bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the Vaginal Flora Modify When a Synthetic Mesh is Used for Genital Prolapse Repair in Postmenopausal Women? A Pilot, Randomized Controlled Study
Authors: de Castro Edilson Benedito , Brito Luiz Gustavo Oliveria , Giraldo Paulo César , Teatin Juliato Cássia Raquel 
Published: January 2018

Objective
The vaginal flora from postmenopausal women with pelvic organ prolapse (POP) is different from younger women. We hypothesized that the decision of a surgical route using a mesh would modify the vaginal flora. The purpose of this study was to analyze the vaginal flora from postmenopausal women that were submitted to abdominal sacrocervicopexy or vaginal sacrospinous fixation.

Methods
A pilot, randomized controlled study with 50 women aged 55 to 75 years (n = 25; abdominal sacrocervicopexy + subtotal hysterectomy; n = 25 vaginal sacrospinous fixation + vaginal hysterectomy) was performed. A polyvinylidene mesh was used in both arms. The vaginal content analysis was collected before and 60 days after the surgery. The type of flora, the presence of lactobacilli/leukocytes, and the Nugent criteria were analyzed.

Results
Most of the women were white (80%), with at least 1 comorbidity (69.9%), did not present sexual activity (60%), and presented advanced stage 4 POP. Two thirds of women presented a type 3 flora, and half of them did not present lactobacilli (48.3%). About the Nugent criteria, 51.7% presented normal flora, 46.6% found altered flora, and 1.7% had bacterial vaginosis. There were no differences about the type of flora (P = 1), number of lactobacilli (P = 0.9187), Nugent criteria (P = 0.4235), inflammation (P = 0.1018), and bacterial vaginosis (P = 0.64) before and after surgery in both groups.

Conclusions
In this pilot study, the use of synthetic mesh by vaginal or abdominal route did not affect the vaginal flora in postmenopausal women operated on by POP surgery.
Wolbachia control stem cell behavior and stimulate germline proliferation in filarial nematodes
Authors: Vincent Foray , M. Pérez-Jiménez Mercedes , Nour Fattouh , Frédéric Landmann 
Published: January 2018

SUMMARYAlthough symbiotic interactions are ubiquitous in the living world, examples of developmental symbioses are still scarce. We show here the crucial role of Wolbachia in the oogenesis of filarial nematodes, a class of parasites of biomedical and veterinary relevance. While the Wolbachia-depleted nematodes produce faulty embryos, we identified thanks to newly generated techniques the earliest requirements of Wolbachia in the germline. They stimulate its proliferation in a cell-autonomous manner, in parallel of the known key controllers, and not through nucleotide supplementation as previously hypothesized. We also found Wolbachia to maintain the quiescence of a pool of germline stem cells ensuring for many years a constant delivery of about 1400 eggs per day. The loss of quiescence upon Wolbachia depletion, as well as the disorganization of the distal germline suggest that Wolbachia are required to execute the proper germline stem cell developmental program in order to produce viable eggs and embryos.
Prokaryotic nanocompartments form synthetic organelles in a eukaryote
Authors: Lau Yu Heng , Giessen Tobias W. , Altenburg Wiggert J. , Silver Pamela A. 
Published: January 2018

AbstractCompartmentalization of proteins into organelles is a promising strategy for enhancing the productivity of engineered eukaryotic organisms. However, approaches that co-opt endogenous organelles may be limited by the potential for unwanted crosstalk and disruption of native metabolic functions. Here, we present the construction of synthetic non-endogenous organelles in the eukaryotic yeast Saccharomyces cerevisiae, based on the prokaryotic family of self-assembling proteins known as encapsulins. We establish that encapsulins self-assemble to form nanoscale compartments in yeast, and that heterologous proteins can be selectively targeted for compartmentalization. Housing destabilized proteins within encapsulin compartments affords protection against proteolytic degradation in vivo, while the interaction between split protein components is enhanced upon co-localization within the compartment interior. Furthermore, encapsulin compartments can support enzymatic catalysis, with substrate turnover observed for an encapsulated yeast enzyme. Encapsulin compartments therefore represent a modular platform, orthogonal to existing organelles, for programming synthetic compartmentalization in eukaryotes.
Evolutionary tradeoffs and the structure of allelic polymorphisms
Authors: Sheftel Hila , Szekely Pablo , Mayo Avi , Sella Guy , Alon Uri 
Published: January 2018

AbstractPopulations of organisms show prevalent genetic differences called polymorphisms. Understanding the effects of polymorphisms is of central importance in biology and medicine. Here, we ask which polymorphisms occur at high frequency when organisms evolve under tradeoffs between multiple tasks. Multiple tasks present a problem, because it is not possible to be optimal at all tasks simultaneously and hence compromises are necessary. Recent work indicates that tradeoffs lead to a simple geometry of phenotypes in the space of traits: phenotypes fall on the Pareto front, which is shaped as a polytope: a line, triangle, tetrahedron etc. The vertices of these polytopes are the optimal phenotypes for a single task. Up to now, work on this Pareto approach has not considered its genetic underpinnings. Here, we address this by asking how the polymorphism structure of a population is affected by evolution under tradeoffs. We simulate a multi-task selection scenario, in which the population evolves to the Pareto front: the line segment between two archetypes or the triangle between three archetypes. We find that polymorphisms that become prevalent in the population have pleiotropic phenotypic effects that align with the Pareto front. Similarly, epistatic effects between prevalent polymorphisms are parallel to the front. Alignment with the front occurs also for asexual mating. Alignment is reduced when drift or linkage is strong, and is replaced by a more complex structure in which many perpendicular allele effects cancel out. Aligned polymorphism structure allows mating to produce offspring that stand a good chance of being optimal multi-taskers in at least one of the locales available to the species.
Neuraminidase inhibitors — is it time to call it a day?
Authors: Parra-Rojas César , Nguyen Van Kinh , Hernández-Mejía Gustavo , Hernández-Vargas Esteban A. 
Published: January 2018

AbstractStockpiling neuraminidase inhibitors (NAIs) such as oseltamivir and zanamivir is part of a global effort to be prepared for an influenza pandemic. However, the contribution of NAIs for treatment and prevention of influenza and its complications is largely debatable. Here, we developed a transparent mathematical modelling setting to analyse the impact of NAIs on influenza disease at within-host and population level. Analytical and simulation results indicate that even assuming unrealistically high efficacies for NAIs, drug intake starting on the onset of symptoms has a negligible effect on an individual's viral load and symptoms score. Increasing NAIs doses does not provide a better outcome as is generally believed. Considering Tamiflu's pandemic regimen for prophylaxis, different multiscale simulation scenarios reveal modest reductions in epidemic size despite high investments in stockpiling. Our results question the use of NAIs in general to treat influenza as well as the respective stockpiling by regulatory authorities.
BRD4 Deficiency Selectively Affects a Unique Developmental Subpopulation in Thymocytes
Authors: Gegonne Anne , Chen Qing-Rong , Dey Anup , Etzensperger Ruth , Tai Xuguang , Singer Alfred , Meerzaman Daoud , Ozato Keiko , Singer Dinah S. 
Published: January 2018

ABSTRACTThe bromodomain protein BRD4 is a driver in both inflammatory diseases and cancers. It has multiple functions, contributing to chromatin structure and transcription through its intrinsic HAT and kinase activities. Despite the wide-ranging characterization of BRD4, little is known about its in vivo function. In the present study, we have examined the role of BRD4 in T cell development by conditional deletion at various stages of thymocyte differentiation. We found that BRD4 is critical for normal T cell development. Surprisingly, BRD4 selectively regulates the progression of immature CD8 single positive (ISP) thymocytes into quiescent DP thymocytes. In striking contrast, BRD4 deletion does not affect the extensive proliferation associated with the differentiation of double negative (DN) into ISP cells. Nor does it affect the maturation of double positive (DP) into conventional CD4+ and CD8+ thymocytes. These studies lead to the unexpected conclusion that BRD4 selectively regulates preselection ISP thymocytes.On-line SummaryImmature CD8 single-positive (ISP) thymocytes are identified as a molecularly-distinct thymocyte subpopulation, dependent on BRD4 for progression to the DP stage. DN and DP are BRD4-independent. These findings provide new insights into BRD4, a therapeutic target in inflammation and cancer.
Differential 3’ Processing of Specific Transcripts Expands Regulatory and Protein Diversity Across Neuronal Cell Types
Authors: Jereb Saša , Hwang Hun-Way , Van Otterloo Eric , Govek Eve-Ellen , Fak John J. , Yuan Yuan , Hatten Mary E. , Darnell Robert B. 
Published: January 2018

ABSTRACTAlternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3’UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3’UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3’UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies.
Arabidopsis HB52 mediates the crosstalk between ethylene and auxin signaling pathways by regulatingPIN2, WAG1, and WAG2during primary root elongation
Authors: Miao Zi-Qing , Zhao Ping-Xia , Mao Jie-Li , Yu Lin-Hui , Yuan Yang , Tang Hui , Xiang Cheng-Bin 
Published: January 2018

AbstractThe gaseous hormone ethylene participates in many physiological processes of plants. It is well known that ethylene-inhibited root elongation involves basipetal auxin delivery requiring PIN2. However, the molecular mechanism how ethylene regulatesPIN2is not well understood. Here, we report that the ethylene-responsive HD-Zip geneHB52is involved in ethylene-mediated inhibition of primary root elongation. Using biochemical and genetic analyses, we demonstrated thatHB52is ethylene-responsive and acts immediately downstream of EIN3.HB52knock-down mutants are insensitive to ethylene in primary root elongation while the overexpression lines have dramatically shortened roots like ethylene treated plants. Moreover, HB52 upregulatesPIN2, WAG1, andWAG2by directly binding to their promoter, leading to an enhanced basipetal auxin delivery to the elongation zone and thus inhibiting root growth. Our work uncovers HB52 as an important crosstalk node between ethylene signaling and auxin transport in root elongation.
Data-mining of Antibiotic Resistance Genes Provides Insight into the Community Structure of Ocean Microbiome
Authors: Hao Shiguang , Yang Pengshuo , Han Maozhen , Xu Junjie , Yu Shaojun , Chen Chaoyun , Chen Wei-Hua , Zhang Houjin , Ning Kang 
Published: January 2018

AbstractBackgroundAntibiotics have been spread widely in environments, asserting profound effects on environmental microbes as well as antibiotic resistance genes (ARGs) within these microbes. Therefore, investigating the associations between ARGs and bacterial communities become an important issue for environment protection. Ocean microbiomes are potentially large ARG reservoirs, but the marine ARG distribution and its associations with bacterial communities remain unclear.Methodswe have utilized the big-data mining techniques on ocean microbiome data to analysis the marine ARGs and bacterial distribution on a global scale, and applied comprehensive statistical analysis to unveil the associations between ARG contents, ocean microbial community structures, and environmental factors by reanalyzing 132 metagenomic samples from the Tara Oceans project.ResultsWe identified in total 1,926 unique ARGs and found that: firstly, ARGs are more abundant and diverse in the mesopelagic zone than other water layers. Additionally, ARG-enriched genera are closely connected in co-occurrence network. We also found that ARG-enriched genera are often more abundant than their ARG-less neighbors. Furthermore, we found that samples from the Mediterranean that is surrounded by human activities often contain more ARGs.ConclusionOur research for investigating the marine ARG distribution and revealing the association between ARG and bacterial communities provide a deeper insight into the marine bacterial communities. We found that ARG-enriched genera were often more abundant than their ARG-less neighbors in the same environment, indicating that genera enriched with ARGs might possess an advantage over others in the competition for survival in the oceanic microbial communities.
Noise propagation in an integrated model of bacterial gene expression and growth
Authors: Kleijn Istvan T. , Krah Laurens H. J. , Hermsen Rutger 
Published: January 2018

AbstractIn bacterial cells, gene expression, metabolism, and growth are highly interdependent and tightly coordinated. As a result, stochastic fluctuations in expression levels and instantaneous growth rate show intricate cross-correlations. These correlations are shaped by feedback loops, trade-offs and constraints acting at the cellular level; therefore a quantitative understanding requires an integrated approach. To that end, we here present a mathematical model describing a cell that contains multiple proteins that are each expressed stochastically and jointly limit the growth rate. Conversely, metabolism and growth affect protein synthesis and dilution. Thus, expression noise originating in one gene propagates to metabolism, growth, and the expression of all other genes. Nevertheless, under a small-noise approximation many statistical quantities can be calculated analytically. We identify several routes of noise propagation, illustrate their origins and scaling, and establish important connections between noise propagation and the field of metabolic control analysis. We then present a many-protein model containing > 1000 proteins parameterized by previously measured abundance data and demonstrate that the predicted cross-correlations between gene expression and growth rate are in broad agreement with published measurements.
Src-transformed cells hijack mitosis to extrude from the epithelium
Authors: Anton Katarzyna A. , Kajita Mihoko , Narumi Rika , Fujita Yasuyuki , Tada Masazumi 
Published: January 2018

AbstractAt the initial stage of carcinogenesis single mutated cells appear within an epithelium. Mammalianin vitroexperiments show that potentially cancerous cells undergo live apical extrusion from normal monolayers. However, the mechanism underlying this processin vivoremains poorly understood. Mosaic expression of the oncogene vSrc in a simple epithelium of the early zebrafish embryo results in apical extrusion of transformed cells. Here we find that during extrusion components of the cytokinetic ring are recruited to adherens junctions of transformed cells, stimulating formation of a misoriented pseudo cytokinetic ring. During extrusion, the ring constricts and separates the basal from the apical part of the cell releasing both from the epithelium. This process requires cell cycle progression and occurs immediately after vSrc-transformed cell enters mitosis. To achieve extrusion, vSrc coordinates cell cycle progression, junctional integrity, cell survival and apicobasal polarity. Without vSrc, modulating these cellular processes reconstitutes vSrc-like extrusion, confirming their sufficiency for this process.
Successive Bloodmeals Enhance Virus Dissemination Within Mosquitoes And Increase Transmission Potential
Authors: Armstrong Philip M. , Ehrlich Hanna , Bransfield Angela , Warren Joshua L. , Pitzer Virginia E. , Brackney Doug E. 
Published: January 2018

SUMMARY PARAGRAPHThe recent Zika virus (ZIKV) and chikungunya virus (CHIKV) epidemics highlight the explosive nature of arthropod-borne (arbo) viruses transmitted by Aedes aegypti mosquitoes1,2. Vector competence and the extrinsic incubation period (EIP) are two key entomological parameters used to assess the public health risk posed by arboviruses3. These are typically measured empirically by offering mosquitoes an infectious bloodmeal and temporally sampling mosquitoes to determine infection and transmission status. This approach has been used for the better part of a century; however, it does not accurately capture the biology and behavior of many mosquito vectors which refeed frequently (every 2-3 days)4. Here we demonstrate that administration of a second non-infectious bloodmeal significantly shortens the EIP of ZIKV-infected Ae. aegypti by enhancing virus escape from the mosquito midgut. Similarly, a second bloodmeal increased the competence of this species for dengue virus and CHIKV. This effect was also observed for ZIKV in Aedes albopictus, suggesting that this species might be a more important vector than once thought and that this phenomenon may be common among other virus-vector pairings. Modeling of these findings reveals that a shortened EIP would result in a significant increase in the basic reproductive number, R0. This increase helps explain how Ae.aegypti can sustain an explosive epidemic like ZIKV despite its relatively poor vector competence in single-feed laboratory trials. Together, these data demonstrate a direct and unrecognized link between mosquito feeding behavior, EIP, and vector competence.
A Transcriptomic Analysis of Xylan Mutants Does Not Support the Existence of A Secondary Cell Wall Integrity System in Arabidopsis
Authors: Blanc Nuno Faria , Mortimer Jenny C. , Dupree Paul 
Published: January 2018

AbstractYeast have long been known to possess a cell wall integrity (CWI) system, and recently an analogous system has been described for the primary walls of plants (PCWI) that leads to changes in plant growth and cell wall composition. A similar system has been proposed to exist for secondary cell walls (SCWI). However, there is little data to support this. Here, we analysed the stem transcriptome of a set of cell wall biosynthetic mutants in order to investigate whether cell wall damage, in this case caused by aberrant xylan synthesis, activates a signalling cascade or changes in cell wall synthesis gene expression. Our data revealed remarkably few changes to the transcriptome. We hypothesise that this is because cells undergoing secondary cell wall thickening have entered a committed programme leading to cell death, and therefore a SCWI system would have limited impact. The absence of transcriptomic responses to secondary cell wall alterations may facilitate engineering of the secondary cell wall of plants.
Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism
Authors: Kim Huen Suk , Yoo Seungyeul , Bernitz Jeffrey M. , Yuan Ye , Gomes Andreia M. , Daniel Michael G. , Su Jie , Demicco Elizabeth G. , Zhu Jun , Moore Kateri A. , Lee Dung-Fang , Lemischka Ihor R. , Schaniel Christoph 
Published: January 2018

AbstractOsteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigated an oncogenic role of secreted frizzled-related protein 2 (sFRP2) in P53 mutation-associated OS development. Interestingly, we found that high sFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of sFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic sFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin independent manner. Conversely, inhibition of sFRP2, FOXM1 or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of sFRP2 in P53 mutation-associated OS development and that inhibition of sFRP2 is a potential therapeutic strategy.
A conceptual model of social entrepreneurial intention based on the social cognitive career theory
Authors: Tran Anh T.P. , Von Korflesch Harald 
Published: January 2018

PurposeEntrepreneurial intention plays a major role in entrepreneurship academia and practice. However, little is known about the intentions of entrepreneurs in the social area of venture creation. This paper aims to formulate a well-organized model of social entrepreneurial intention.Design/methodology/approachThe paper draws on intention models in entrepreneurship literature in general and social entrepreneurship in particular to identify gaps. Based on these findings, a new conceptual model is formulated.FindingsThere is no research to be found which uses the social cognitive career theory (SCCT) to explain about an individual’s intention to become a social entrepreneur, although this theory is recently suggested as an inclusive framework for entrepreneurial intention (Doan Winkelet al., 2011). It is also supportive by the empirical research of Segalet al.(2002). Therefore, a conceptual model of entrepreneurial intention in the field of social entrepreneurship is formulated based on adapting and extending the SCCT.Originality/valueThe paper contributes to the social entrepreneurship literature by providing new insights about social entrepreneurial intention. The result has important implications for theory and practice. In theory, it is the first model offering the SCCT as the background of formation for social entrepreneurial intention, with a distinct perspective of social entrepreneurship as a career. It raises a future direction for researchers to test this model. In practice, this framework provides a broad view of factors that could contribute to the success of the would-be a social entrepreneur.