bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bacterial leader peptide peTrpL has a conserved function in antibiotic-dependent posttranscriptional regulation of ribosomal genes
Authors: Melior Hendrik , Maaß Sandra , Stötzel Maximilian , Li Siqi , Förstner Konrad U. , Schütz Rubina , Azarderakhsh Saina , Shevkoplias Aleksei , Barth-Weber Susanne , Varadarajan Adithi R. , Baumgardt Kathrin , Chervontseva Zoe , Ziebuhr John , Ahrens Christian H. , Becher Dörte , Evguenieva-Hackenberg Elena 
Published: April 2019

SummaryThe ribosome-dependent attenuator located upstream of bacterial tryptophan biosynthesis genes harbors a small ORF trpL containing tryptophan codons. When tryptophan is available, efficient trpL translation causes transcription termination and release of the attenuator RNA rnTrpL. In Sinorhizobium meliloti, rnTrpL is a trans-acting sRNA. Here, we identified an evolutionary conserved function for the trpL-encoded 14-aa leader peptide peTrpL. Upon exposure to tetracycline, the cellular peTrpL levels were increased and rnTrpL was generated independently of tryptophan availability. Both peTrpL and rnTrpL were found to be involved in tetracycline-dependent destabilization of rplUrpmA mRNA encoding ribosomal proteins L21 and L27. We provide evidence for redirection of the sRNA rnTrpL from its antibiotic-independent target trpDC to rplUrpmA by formation of an antibiotic-dependent ribonucleoprotein complex (ARNP). ARNPs comprising peTrpL, rnTrpL, rplUrpmA and antisense RNA were also observed for other translation-inhibiting antibiotics, suggesting that bacteria evolved mechanisms to utilize antibiotics for mRNA destabilization.
Iba1+Microglia Exhibit Morphological Differences between Inferior Colliculus Sub-Regions and Their Abutments ontoGAD67+Somata Reveal Two Novel Sub-types of GABAergic Neuron
Authors: Webb Samuel David , Orton Llwyd David 
Published: April 2019

AbstractMicroglia have classically been viewed as the endogenous phagocytes of the brain, however, emerging evidence suggests roles for microglia in the healthy, mature nervous system. We know little of the contribution microglia make to ongoing processing in sensory systems. To exploreIba1+microglial diversity, we employed the inferior colliculi (IC) as model nuclei, as they are characterized by sub-regions specialized for differing aspects of auditory processing. We conducted fluorescent multi-channel immunohistochemistry and confocal microscopy in guinea pigs of both sexes and discovered that the density and morphology ofIba1+labelling varied between parenchymal sub-regions of IC, whileGFAP+labelling of astrocytes was confined to theglia limitans externaandperi-vascular regions. The density ofIba1+microglia somata was similar across sub-regions, however a greater amount of labelling was found in dorsal cortex than ventral central nucleus or lateral cortex. To further understand these differences between sub-regions in IC, Sholl and skeleton analyses of individual microglia revealed a greater number of branching ramifications in dorsal cortex. We also quantified abutments ofIba1+microglial processes ontoGAD67+(putative GABAergic) somata. Cluster analyses revealed two novel sub-types ofGAD67+neuron, which can be distinguished solely based on the quantity of axo-somaticIba1+abutments they receive. These data demonstrateIba1+microglia exhibit different morphologies and interactions withGAD67+neurons in distinct sub-regions of the mature, healthy IC. Taken together, these findings suggest significant heterogeneity amongst microglia in the auditory system, possibly related to the ongoing functional demands of their niche.
The BLIMP1 – EZH2 nexus in a non-Hodgkin lymphoma
Authors: Anderson Kimberley Jade , Ósvaldsdóttir Árný Björg , Atzinger Birgit , Traustadóttir Gunnhildur Ásta , Nolling Jensen Kirstine , Lárusdóttir Aðalheiður Elín , Bergþorsson Jón Þór , Harðardóttir Ingibjörg , Magnúsdóttir Erna 
Published: April 2019

AbstractWaldenström’s macroglobulinemia (WM) is a non-Hodgkin lymphoma, resulting in antibody-secreting lymphoplasmacytic cells in the bone marrow and pathologies resulting from high levels of monoclonal immunoglobulin M (IgM) in the blood. Despite the key role for BLIMP1 in plasma cell maturation and antibody secretion, its potential role in WM cell biology has not yet been explored. Here we provide evidence of a crucial role for BLIMP1 in the survival of WM cells and further demonstrate that BLIMP1 is necessary for the expression of the histone methyltransferase EZH2 in both WM and multiple myeloma. The effect of BLIMP1 on EZH2 levels is post translational, at least partially through the regulation of proteasomal targeting of EZH2. Chromatin immunoprecipitation analysis and transcriptome profiling suggest that the two factors co-operate in regulating genes involved in cancer cell immune evasion. Co-cultures of natural killer cells and WM cells further reveal that both factors participate directly in immune evasion, promoting escape from natural killer cell mediated cytotoxicity. Together, the interplay of BLIMP1 and EZH2 plays a vital role in promoting the survival of WM cells.
DeeplyEssential: A Deep Neural Network for Predicting Essential Genes in Microbes
Authors: Hasan Md Abid , Lonardi Stefano 
Published: April 2019

AbstractEssential genes are genes that critical for the survival of an organism. The prediction of essential genes in bacteria can provide targets for the design of novel antibiotic compounds or antimicrobial strategies. Here we propose a deep neural network (DNN) for predicting essential genes in microbes. Our DNN-based architecture called DeeplyEssentialmakes minimal assumptions about the input data (i.e., it only uses gene primary sequence and the corresponding protein sequence) to carry out the prediction, thus maximizing its practical application compared to existing predictors that require structural or topological features which might not be readily available. Our extensive experimental results show that DeeplyEssentialoutperforms existing classifiers that either employ down-sampling to balance the training set or use clustering to exclude multiple copies of orthologous genes. We also expose and study a hidden performance bias that affected previous classifiers.The code of DeeplyEssentialis freely available athttps://github.com/ucrbioinfo/DeeplyEssential
Environment Shapes the Accessible Daptomycin Resistance Mechanisms inEnterococcus faecium
Authors: Prater Amy G. , Mehtaa Heer , Kosgei Abigael J. , Miller William R. , Tran Truc T. , Arias Cesar A. , Shamoo Yousif 
Published: April 2019

AbstractDaptomycin binds to bacterial cell membranes and disrupts essential cell envelope processes leading to cell death. Bacteria respond to daptomycin by altering their cell envelopes to either decrease antibiotic binding to the membrane or by diverting binding away from vulnerable septal targets to remodeled anionic phospholipid membrane patches. InEnterococcus faecalis, daptomycin resistance is typically coordinated by the three-component cell-envelope-stress-response system, LiaFSR. Here, studying a clinical strain of multidrug-resistantEnterococcus faeciumcontaining alleles associated with activation of the LiaFSR signaling pathway, we found that specific environments selected for different evolutionary trajectories leading to high-level daptomycin resistance. Planktonic environments favored pathways that increased cell surface charge viayvcRSupregulation ofdltABCDandmprF, causing a reduction in daptomycin binding. Alternatively, environments favoring complex structured communities, including biofilms, evolved both diversion and repulsion strategies viadivIVAandoatAmutations, respectively. Both environments subsequently converged on cardiolipin synthase (cls) mutations, suggesting the importance of membrane modification across strategies. Our findings indicate thatE. faeciumcan evolve diverse evolutionary trajectories to daptomycin resistance that are shaped by the environment to produce a combination of resistance strategies. The accessibility of multiple and different biochemical pathways simultaneously suggests that the outcome of daptomycin exposure results in a polymorphic population of resistant phenotypes makingE. faeciuma recalcitrant pathogen.
EPAC2 is required for corticotropin-releasing hormone-mediated spine loss
Authors: Xie Zhong , Penzes Peter , Srivastava Deepak P. 
Published: April 2019

AbstractCorticotropin-releasing hormone (CRH) is produced in response to stress. This hormone plays a key role in mediating neuroendocrine, behavioral, and autonomic responses to stress. The CRH receptor 1 (CRHR1) is expressed in multiple brain regions including the cortex and hippocampus. Previous studies have shown that activation of CRHR1 by CRH results in the rapid loss of dendritic spines. Exchange protein directly activated by cAMP (EPAC2, also known as RapGEF4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rap, has been linked with CRHR1 signaling. EPAC2 plays a critical role in regulating dendritic spine morphology and number in response to several extracellular signals. But whether EPAC2 links CRHR1 with dendritic spine remodeling is unknown. Here we show that CRHR1 is highly enriched in the dendritic spines of primary cortical neurons. Furthermore, we find that EPAC2 and CRHR1 co-localize in cortical neurons. Critically, short hairpin RNA-mediated knockdown of Epac2 abolished CRH-mediated spine loss in primary cortical neurons. Taken together, our data indicate that EPAC2 is required for the rapid loss of dendritic spines induced by CRH. These findings identify a novel pathway by which acute exposure to CRH may regulate synaptic structure and ultimately responses to acute stress.
PRDM1 controls the sequential activation of neural, neural crest and sensory progenitor determinants by regulating histone modification
Authors: Prajapati Ravindra S. , Hintze Mark , Streit Andrea 
Published: April 2019

ABSTRACTDuring early embryogenesis, the ectoderm is rapidly subdivided into neural, neural crest and sensory progenitors. How the onset of lineage-specific determinants and the loss of pluripotency markers are temporally and spatially coordinated in vivo remains an open question. Here we identify a critical role for the transcription factor PRDM1 in the orderly transition from epiblast to defined neural lineages. Like pluripotency factors,PRDM1is expressed in all epiblast cells prior to gastrulation, but lost as they begin to differentiate. We show that, unlike pluripotency factors, PRDM1 is initially required for the activation of neural, neural crest and sensory progenitor specifiers and for the downregulation of pluripotency-associated genes. In vivo chromatin immunoprecipitation reveals stage-specific binding of PRDM1 to regulatory regions of neural and sensory progenitor genes, PRDM1-dependent recruitment of the histone demethylase Kdm4a to these regions and associated removal of repressive histone marks. Once lineage determinants become expressed, they repressPRDM1, and our data suggest thatPRDM1downregulation is required for cells to maintain their identity. Thus, PRDM1 mediates chromatin modifications that directly control neural and sensory progenitor genes, and its activities switch from an activator at early stages to a repressor once neural fates have been established.
Brain age prediction reveals aberrant brain white matter in schizophrenia and bipolar disorder: A multi-sample diffusion tensor imaging study
Authors: Tønnesen Siren , Kaufmann Tobias , de Lange Ann-Marie , Richard Genevieve , Doan Nhat Trung , Alnæs Dag , van der Meer Dennis , Rokicki Jaroslav , Moberget Torgeir , Maximov Ivan I. , Agartz Ingrid , Aminoff Sofie R. , Beck Dani , Barch Deanna , Beresniewicz Justyna , Cervenka Simon , Bergman Helena Fatouros , Craven Alexander R. , Flyckt Lena , Gurholt Tiril P. , Haukvik Unn K. , Hugdahl Kenneth , Johnsen Erik , Jönsson Erik G. ,   KaSPi, Kolskår Knut K. , Kompus Kristiina , Kroken Rune Andreas , Lagerberg Trine V. , Løberg Else-Marie , Nordvik Jan Egil , Sanders Anne-Marthe , Ulrichsen Kristine , Andreassen Ole A. , Westlye Lars T. 
Published: April 2019

AbstractBackgroundSchizophrenia (SZ) and bipolar disorders (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, BD, and healthy controls across 10 cohorts.MethodsWe trained six cross-validated models using different combinations of DTI data from 927 healthy controls (HC, 18-94 years), and applied the models to the test sets including 648 SZ (18-66 years) patients, 185 BD patients (18-64 years), and 990 HC (17-68 years), estimating brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.Results10-fold cross-validation revealed high accuracy for all models. Compared to controls, the model including all feature sets significantly over-estimated the age of patients with SZ (d=-.29) and BD (d=.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy (FA) based models showed larger group differences than the models based on other DTI-derived metrics.ConclusionsBrain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.
Organizations need ethical leaders: how to attract and nurture cultural creatives into positions of leadership and influence
Authors: Gardner Paula Kay , Holloway Mark 
Published: April 2019

Purpose
This paper aims to look at the growing need for ethical leaders, suggesting that a strata of society called “cultural creatives” may answer that need. It investigates how the cultural creatives can be attracted and nurtured in positions of leadership and puts forward tangible action points and suggestions to help organizations take practical actions.

Design/methodology/approach
The paper is an interpretative phenomenological analysis of four cultural creatives who are in positions of leadership.

Findings
The finding with the maximum impact for organizations perhaps is that they all left positions where they felt unsupported and undeveloped, rather than push their employer for that support. Participants were predictably people-oriented, although this meant different things for each person. Their styles of leadership varied, but all shared a desire to become role models and leave a legacy. Only one worked within the third sector, and all were quite pragmatic and motivated by money, something that seems to be different from the original research on this group.

Practical implications
The paper highlights five key indicators organizations must consider to attract and nurture cultural creatives: flexibility in leadership style, levels of autonomy, acting as mentors, appropriate financial rewards, and opportunities for authentic, self-determined work.

Social implications
The cultural creatives are reportedly the third largest social strata in Western society, after the modernists and traditionalists. They are growing as a group, and this study looks at how they operate and feel about their workplace. It provides insights into what it is like to be a cultural creative.

Originality/value
This is the only known research on cultural creatives since the original research in the early 2000s.
Southern European welfare states and homelessness: Portugal and Greece
Authors: Kourachanis Nikos 
Published: April 2019

PurposeThe purpose of this paper is to compare homelessness policies in Portugal and Greece.Design/methodology/approachAfter a brief overview of the relationship between welfare regimes and homelessness, the characteristics of homelessness policies within the South-European regime are studied. Subsequently, by employing empirical data, a comparison between the homelessness policies of these two countries is attempted through three axes of analysis: the historical emergence of homelessness policies; the impact of the memoranda, as a series of fiscal measures associated with welfare retrenchment, on the deterioration of homelessness; and the characteristics of the social policies being developed.FindingsIt is noted that the two countries consolidate a residual social intervention model that fails to address homelessness adequately.Originality/valueThis is the first attempt to compare homelessness policies between Portugal and Greece.
Pricing power in insurance markets: evidence from South Africa
Authors: Alhassan Abdul Latif , Biekpe Nicholas 
Published: April 2019

PurposeIn less competitive markets, firms with market power are likely to exercise pricing power by setting output prices above their marginal cost, inducing welfare losses from resource misallocation, managerial inefficiency and market instability. In order to address such market imperfections, it is important for regulatory authorities to identify the sources of pricing power and devise policies to address their adverse effects. In this context, the purpose of this paper is to undertake an empirical analysis to identify the determinants of pricing power in the South African non-life insurance market.Design/methodology/approachThe authors estimate the Lerner competitive index as the proxy for pricing power using annual data on 79 firms from 2007 to 2012. In the second stage, the paper employs panel regression techniques in the ordinary least squares, random effects and generalised method of moment’s estimations to examine the effect of insurer level characteristics on pricing power.FindingsThe authors find the market to be characterised by firms with high pricing power. Domestic-owned insurers are found to exercise high pricing power compared with foreign-owned insurers. The authors also identify size, cost efficiency, product line diversification, market concentration, leverage and reinsurance contracts as the significant predictors of pricing power in the market. Finally, through a quantile regression analysis, the authors find the effect of cost efficiency, business line diversification and reinsurance to be heterogeneous across different quantiles of pricing power.Practical implicationsThe findings provide regulatory authorities with useful indicators in addressing anti-competitive behaviour in high pricing power to enhance the stability of the insurance market and improve consumer welfare and economic development.Originality/valueTo the best of the authors’ knowledge, this is first paper to examine the determinants of pricing power and competitive behaviour in an insurance market.
Corporate debt maturity and economic development
Authors: Álvarez-Botas Celia , González-Méndez Víctor M. 
Published: April 2019

Purpose
The purpose of this paper is to analyse the effect of economic development on the influence of country-level determinants on corporate debt maturity, bearing in mind firm size and the period of financial crisis.

Design/methodology/approach
The authors employ panel data estimation with fixed effects to examine the role of economic development in influencing the relationship between country-level determinants on corporate debt maturity. The paper uses a sample of 30,727 listed firms, belonging to 39 countries, over the period 2005–2012.

Findings
Corporate debt maturity increases with the efficiency of the legal system and bank concentration and decreases with the weight of banks in the economy. However, the importance of these country determinants is greater in developing than in developed countries. The authors also show that firm size in developed and developing countries influences country determinants of corporate debt maturity. Finally, the results reveal that the financial crisis has affected the debt maturity of firms differently in developed and developing countries, with the effect of bank concentration lengthening debt maturity, this effect being more pronounced in developing countries.

Practical implications
The findings provide useful insights to guide policy decisions providing access to long-term financing, as corporate debt maturity depends on economic development, institutional environment, banking structure and firm size.

Originality/value
This study incorporates economic development in explaining the relationship between country-level determinants and corporate debt maturity.
Tax avoidance in management-owned firms: evidence from Brazil
Authors: Cabello Otávio Gomes , Gaio Luiz Eduardo , Watrin Christoph 
Published: April 2019

PurposeThe purpose of this paper is to test if companies with a greater concentration of management ownership (and thus more risk-averse managers) avoid less tax.Design/methodology/approachThe authors use a regression analysis with panel data, using as a sample of Brazilian companies from 2001 to 2015. The authors investigate the impact of insider ownership on tax avoidance, testing how and how much different ownership levels of inside owner are associated with tax avoidance measured by effective tax rates and book-tax differences.FindingsThe results indicate that different levels of management ownership are associated with different levels of tax avoidance behavior.Originality/valueThis paper contributes to the literature showing that ownership and decision making are not always focused on only a few decision makers. The owners are likely to be more risk averse and therefore less willing to invest in risky projects such as tax avoidance.
Intergenerational transmission of human capital
Authors: Uddin Md Nasir 
Published: April 2019

Purpose
The purpose of this paper is to find the rate of intergenerational transmission of human capital and comparative schooling attainment between lower and higher income families using the labor force survey in Thailand.

Design/methodology/approach
Instrumental variable (IV) approach has been used in this paper. The author proposed an alternative instrument for parental education to identify the rate of transmission, which is the parents’ cohorts’ mean schooling in their respective provinces.

Findings
This paper found that the rate of transmission of human capital from father is higher than that from mother in Thailand. For both, the rate of transmission in Thailand is higher than that in the developed countries. In addition, it is found that children from lower income families are getting lesser education than those from higher income families in Thailand.

Research limitations/implications
This paper is used as an alternative instrument that could solve the endogeneity problem in the literature of intergenerational transmission of human capital.

Practical implications
The results of rate of transmission can help to make educational policies in countries like Thailand. It also could help the policymakers to evaluate and redesign the student loan scheme (SLS) in Thailand.

Originality/value
This study is used as an alternative instrument for parental education to identify the rate of transmission in an IV approach. This paper is the first to identify the intergenerational transmission rate in Thailand. In addition, it evaluates Thai SLS in an intergenerational framework.