risk score based on chromosomal-scale length variation could stratify women such that the highest 20% had a 160x risk (95% confidence interval 50x-450x) compared to the lowest 20%. The genetic risk score we developed had an area under the curve of the receiver operating characteristic curve of 0.88 (estimated 95% confidence interval 0.86-0.91).ConclusionA genetic risk score based on chromosomal-scale length variation of germ line DNA provides an effective means of predicting whether or not a woman will develop ovarian cancer.
SARS-CoV-2 Transmission in Alberta, British Columbia, and Ontario, Canada, January 1-July 6, 2020
Authors: Fung Isaac Chun-Hai , Hung Yuen Wai , Ofori Sylvia K. , Muniz-Rodriguez Kamalich , Lai Po-Ying , Chowell Gerardo 
Published: July 2020

AbstractObjectiveTo investigate COVID-19 epidemiology in Alberta, British Columbia and Ontario, Canada.MethodsWe calculated the incidence rate ratio (January 1—July 6, 2020) between the 3 provinces, and estimated time-varying reproduction number, Rt, starting from March 1, using EpiEstim package in R.ResultsUsing British Columbia as a reference, the incidence rate ratios in Alberta and Ontario are 3.1 and 4.3 among females, and 3.4 and 4.0 among males. In Ontario, Rt fluctuated ~1 in March, reached values >1 in early and mid-April, then dropped <1 in late April and early May. Rt rose to ~1 in mid-May and then remained <1 from late May through early July. In British Columbia, Rt dropped <1 in early April, but it increased towards the end of April. Rt <1 in May while it fluctuated around 1.0 in June and early July. In Alberta, Rt > 1 in March; Rt dropped in early April and rose again in late April. In much of May, Rt <1, but Rt increases in early June and fluctuates ~1 since mid-June.ConclusionsRt wavering around 1.0 indicated that three provinces of Canada have managed to achieve limited onward transmission of SARS-CoV-2 as of early July 2020.