bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to death and its Predictors among Adult TB/HIV Co-Infected Patients in Mizan Tepi University Teaching Hospital, South West Ethiopia
Authors: Wondimu Wondimagegn , Dube Lamessa , Kabeta Teshome 
Published: August 2019

AbstractBackgroundTuberculosis (TB) and Human Immuno Deficiency Virus (HIV) co-infection represents a complex pathogenic scenario with synergistic effect and leads to about 300,000 HIV-associated TB deaths in the world in 2017. Despite this burden of death, time to death and its predictors among TB-HIV co-infected patient was not adequately studied; and the existing evidences are inconsistent. Therefore, this study was aimed to determine time to death and identify its predictors among adult TB/HIV co-infected patients.MethodRetrospective cohort study was conducted by reviewing registers of randomly selected 364 TB/HIV co-infected patients enrolled in health care from July 2, 2007 up to July 1, 2017 at Mizan Tepi University Teaching Hospital. The hospital was located in Bench Maji Zone, South West Ethiopia. Data were collected from March 1 through 31, 2018, entered to Epi data 3.1 and exported to SPSS version 21. Each patient was followed from date of TB treatment initiation till death, loss to follow up and treatment completed. On the other hand, events other than death were considered as censored. After checking the proportional hazard model assumption, Cox-regression was used to identify the predictors. In bivariable analyses, P-value≤0.25 was used to identify candidate variables for multivariable analysis. The 95% CI of hazard ratio (HR) with respective P-value <0.05 was used to declare significance in the final model.ResultAll the 364 patients were followed for 1,654 person months. There were 83 (22.8%) deaths and most 38 (45.8%) were occurring within the first two months of anti-TB treatment initiation. The overall incidence rate and median survival time were 5.02 per 100 person months (95% CI: 4.05, 6.22) and 10 months respectively. Statistically significant better survival was observed among patients: with CD4 ≥ 200 cells/mm3 (P<0.001), who had a history of cotrimoxazole preventive therapy (CPT) use (P<0.001), who disclose their HIV status (P<0.001) and with working functional status (P<0.001). Not using CPT (adjusted hazard ratio [AHR] =1.72; P=0.023), bedridden functional status (AHR=2.55; P=0.007), not disclosing HIV status (AHR=4.03; P<0.001) and CD4 < 200 cells/mm3 (AHR=6.05; P<0.001) were predictors of time to death among TB/HIV co-infected patients.ConclusionThe median survival time was 10 months and poor survival was associated with low CD4 count, not using CPT, not disclosing HIV status and having bedridden functional status. Close monitoring of bedridden and low CD4 count patients, prompt CPT initiation and encouraging HIV status disclosure are recommended.
Recapitulation and reversal of schizophrenia-related phenotypes in Setd1a-deficient mice
Authors: Mukai Jun , Cannavò Enrico , Sun Ziyi , Crabtree Gregg , Diamantopoulou Anastasia , Thakur Pratibha , Chang Chia-Yuan , Cai Yifei , Lomvardas Stavros , Takata Atsushi , Xu Bin , Gogos Joseph A. 
Published: August 2019

SummarySETD1A, a histone methyltransferase, is a key schizophrenia susceptibility gene. Mutant mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics, accompanied by specific deficits in working memory that recapitulates SCZ-related alterations. We show that Setd1a targets mostly enhancers and reveal a striking overlap between Setd1a and Mef2 chromatin targets. Setd1a targets are highly expressed in pyramidal neurons and enriched for genes with postnatally-biased expression involved in synaptic structure and function. Notably, evolutionary conserved Setd1a binding sites and target genes are strongly associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues working memory deficits. We identify LSD1 as a major demethylase counteracting the effects of Setd1a methyl transferase activity and show that LSD1 antagonism in adult Setd1a-deficient mice results in a full rescue of the behavioral abnormalities and axonal branching deficits. Our findings advance our understanding of how SETD1A mutations predispose to SCZ and point to therapeutic interventions.
Mining the human tonsillar microbiota as autoimmune modulator
Authors: Li Jing , Li Shenghui , Jin Jiayang , Guo Ruochun , Sun Xiaolin , Guo Jianping , Hu Fanlei , Liu Yanying , Jin Yuebo , Zhou Yunshan , Xiao Wenjing , Zhong Yan , Huang Fei , Pan Hudan , Yang Rentao , Zhou Yuanjie , Deng Kaifeng , Wu Lijun , Liu Liang , Qin Junjie , Wang Jun , He Jing , Li Zhanguo 
Published: August 2019

AbstractPalatine tonsils are important lymphoid organs featuring constant cross-talks between the commensal microorganisms and immune system, and have been implicated as critical autoimmunity origins for immune-related diseases, including rheumatoid arthritis (RA), a common autoimmune disorder. However, there was no evidence to show link between tonsillar microbiota and RA. Here, we identified a significant dysbiosis of RA tonsillar microbiota, with loss of Streptococcus salivarius and its functional molecules salivaricins (a type of antibacterial peptides). Consistent with the niche-preference, S. salivarius and salivaricins administrated intranasally or intraorally conferred prophylactic and therapeutic efficacies against experimental arthritis. Moreover, we demonstrated, for the first time, that S. salivarius and salivaricins exerted immunosuppressive capacities via inhibiting CD4+effector T cell subsets and autoantibody production in mice and human. These results uncover a communication between tonsillar microbiota and host autoimmunity, and identify the active components from tonsillar microbes in modulating immune homeostasis.One sentence summaryTonsillar microbiota regulate host autoimmunity via antibacterial peptides
Case studies and mathematical models of ecological speciation. V. Adaptive divergence of whitefish in Fennoscandia
Authors: Thibert-Plante Xavier , Præbel Kim , Østbye Kjartan , Kahilainen Kimmo K. , Amundsen Per-Arne , Gavrilets Sergey 
Published: August 2019

AbstractModern speciation theory has greatly benefited from a variety of simple mathematical models focusing on the conditions and patterns of speciation and diversification in the presence of gene flow. Unfortunately the application of general theoretical concepts and tools to specific ecological systems remains a challenge. Here we apply modeling tools to better understand adaptive divergence of whitefish during the postglacial period in lakes of northern Fennoscandia. These lakes harbor up to three different morphs associated with the three major lake habitats: littoral, pelagic, and profundal. Using large-scale individual-based simulations, we aim to identify factors required for in situ emergence of the pelagic and profundal morphs in lakes initially colonized by the littoral morph. The importance of some of the factors we identify and study - sufficiently large levels of initial genetic variation, size- and habitat-specific mating, sufficiently large carrying capacity of the new niche - is already well recognized. In addition, our model also points to two other factors that have been largely disregarded in theoretical studies: fitness-dependent dispersal and strong predator pressure in the ancestral niche coupled with the lack of it in the new niche(s). We use our theoretical results to speculate about the process of diversification of whitefish in Fennoscandia and to identify potentially profitable directions for future empirical research.
PulmonDB: a curated lung disease gene expression database
Authors: Villaseñor-Altamirano Ana B. , Moretto Marco , Zayas-Del Moral Alejandra , Maldonado Mariel , Munguía-Reyes Adrián , Romero Yair , García-Sotelo Jair. S. , Aguilar Luis Alberto , Oscar Aldana-Assad , Engelen Kristof , Selman Moisés , Collado-Vides Julio , Balderas-Martínez Yalbi I. , Medina-Rivera Alejandra 
Published: August 2019

ABSTRACTChronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) have contrasting clinical and pathological characteristics, and interesting whole-genome transcriptomic profiles. However, data from public repositories are difficult to reprocess and reanalyze. Here we present PulmonDB, a web-based database (http://pulmondb.liigh.unam.mx/) and R library that facilitates exploration of gene expression profiles for these diseases by integrating transcriptomic data and curated annotation from different sources. We demonstrated the value of this resource by presenting the expression of already well-known genes of COPD and IPF across multiple experiments and the results of two differential expression analyses in which we successfully identified differences and similarities. With this first version of PulmonDB, we create a new hypothesis and compare the two diseases from a transcriptomics perspective.
Post-translational control of PlsB is sufficient to coordinate membrane synthesis with growth inEscherichia coli
Authors: Noga Marek J , Büke Ferhat , van den Broek Niels JF , Imholz Nicole , Scherer Nicole , Yang Flora , Bokinsky Gregory 
Published: August 2019

AbstractEvery cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways ofEscherichia coliacross a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyses the committed step of lipopolysaccharide synthesis (LpxC) do not vary across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we find that responses to environmental perturbations are triggered directly via changes in acetyl-CoA concentrations, which enables rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon post-translational regulation ensures both reliability and responsiveness of membrane synthesis.SignificanceHow do bacteria cells grow without breaking their membranes? Although the biochemistry of fatty acid and membrane synthesis is well-known, how membrane synthesis is balanced with growth and metabolism has remained unclear. This is partly due to the many control points that have been discovered within the membrane synthesis pathways. By precisely establishing the contributions of individual pathway enzymes, our results simplify the model of membrane biogenesis in the model bacteria speciesEscherichia coli. Specifically, we find that allosteric control of a single enzyme, PlsB, is sufficient to balance growth with membrane synthesis and to ensure that growingE. coliproduces sufficient membrane. Identifying the signals that activate and deactivate PlsB will answer the question of how membrane synthesis is synchronized with growth.
Emergence and patterning dynamics of mouse definitive endoderm
Authors: Pour Maayan , Kumar Abhishek Sampath , Walther Maria , Wittler Lars , Meissner Alexander , Nachman Iftach 
Published: August 2019

AbstractThe segregation of definitive endoderm (DE) from mesendoderm progenitors leads to the formation of two distinct germ layers. Dissecting DE onset has been challenging as it occurs within a narrow spatio-temporal window in the embryo. Here we employ a dual Bra-GFP, Sox17-RFP reporter cell line to study DE onset dynamics. We find Sox17 starts in a few isolated cellsin vivo. Using 2D and 3Din vitromodels, we show that DE cells emerge from mesendoderm progenitors at a temporally regular, but spatially stochastic pattern, which is subsequently arranged by self-sorting of Sox17+ cells. Self-sorting coincides with up-regulation of E-cadherin but is not necessary for DE differentiation or proliferation. A subpopulation of Bra-high cells commits to a Sox17+ fate independent of external Wnt signal. Ourin vivoandin vitroresults highlight basic rules governing DE onset and patterning through the commonalities and differences between these systems.
Emergence and diversification of a host-parasite RNA ecosystem through Darwinian evolution
Authors: Furubayashi Taro , Ueda Kensuke , Bansho Yohsuke , Motooka Daisuke , Nakamura Shota , Ichihashi Norikazu 
Published: August 2019

AbstractIn the prebiotic evolution, molecular self-replicators are considered to develop into diverse, complex living organisms. The appearance of parasitic replicators is believed inevitable in this process. However, the role of parasitic replicators on prebiotic evolution remains elusive. Here, we demonstrated experimental coevolution of RNA self-replicators (host RNAs) and emerging parasitic replicators (parasitic RNAs) for the first time by using an RNA-protein replication system we had developed. During a long-term replication experiment, a clonal population of the host RNA turned into an evolving host-parasite ecosystem through the continuous emergence of new types of host and parasitic RNAs produced by replication errors. The diversified host and parasitic RNAs exhibited evolutionary arms-race dynamics. The parasitic RNA accumulated unique mutations that the host RNA had never acquired, thus adding a new genetic variation to the whole replicator ensemble. These results provide the first experimental evidence that the coevolutionary interplay between host-parasite molecules play a key role in generating diversity and complexity in prebiotic molecular evolution.
Helicobacter pylori biofilm cells are metabolically distinct, express flagella, and antibiotic tolerant
Authors: Hathroubi Skander , Zerebinski Julia , Ottemann Karen M. 
Published: August 2019

ABSTRACTBiofilm growth protects bacteria against harsh environments, antimicrobials, and immune responses. Helicobacter pylori is a bacterium that has a robust ability to maintain colonization in a challenging environment. Over the last decade, H. pylori biofilm formation has begun to be characterized, however, there are still gaps in our understanding about how this growth mode is defined and its impact on H. pylori physiology. To provide insights into H. pylori biofilm growth properties, we characterized the antibiotic susceptibility, gene expression, and genes required for biofilm formation of a strong biofilm-producing H. pylori. H. pylori biofilms developed complex 3D structures and were recalcitrant to multiple antibiotics. Disruption of the protein-based matrix decreased this antibiotic tolerance. Using both transcriptomic and genomic approaches, we discovered that biofilm cells demonstrated lower transcripts for TCA cycle enzymes but higher ones for hydrogenase and acetone metabolism. Interestingly, several genes encoding for the natural competence Type IV secretion system 4 (tfs4) were up-regulated during biofilm formation along with several genes encoding for restriction-modification (R-M) systems, suggesting DNA exchange activities in this mode of growth. Flagella genes were also discovered through both approaches, consistent with previous reports about the importance of these filaments in H. pylori biofilm. Together, these data suggest that H. pylori is capable of adjusting its phenotype when grown as biofilm, changing its metabolism and elevating specific surface proteins including those encoding tfs4 and flagella.
Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos
Authors: Koca Yildiz , Housden Benjamin E. , Gault William J. , Bray Sarah J. , Mlodzik Marek 
Published: August 2019

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. InDrosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles ofNotch– belonging to theNfacetclass – reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated morphogenetic cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription ofargos (aos), an inhibitory ligand to the EGFR, to fine-tune the activity of Egfr signaling. Consistently, the loss-of-function defects ofNfacetalleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulatedaosenhancer confers R4 specific expression arguing thataosis directly regulated by Notch signaling in this context via Su(H)- Mam dependent transcription.
Cas12a-based on-site and rapid nucleic acid detection of African swine fever
Authors: Bai Jing , Lin Haosi , Li Haojian , Zhou Yang , Liu Junshan , Zhong Guorui , Wu Luting , Jiang Weifan , Du Hongli , Yang Jinyi , Xie Qingmei , Huang Lizhen 
Published: August 2019

AbstractThe mortality rate of hemorrhagic African swine fever (ASF), which targets domestic pigs and is caused by African swine fever virus (ASFV), can reach 100%. ASF has been reported in 25 Chinese provinces since August 2018. There is no effective treatment or vaccine for it and the present molecular diagnosis technologies have trade-offs in sensitivity, specificity, cost and speed, and none of them cater perfectly to ASF control. Thus, a technology that overcomes the need for laboratory facilities, is relatively low cost, and rapidly and sensitively detects ASFV would be highly valuable. Here, we describe an RAA-Cas12a-based system that combines recombinase-aided amplification (RAA) and CRISPR/Cas12a for ASFV detection. The fluorescence intensity readout of this system detected ASFV p72 gene levels as low as 10 aM. For on-site ASFV detection, lateral-flow strip readout was introduced for the first time in the RAA-Cas12a based system (named CORDS, Cas12a-based On-site and Rapid Detection System). We used CORDS to detect target DNA highly specifically using the lateral-flow strip readout. CORDS could identify the p72 gene at femtomolar sensitivity in an hour at 37°C, and only requires an incubator. For ease of use, the regents of CORDS was lyophilized to three tubes and remained the same sensitivity when stored at 4 °C for at least 7 days. Thus, CORDS provides a rapid, sensitive and easily operable method for ASFV on-site detection. Lyophilized CORDS can withstand long-term transportation and storage, and is ready for field applications.
Relationship between birth weight and chronic kidney disease: an integrative analysis of observational studies and causal inference through genetic approaches
Authors: Yu Xinghao , Yuan Zhongshang , Chen Haimiao , Yang Jiaji , Gao Yixin , Guan Fengjun , Zeng Ping , Huang Shuiping 
Published: August 2019

ABSTRACTObjectiveAlthough many observational studies have shown that there was an inverse association between birth weight and chronic kidney disease (CKD) in adults, whether such association is causal remains largely unclear.MethodsWe first conducted a systematic review and meta-analysis to investigate the association between birth weight and CKD. Then using a set of valid instrumental variables for birth weight, we performed a two-sample Mendelian randomization (MR) to evaluate its causal effect on CKD based on summary association statistics available from large scale genome-wide association study (GWAS) (up to 143,677 individuals for birth weight and 118,147 individuals for CKD). We further validated the MR results with extensive sensitive analyses.ResultsThe results of meta-analysis showed that individuals with low birth weight have about 76% (95% CI 36∼126%) higher risk of CKD in late life compared with those with normal birth weight. Depending on 26 instrumental variables, the inverse variance weighted MR showed that the odds ratio per one SD increase of birth weight on CKD was estimated to be 0.91 (95% CI 0.72∼1.14, p=0.396). The similar null association between birth weight and CKD is also observed using the weighted median method and maximum likelihood method as well as the Egger regression. Such non-significant association is robust against potential instrumental outliers and pleiotropic effects.ConclusionOur study identifies an inverse association between birth weight and adult CKD in observational studies, while it is not supportive of the causal role of birth weight on CKD based on our MR analysis.
A novel stibium phosphate, LiBa(SbO)2(PO4)3: synthesis, crystal structure and RE3+-activated (RE = Tb3+ and Eu3+) fluorescence performance
Authors: Zhang Shi-Rui , Zhao Dan , Zhang Rui-Juan , Shi Lin-Ying , Dai Shao-Jie , Fan Yun-Chang 
Published: August 2019

A new stibium phosphate, lithium barium bis(antimony oxide) tris(phosphate), LiBa(SbO)2(PO4)3, was prepared by the molten salt method with LiF as the flux. The crystal structure consists of an original three-dimensional anionic framework of [(SbO)2(PO4)3]∞ built from PO4 tetrahedra sharing their corners with SbO6 octahedra. This framework delimits one-dimensional tunnels where the lithium(I) and barium(II) ions are located. The UV–Vis spectrum shows that LiBa(SbO)2(PO4)3 was transparent from 350 to 800 nm, and is thus suitable as a luminescent host matrix. We then used Tb3+ and Eu3+ activators to test its luminous performance and the purities of the prepared phosphors were studied by powder X-ray diffraction analysis with Rietveld refinements. Photoluminescence (PL) studies reveal that the emission spectra of 1 mol% RE3+-doped (RE = Tb and Eu) samples can be excited by 371 and 394 nm light, emitting green and orange–red light, respectively, for Tb3+ and Eu3+. The CIE coordinates were measured to be (0.295, 0.571) and (0.6027, 0.3967), and the luminescent lifetimes were calculated as 0.178 and 1.159 ms, respectively.