bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-free biogenesis of bacterial division proto-rings that can constrict liposomes
Authors: Godino Elisa , López Jonás Noguera , Zarguit Ilias , Doerr Anne , Jimenez Mercedes , Rivas Germán , Danelon Christophe 
Published: March 2020

ABSTRACTA major challenge towards the realization of an autonomous synthetic cell resides in the encoding of a division machinery in a genetic programme. A key event in the bacterial cell cycle is the assembly of cytoskeletal proteins into a ring that defines the division site. At the onset of the formation of theEscherichia colidivisome, a proto-ring consisting of FtsZ and its membrane recruiting proteins takes place. Here, we show that FtsA-FtsZ ring-like structures driven by cell-free gene expression can be reconstituted on planar membranes and inside liposome compartments. Such cytoskeletal structures are found to constrict the membrane and generate budding vesicles, a phenotype that has not been reported before. Additional expression of the FtsZ cross-linker protein ZapA yields more rigid FtsZ bundles that attach to the membrane but fail to produce budding spots or necks in liposomes. These results provide new insights on the self-organization of basic cytoskeletal elements involved in bacterial division. Moreover, they demonstrate that gene-directed protein synthesis and assembly of membrane-constricting FtsZ-rings can be combined in a liposome-based artificial cell.
NAD+prevents septic shock-induced death by non-canonical inflammasome blockade and IL-10 cytokine production in macrophages
Authors: Iske Jasper , El Fatimy Rachid , Nian Yeqi , Ghouzlani Amina , Eskandari Siawosh K. , Cetina Biefer Hector Rodriguez , Vasudevan Anju , Elkhal Abdallah 
Published: March 2020

AbstractSeptic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and pro-inflammatory cytokine production via caspase-11 and Gasdermin-D (GSDMD). Here, we show that NAD+treatment protected mice towards bacterial and LPS induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD+administration impeded systemic IL-1β and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-β/STAT-1 signaling machinery. More importantly, NAD+administration not only improved casp-11 KO (knockout) survival but rendered WT mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD+blocking septic shock through a specific inhibition of the non-canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.
Hormone Receptor-status Prediction in Breast Cancer Using Gene Expression Profiles and Their Macroscopic Landscape
Authors: Yoon Seokhyun , Won Hye Sung , Kang Keunsoo , Qiu Kexin , Park Woong June , Ko Yoon Ho 
Published: March 2020

AbstractThe cost of next-generation sequencing technologies is rapidly declining, making RNA-seq-based gene expression profiling (GEP) an affordable technique for predicting receptor expression status and intrinsic subtypes in breast cancer (BRCA) patients. Based on the expression levels of co-expressed genes, GEP-based receptor-status prediction can classify clinical subtypes more accurately than can immunohistochemistry (IHC). Using data from the cancer genome atlas TCGA BRCA and METABRIC datasets, we identified common predictor genes found in both datasets and performed receptor-status prediction based on these genes. By assessing the survival outcomes of patients classified using GEP- or IHC-based receptor status, we compared the prognostic value of the two methods. We found that GEP-based HR prediction provided higher concordance with the intrinsic subtypes and a stronger association with treatment outcomes than did IHC-based hormone receptor (HR) status. GEP-based prediction improved the identification of patients who could benefit from hormone therapy, even in patients with non-luminal BRCA. We also confirmed that non-matching subgroup classification affected the survival of BRCA patients and that this could be largely overcome by GEP-based receptor-status prediction. In conclusion, GEP-based prediction provides more reliable classification of HR status, improving therapeutic decision making for breast cancer patients.
Detecting genomic deletions from high-throughput sequence data with unsupervised learning
Authors: Li Xin , Wu Yufeng 
Published: March 2020

AbstractStructural variation (SV), which ranges from 50 bp to ∼3 Mb in size, is an important type of genetic variations. Deletion is a type of SV in which a part of a chromosome or a sequence of DNA is lost during DNA replication. Three types of signals, including discordant read-pairs, reads depth and split reads, are commonly used for SV detection from high-throughput sequence data. Many tools have been developed for detecting SVs by using one or multiple of these signals. In this paper, we develop a new method called EigenDel for detecting genomic deletions. EigenDel first takes advantage of discordant read-pairs and clipped reads to get initial deletion candidates, and then it clusters similar candidates by using unsupervised learning methods. After that, EigenDel uses a carefully designed approach for calling true deletions from each cluster. We conduct various experiments to evaluate the performance of EigenDel on low coverage sequence data. Our results show that EigenDel outperforms other major methods in terms of improving capability of balancing accuracy and sensitivity as well as reducing bias. EigenDel can be downloaded fromhttps://github.com/lxwgcool/EigenDel.
Renewable Fatty Acid Ester Production inClostridium
Authors: Feng Jun , Zhang Jie , Feng Yiming , Wang Pixiang , Jiménez-Bonilla Pablo , Gu Yanyan , Zhou Junping , Zhang Zhong-Tian , Cao Mingfeng , Shao Zengyi , Borovok Ilya , Huang Haibo , Wang Yi 
Published: March 2020

AbstractProduction of renewable chemicals through biological routes is considered as an urgent solution for fossil energy crisis. However, endproduct toxicity inhibits microbial performance and is a key bottleneck for biochemical production. To address this challenge, here we report an example of biosynthesis of high-value and easy-recoverable derivatives to alleviate endproduct toxicity and enhance bioproduction efficiency. By leveraging the natural pathways in solventogenic clostridia for co-producing acyl-CoAs, acids and alcohols as precursors, through rational screening for host strains and enzymes, systematic metabolic engineering— including rational organization of ester-synthesizing enzymes inside of the cell, and elimination of putative prophages, we developed strains that can produce 20.3 g/L butyl acetate and 1.6 g/L butyl butyrate respectively, which were both the unprecedented levels in microbial hosts. Techno-economic analysis indicated a production cost of $986 per metric tonne for butyl acetate production from corn stover comparing to the market price of $1,200-1,400 per metric tonne of butyl acetate, suggesting the economic competitiveness of our developed bioprocess. Our principles of selecting the most appropriate host for specific bioproduction and engineering microbial chassis to produce high-value and easy-separable endproducts are highly applicable to other bioprocesses, and could lead to breakthroughs in biofuel/biochemical production and general bioeconomy.
Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis
Authors: Carey Clayton M. , Apple Sarah E. , Hilbert Zoё A. , Kay Michael S. , Elde Nels C. 
Published: March 2020

AbstractThe pathogenesis of infectious diarrheal diseases is largely attributed to enterotoxin proteins that disrupt intestinal water absorption, causing severe dehydration. Despite profound health consequences, the impacts of diarrhea-causing microbes on the evolutionary history of host species are largely unknown. We investigated patterns of genetic variation in mammalian Guanylate Cyclase-C (GC-C), an intestinal receptor frequently targeted by bacterial enterotoxins, to determine how hosts might adapt in response to diarrheal infections. Under normal conditions, GC-C interacts with endogenous guanylin peptides to promote water secretion in the intestine, but signaling can be hijacked by bacterially-encoded heat-stable enterotoxins (STa) during infection, which leads to overstimulation of GC-C and diarrhea. Phylogenetic analysis in mammals revealed evidence of recurrent positive selection in the GC-C ligand-binding domain in primates and bats, consistent with selective pressures to evade interactions with STa. Usingin vitroassays and transgenic intestinal organoids to model STa-mediated diarrhea, we show that GC-C diversification in these lineages results in substantial variation in toxin susceptibility. In bats, we observe a unique pattern of compensatory coevolution in the endogenous GC-C ligand uroguanylin, reflecting intense bouts of positive selection at the receptor-ligand interface. These findings demonstrate control of water physiology as a previously unrecognized interface for genetic conflict and reveal diarrheal pathogens as a source of selective pressure among diverse mammals.
Extracellular vesicles and their miRNA cargo in retinal health and degeneration: mediators of homeostasis, and vehicles for targeted gene therapy
Authors: Wooff Yvette , Cioanca Adrian V. , Chu-Tan Joshua A. , Aggio-Bruce Riemke , Schumann Ulrike , Natoli Riccardo 
Published: March 2020

1.1.AbstractPurposePhotoreceptor cell death and inflammation are known to occur progressively in retinal degenerative diseases, however the molecular mechanisms underlying these biological processes are largely unknown. Extracellular vesicles (EV) are essential mediators of cell-to-cell communication with emerging roles in the modulation of immune responses. EVs including exosomes encapsulate and transfer nucleic acids, including microRNA (miRNA), to recipient cells which in disease may result in dysfunctional immune responses and a loss of homeostatic regulation. In this work we investigated the role of isolated retinal small-medium sized EV (s-mEV) which includes exosomes in both the healthy and degenerating retina.MethodsIsolated s-mEV from normal retinas were characterized using dynamic light scattering, transmission electron microscopy and western blotting, and quantified across 5 days of photo-oxidative damage-induced degeneration using nanotracking analysis. Small RNAseq was used to characterize the miRNA cargo of retinal s-mEV isolated from healthy and damaged retinas. Finally, the effect of exosome inhibition on cell-to-cell miRNA transfer and immune modulation was conducted using systemic daily administration of exosome inhibitor GW4869 andin situhybridization of s-mEV-abundant miRNA, miR-124-3p. Electroretinography and immunohistochemistry was performed to assess functional and morphological changes to the retina as a result of GW4869-induced exosome depletion.ResultsResults demonstrated an inverse correlation between s-mEV secretion and photoreceptor survivability, with a decrease in s-mEV numbers following degeneration. Small RNAseq revealed that s-mEVs contained uniquely enriched miRNAs in comparison to in whole retinal tissue however, there was no differential change in the s-mEV miRNAnome following photo-oxidative damage. Exosome inhibition via the use of GW4869 was also found to exacerbate retinal degeneration, with reduced retinal function and increased levels of inflammation and cell death demonstrated following photo-oxidative damage in exosome-inhibited mice. Further, GW4869-treated mice displayed impaired translocation of photoreceptor-derived miR-124-3p to the inner retina during damage.ConclusionsTaken together, we propose that retinal s-mEV and their miRNA cargo play an essential role in maintaining retinal homeostasis through immune-modulation, and have the potential to be used in targeted gene therapy for retinal degenerative diseases.
Advice from a systems-biology model of the Corona epidemics
Authors: Westerhoff Hans V. , Kolodkin Alexey N. 
Published: March 2020

AbstractUsing standard systems biology methodologies a 14-compartment dynamic model was developed for the Corona virus epidemic. The model predicts that : (i) it will be impossible to limit lockdown intensity such that sufficient herd immunity develops for this epidemic to die down, (ii) the death toll from the SARS-CoV-2 virus decreases very strongly with increasing intensity of the lockdown, but (iii) the duration of the epidemic increases at first with that intensity and then decreases again, such that (iv) it may be best to begin with selecting a lockdown intensity beyond the intensity that leads to the maximum duration, (v) an intermittent lock down strategy should also work and be more acceptable socially and economically, (vi) an initially intensive but adaptive lockdown strategy should be most efficient, both in terms of its low number casualties and shorter duration, (vii) such an adaptive lockdown strategy offers the advantage of being robust to unexpected imports of the virus, e.g. due to international travel, (viii) the eradication strategy may still be superior as it leads to even fewer deaths and a shorter period of economic lockdown maximum, but should have the adaptive strategy as backup in case of unexpected inflation imports (ix) earlier detection of infections is perhaps the most effective way in which the epidemic can be controlled more readily, whilst waiting for vaccines.
Trainee auditors' perception of ethical climate and workplace bullying in Chinese audit firms
Authors: Liu Anthony A. 
Published: March 2020

PurposeThe purpose of this paper aims to investigate the relationship between the audit firm's ethical climate and workplace bullying perceived by trainee auditors in Chinese audit firms.Design/methodology/approachAn Ethical Climate Questionnaire and a Negative Acts Questionnaire are adapted from the existing organization studies and business ethics literature to fit in the audit firm context and are administered in a survey on 205 trainee auditors with a four-month long work placement in audit firms. SPSS is used in statistical analyses and tests.FindingsThis study confirms that some but not all types of organizational ethical climate significantly affect the perceived workplace bullying in audit firms. The results of testing for the relations between workplace bullying and ethical climate after breaking down workplace bullying into the work-related and person-related bullying sub-categories provide some different conclusions. Besides the impacts of the ethical climate on workplace bullying, this paper also finds out that trainee auditor's gender, the leader–subordinate gender difference, firm size and audit engagement team size are more likely to affect the perception of one or more of the bullying categories in audit firms.Practical implicationsThis study implies some guidance for the audit firms to establish healthy ethical climates that can help them to recruit, train and retain young skilled auditing professionals.Social implicationsThe findings of this study imply that a healthy ethical climate can help develop the audit profession and markets by deterring workplace bullying in audit firms.Originality/valueThis paper extends the organizational studies on the impact of the audit firm's organizational ethical climate on workplace bullying in the auditing profession. It also extends the gender roles in organization studies by stratifying the levels of workplace harassment.
The antecedents of entrepreneurial intention among women entrepreneurs in India
Authors: Chhabra Sakshi , Raghunathan Rajasekaran , Rao N.V. Muralidhar 
Published: March 2020

Purpose
The purpose of this paper is to understand the role of entrepreneurial intention in promoting women entrepreneurship in Indian micro, small and medium enterprises (MSMEs). This study seeks to clarify the construct of entrepreneurial intention and then reports the validation of the entrepreneurial intention instrument.

Design/methodology/approach
An instrument has been designed and administered on a sample of 103 respondents across India from women entrepreneurs to understand the entrepreneurial intention by using cluster and snowball sampling. The data has been streamlined and then analyzed using descriptive analysis for validity and reliability checks.

Findings
This research was aimed to determine the constructs of entrepreneurial intention. Through data analysis, it has been observed that the reliability coefficients reveal the adequacy of the sample. The Cronbach’s alpha values for all the items in the instrument were found to be greater than or equal to 0.6. Strong correlations were also found between direct and indirect measures of entrepreneurial intention and hence confirmed that all the measures in the instrument were well constructed. Analysis has also explained the relationship between various constructs of entrepreneurial intention by using Pearson’s correlation coefficients. Strong and positive values of correlation explain the existence of the convergent and discriminant validity of the instrument.

Research limitations/implications
The research results obtained from the analysis of reliability and validity tests not only provides the establishment of the relationship among the various constructs but also suggests that the model provides a promising potential to measure entrepreneurial intention. This study will contribute to new knowledge of the conditions of women entrepreneurship from different perspectives by developing and validating an analytic model for promoting the women entrepreneurship in MSMEs of India.

Practical implications
From a government perspective, this model will help in designing training programmes for promoting women entrepreneurship in India. The obtained result also brings significant implications for practice as well as raises a broad future direction for other researchers

Originality/value
Extended SCCT model has recently suggested an inclusive framework of factors affecting the entrepreneurial intention, there is not much attempt made in research using this theory as background for predicting intention in the context of women entrepreneurship. This paper attempts to fill this gap by formulating a conceptual model for measuring entrepreneurial intention among women entrepreneurs by integrating and adapting the constructs of extended social cognitive career theory model and entrepreneurial potential model.
A hybrid-fuzzy TOPSIS method to analyze the consumption and buying behavior of fishery and aquaculture products (FAPs) in the EU28
Authors: Cantillo Javier , Martin Juan Carlos , Román Concepción 
Published: March 2020

PurposeThe purpose of this investigation is to develop a hybrid fuzzy TOPSIS methodology in order to understand in a practical and integrated way, the consuming and buying behavior of EU residents towards Fishery and Aquaculture Products (FAPs), with an emphasis in the consumption and buying frequency.Design/methodology/approachData were obtained from the Special Eurobarometer Survey (European Union, 2018b), which is a survey of 27,732 EU residents with different socio-demographic characteristics that represent the 28 EU countries. A hybrid fuzzy TOPSIS methodology that synthesizes the consuming and buying behavior of the EU residents toward FAPs was developed.FindingsThe results show that among the countries, Spain has the highest consumption and buying patterns of FAPs, while among the generations it corresponds to the residents born between 1928 and 1945. In addition, there are important differences that depend on the country of residence as well as the generation of the residents. The elasticity analysis evidenced that marketing strategies would have the biggest impact in the countries located in the Central-Eastern zone of the EU and on the generation formed by the people born after 1980.Originality/valueAlthough in the literature there are many studies that aimed to understand the behavior of consumers for FAPs, few investigations have focused on analyzing and integrating both the consumption and buying behavior, and to our best knowledge, there are no studies providing a methodology that allow making comparisons between different countries regarding the consumption and buying behavior of FAPs.
Corporate governance in the largest family firms in Latin America
Authors: Vazquez Pedro , Carrera Alejandro , Cornejo Magdalena 
Published: March 2020

PurposeThe aim of this study is to explore and understand corporate governance patterns in family firms across Latin America. This is in response to several calls in the academic literature urging for more empirical studies in corporate governance in developing regions.Design/methodology/approachFollowing a configurative perspective, a hierarchical cluster analysis is applied to a sample of the 155 largest Latin American family firms.FindingsThe authors identify three main corporate governance configurations across Latin American countries. First, the exported governance model resembles many characteristics of Anglo-American and Continental Europe governance patterns of public listed control, having independence from the board of directors, and mainly hiring non-family management. Second, the super-familial governance model describes private ownership where one or multiple families control both the board of directors and the top-management team. Finally, the hybrid governance model is the largest cluster identified in the sample and combines governance characteristics of both of the foregoing configurations. This configuration exhibits ownership structured through public offerings of shares combined with leadership of the board of directors by a family member as well as moderate family influence on the board and management.Originality/valueThis is the first study to investigate corporate governance in the largest listed and privately-owned family firms in Latin America. The article extends the conversation on family firm heterogeneity and contributes to the configurative approach in the family business field by offering a cross-country perspective and identifying meaningful taxonomies that are applicable beyond national boundaries.