bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance to different antibiotics in clinical isolates ofEnterococcus faecalisobtained from urine cultures of patients with urinary tract infection
Authors: Rodríguez Mariana Islas , Esquivel José Carlos Valencia , Peña Silvia Patricia Rodríguez , de Freitas Elisangela Oliveira , Villegas Jorge Angel Almeida 
Published: September 2020

AbstractObjectiveTo identify patterns of resistance against various antibiotics inEnterococcus faecalisin urinary tract infections in a population of the Toluca valley, MexicoMethods155 samples were collected from patients with suspected urinary tract infection without exclusion criteria such as age or gender. Automated equipment was used for the identification of the etiological agent and sensitivity tests.Results80 positive cultures were obtained, of which 20 strains belong to Enterococcus faecalis, which show 100% sensitivity for penicillins, linezolid, vancomycin, bacitracin, a high pattern of sensitivity for quinolones, and a high pattern of resistance to rifampicin, erythromycin and 100% resistance in tetracyclineConclusionIt shows 100% sensitivity to penicillins, vancomycin and linezolid, first-line treatments and for cases of infection complicated by Enterococci. And 100% resistance for tetracycline and high resistance patterns for erythromycin and rifampin.
Epidemiology of COVID-19 vs. Influenza: Differential Failure of COVID-19 Mitigation among Hispanics
Authors: Trick William E. , Badri Sheila , Doshi Kruti , Zhang Huiyuan , Rezai Katayoun , Hoffman Michael J. , Weinstein Robert A. 
Published: September 2020

ABSTRACTBACKGROUNDDuring the early phases of the COVID-19 pandemic, predominantly African-American or Hispanic communities were disproportionately impacted. We sought to better understand the epidemiology of COVID-19 among hospitalized Hispanic patients by comparing individual and census-tract level characteristics of patients diagnosed with COVID-19 to those diagnosed with influenza, another viral infection with respiratory transmission. We evaluated the temporal changes in epidemiology across race-ethnicity related to a shelter-in-place mandate.METHODSWe evaluated patients hospitalized at Cook County Health, the safety-net health system for the Chicago metropolitan area. Among self-identified hospitalized Hispanic patients, we compared those with influenza (2019-2020 influenza season) to COVID-19 infection during March 16, 2020 through May 11, 2020. We used multivariable analysis to identify differences in individual and census-tract level characteristics between the two groups.RESULTSRelative to non-Hispanic blacks and whites, COVID-19 rapidly increased among Hispanics during promotion of social-distancing policies. Whereas non-Hispanic blacks were more likely to be hospitalized for influenza, Hispanic patients predominated among COVID-19 infections (40% relative increase compared to influenza). In the comparative analysis of influenza and COVID-19, Hispanic patients with COVID-19 were more likely to reside in census tracts with higher proportions of residents with the following characteristics: Hispanic; no high school diploma; non-US citizen; limited English speaking ability; employed in manufacturing or construction; and, overcrowding. By multivariable analysis, Hispanic patients hospitalized with COVID-19 compared to those with influenza were more likely to be male (adjusted OR=1.8; 95% CI 1.1 to 2.9) or obese (aOR=2.5; 95% CI 1.5 to 4.2), and to reside in a census tract with ≥40% of residents without a high-school diploma (aOR=2.5; 95% CI 1.3 to 4.8).CONCLUSIONSThe rapid and disproportionate increase in COVID-19 hospitalizations among Hispanics after the shelter-in-place mandate indicates that public health strategies were inadequate in protecting this population. In particular, those residing in neighborhoods with lower levels of educational attainment.
A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody
Authors: Wu Nicholas C. , Yuan Meng , Bangaru Sandhya , Huang Deli , Zhu Xueyong , Lee Chang-Chun D. , Turner Hannah L. , Peng Linghang , Yang Linlin , Nemazee David , Ward Andrew B. , Wilson Ian A. 
Published: September 2020

ABSTRACTEpitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that can cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential for cross-neutralizing epitopes on SARS-like viruses.
Antimetabolic cooperativity with the clinically approved kidrolase and tyrosine kinase inhibitors to eradicate cml stem cells
Authors: Trinh Anne , Khamari Raeeka , Fovez Quentin , Mahon François-Xavier , Turcq Béatrice , Bouscary Didier , Maboudou Patrice , Joncquel Marie , Coiteux Valérie , Germain Nicolas , Laine William , Dekiouk Salim , Ghesquiere Bart , Idziorek Thierry , Quesnel Bruno , Kluza Jerome , Marchetti Philippe 
Published: September 2020

AbstractLong-term treatment with tyrosine kinase inhibitors (TKI) represents an effective treatment for chronic myeloid leukemia (CML) and discontinuation of TKI therapy is now proposed to patient with deep molecular responses. However, evidence demonstrating that TKI are unable to fully eradicate dormant leukemic stem cells indicate that new therapeutic strategies are needed to prevent molecular relapses. We investigated the metabolic pathways responsible for CML surviving to Imatinib exposure and its potential therapeutic utility to improve the efficiency of TKI against CML stem cells. Using complementary cell-based techniques, we demonstrated that TKI suppressed glycolysis in a large panel of BCR-ABL1 + cell lines as well as in primary CD34+ stem-like cells from CML patients. However, compensatory glutamine-dependent mitochondrial oxidation supported ATP synthesis and CML cell survival. Glutamine metabolism was inhibited by L-asparaginases such as Kidrolase without inducing predominant CML cell death. Clinically relevant concentrations of TKI render CML progenitors and stem cells susceptible to Kidrolase. The combination of TKI with L-asparaginase reactivated the intinsic apoptotic pathway leading to efficient CML cell death. Thus, targeting glutamine metabolism with the clinically-approved drug Kidrolase, in combination with TKI that suppress glycolysis represents an effective and widely applicable therapeutic strategy for eradicating CML stem cells.
Modelling locust foraging: How and why food affects hopper band formation
Authors: Georgiou Fillipe , Buhl Jerome , Green J.E.F. , Lamichhane Bishnu , Thamwattana Natalie 
Published: September 2020

AbstractLocust swarms are a major threat to agriculture, affecting every continent except Antarctica and impacting the lives of 1 in 10 people. Locusts are short horned grasshoppers that exhibit two behaviour types depending on their local population density. These are; solitarious, where they will actively avoid other locusts, and gregarious where they will seek them out. It is in this gregarious state that locusts can form massive and destructive flying swarms or plagues. However, these swarms are usually preceded by the formation of hopper bands by the juvenile wingless locust nymphs. It is thus important to understand the hopper band formation process to control locust outbreaks.On longer time-scales, environmental conditions such as rain events synchronize locust lifecycles and can lead to repeated outbreaks. On shorter time-scales, changes in resource distributions at both small and large spatial scales have an effect on locust gregarisation. It is these short time-scale locust-resource relationships and their effect on hopper band formation that are of interest.In this paper we investigate not only the effect of food on both the formation and characteristics of locust hopper bands but also a possible evolutionary explanation for gregarisation in this context. We do this by deriving a multi-population aggregation equation that includes non-local inter-individual interactions and local inter-individual and food interactions. By performing a series of numerical experiments we find that there exists an optimal food width for locust hopper band formation, and by looking at foraging efficiency within the model framework we uncover a possible evolutionary reason for gregarisation.Author summaryLocusts are short horned grass hoppers that live in two diametrically opposed behavioural states. In the first, solitarious, they will actively avoid other locusts, whereas the second, gregarious, they will actively seek them out. It is in this gregarious state that locusts form the recognisable and destructive flying adult swarms. However, prior to swarm formation juvenile flightless locusts will form marching hopper bands and make their way from food source to food source. Predicting where these hopper bands might form is key to controlling locust outbreaks.Research has shown that changes in food distributions can affect the transition from solitarious to gregarious. In this paper we construct a mathematical model of locust-locust and locust-food interactions to investigate how and why isolated food distributions affect hopper band formation. Our findings suggest that there is an optimal food width for hopper band formation and that being gregarious increases a locusts ability to forage when food width decreases.
Prevailing role of mucosal immunoglobulins and B cells in teleost skin immune responses to bacterial infection
Authors: Zhang Xiao-Ting , Yu Yong-Yao , Xu Hao-Yue , Huang Zhen-Yu , Liu Xia , Cao Jia-Feng , Meng Kai-Feng , Wu Zheng-Ben , Han Guang-Kun , Zhan Meng-Ting , Ding Li-Guo , Kong Wei-Guang , Li Nan , Takizawa Fumio , Oriol Sunyer J , Xu Zhen 
Published: September 2020

AbstractThe skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent immunoglobulin (Ig) in SALT have only been reported upon infection with a parasite. However, very little is known about the types of B cells and Igs responding to bacterial infection in the teleost skin mucosa, as well as the inductive or effector role of the SALT in such responses. To address these questions, here we analyzed the immune response of trout skin upon infection with one of the most widespread fish skin bacterial pathogens,Flavobacterium columnare. This pathogen induced strong skin innate immune and inflammatory responses at the initial phases of infection. More critically, we found that the skin mucus of fish having survived the infection contained significant IgT-but not IgM- or IgD-specific titers against the bacteria. Moreover, wedemonstrate the local proliferation and production of IgT+B-cells and specific IgT titers respectively within the SALT upon bacterial infection. Thus, our findings represent the first demonstration that IgT is the main Ig isotype induced by the skin mucosa upon bacterial infection, and that because of the large surface of the skin, its SALT probably represents a prominent IgT inductive site in fish.
CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute pancreatitis
Authors: Zhang Hongxia , Zeng Lingbing , Liu Qiong , Jin Guilin , Zhang Jieyu , Li Zengbin , Xu Yilian , Huang Xiaotian 
Published: September 2020

AbstractCoxsackievirus B3 (CVB3) belongs to the genusEnterovirusof the familyPicornaviridaeand can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Through yeast two-hybrid, co-immunoprecipitation, and confocal microscopy, we show that Menage a trois 1 (MAT1), a subunit of the Cdk-Activating Kinase (CAK) complex involved in cell proliferation and transcription, is a novel interaction protein with CVB3 VP1. Moreover, CVB3 VP1 inhibited MAT1 accumulation and localization, thus interfering with its interaction with CDK7. Furthermore, CVB3 VP1 could suppress CAK complex enzymic phosphorylation activity towards RNA Pol II and CDK4/6, direct substrates of CAK. VP1 also suppresses phosphorylation of retinoblastoma protein (pRb), an indirect CAK substrate, especially at phospho-pRb Ser780and phospho-pRb Ser807/811residues, which are associated with cell proliferation. Finally, we present evidence using deletion mutants that the C-terminal domain (VP1-D8, 768-859aa) is the minimal VP1 region required for its interaction with MAT1, and furthermore, VP1-D8 alone was sufficient to arrest cells in G1/S phase as observed during CVB3 infection. Taken together, we demonstrate that CVB3 VP1 can inhibit CAK complex assembly and activity through direct interaction with MAT1, to block MAT1-mediated CAK-CDK4/6-Rb signaling, and ultimately suppress cell proliferation in pancreatic cells. These findings substantially extend our basic understanding of CVB3-mediated pancreatitis, providing strong candidates for strategic therapeutic targeting.
Identification of microRNAs that stabilize p53 in HPV-positive cancer cells
Authors: Martínez-Noël Gustavo , Szajner Patricia , Kramer Rebecca E. , Boyland Kathleen A. , Sheikh Asma , Smith Jennifer A. , Howley Peter M. 
Published: September 2020

AbstractEtiologically, 5% of all cancers worldwide are caused by the high-risk human papillomaviruses (hrHPVs). These viruses encode two oncoproteins (E6 and E7) whose expression is required for cancer initiation and maintenance. Among their cellular targets are the p53 and the retinoblastoma tumor suppressor proteins. Inhibition of the hrHPV E6-mediated ubiquitylation of p53 through the E6AP ubiquitin ligase results in the stabilization of p53, leading to cellular apoptosis. We utilized a live cell high throughput screen to determine whether exogenous microRNA (miRNA) transfection had the ability to stabilize p53 in hrHPV-positive cervical cancer cells expressing a p53-fluorescent protein as anin vivoreporter of p53 stability. Among the miRNAs whose transfection resulted in the greatest p53 stabilization was 375-3p that has previously been reported to stabilize p53 in HeLa cells, providing validation of the screen. The top 32 miRNAs in addition to 375-3p were further assessed using a second cell-based p53 stability reporter system as well as in non-reporter HeLa cells to examine their effects on endogenous p53 protein levels, resulting in the identification of 23 miRNAs whose transfection increased p53 levels in HeLa cells. While a few miRNAs that stabilized p53 led to decreases in E6AP protein levels, all targeted HPV oncoprotein expression. We further examined subsets of these miRNAs for their abilities to induce apoptosis and determined whether it was p53-mediated. The introduction of specific miRNAs revealed surprisingly heterogeneous responses in different cell lines. Nonetheless, some of the miRNAs described here have potential as therapeutics for treating HPV-positive cancers.ImportanceHuman papillomaviruses cause approximately 5% of all cancers worldwide and encode genes that contribute to both the initiation and maintenance of these cancers. The viral oncoprotein E6 is expressed in all HPV-positive cancers and functions by targeting the degradation of p53 through the engagement of the cellular ubiquitin ligase E6AP. Inhibiting the degradation of p53 leads to apoptosis in HPV-positive cancer cells. Using a high throughput live cell assay we identified several miRNAs whose transfection stabilize p53 in HPV-positive cells. These miRNAs have the potential to be used in the treatment of HPV-positive cancers.
Opportunities and challenges for improving a Colombian public research program in plant breeding and plant genetic resources lead by Agrosavia
Authors: Galeano Carlos H. , Tehelen Katherine , Jiménez Hugo R. , González Carolina , Cerón-Souza Ivania 
Published: September 2020

AbstractAgrosavia(Corporación Colombiana de Investigación Agropecuaria) is the Colombian state institution in charge of the agricultural research at the national level, including plant breeding. Since 2014, Agrosaviastarted to increase its research staff and has reset the leadership of public research to solve the needs of the agricultural sector population, focusing on small producers. However, the current team working on plant breeding and plant genetic resources are facing some challenges associated with generation gaps and the lack of a collaborative working plan for the next years. To identify the opportunities and actions in this research area, we surveyed all the 52 researchers working in Agrosaviain this area in 2017. We analyzed the opinions of researchers to detect the strengths and weaknesses of the program using a sentiment score. We also examined the networking to test both how consolidated the group is and if among top leaders are gender parity and also have a higher academic degree. Results showed that there is a mixed community of old and new researchers with clear gender bias in the proportion of male-female. Within the network, the interactions are weak, with several subgroups where the top-ten of both central leaders and the most influencer are frequently males with mostly an M.Sc. degree but with significant experience in the area. Researchers have an interest in 31 crops. From them, 26 are in the national germplasm bank, but this bank is not the primary source for their breeding programs. The top-five of plants with increasing interest are corn, cocoa tree, golden berries, oil palm, and sugarcane. Researchers also want to establish collaborations with 54 different institutions, where theUniversidad Nacional de Colombia, which is the top public university in the country, is on the head. Researchers also perceived weaknesses in the marker-assisted selection, experimental design, and participatory plant breeding, but those criticisms have a positive sentiment score average of 1.55 (0.3 SE) across 31 texts analyzed. Based on all results, we identified five critical strategic principles to improve the plant-breeding research program. They include a gender diversity policy to hire new researchers strategically to reduce the gender gap and strength the generational shift. Better collaboration between the national germplasm bank and plant breeding research. A coordinate plan where the studies focus on food security crops that the government supports independently of market trends. And finally, adequate spaces for the project’s design and training programs. Hence, we recommend the creation of a consultant group to implement these policies progressively in the next years.
Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19
Authors: Ma Jiahao , Su Danmei , Huang Xueqin , Liang Ying , Ma Yan , Liang Peng , Zheng Sanduo 
Published: September 2020

AbstractLess than a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 22 million people worldwide with a death toll approaching 1 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine.
Microplastic fibers affect dynamics and intensity of CO2and N2O fluxes from soil differently
Authors: Rillig Matthias C. , Hoffmann Mathias , Lehmann Anika , Liang Yun , Lück Matthias , Augustin Jürgen 
Published: September 2020

AbstractMicroplastics may affect soil ecosystem functioning in critical ways, with previously documented effects including changes in soil structure and water dynamics; this suggests that microbial populations and the processes they mediate could also be affected. Given the importance for global carbon and nitrogen cycle and greenhouse warming potential, we here experimentally examined potential effects of plastic microfiber additions on CO2and N2O greenhouse gas fluxes. We carried out a fully factorial laboratory experiment with the factors presence of microplastic fibers (0.4% w/w) and addition of urea fertilizer (100 mg N kg−1). The conditions in an intensively N-fertilized arable soil were simulated by adding biogas digestate at the beginning of the incubation to all samples. We continuously monitored CO2and N2O emissions from soil before and after urea application using a custom-built flow-through steady-state system, and we assessed soil properties, including soil structure. Microplastics affected soil properties, notably increasing soil aggregate water-stability and pneumatic conductivity, and caused changes in the dynamics and overall level of emission of both gases, but in opposite directions: overall fluxes of CO2were increased by microplastic presence, whereas N2O emission were decreased, a pattern that was intensified following urea addition. This divergent response is explained by effects of microplastic on soil structure, with the increased air permeability likely improving O2supply: this will have stimulated CO2production, since mineralization benefits from better aeration. Increased O2would at the same time have inhibited denitrification, a process contributing to N2O emissions, thus likely explaining the decrease in the latter. Our results clearly suggest that microplastic consequences for greenhouse gas emissions should become an integral part of future impact assessments, and that to understand such responses, soil structure should be assessed.