bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic chemogenetic activation of forebrain excitatory neurons in postnatal life evokes long-lasting changes in mood-related behavior
Authors: Pati Sthitapranjya , Saba Kamal , Salvi Sonali S. , Tiwari Praachi , Chaudhari Pratik R. , Verma Vijaya , Mukhopadhyay Sourish , Kapri Darshana , Suryavanshi Shital , Clement James P. , Patel Anant B. , Vaidya Vidita A. 
Published: February 2020

AbstractEarly adversity is a key risk factor for the development of adult psychopathology, including anxiety, depression and schizophrenia. Rodent models of early adversity program persistent behavioral, molecular, metabolic, and neurophysiological changes. Perturbed signaling via forebrain Gq-coupled neurotransmitter receptors is a common feature across multiple models of early adversity. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke long-lasting mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated chemogenetic activation of CamKIIα-positive forebrain excitatory neurons during postnatal life (P2-14) increased anxiety- and despair-like behavior, and evoked sensorimotor gating deficits in adulthood. In contrast, chronic chemogenetic hM3Dq DREADD activation of forebrain excitatory neurons in the juvenile or adult window did not evoke any mood-related behavioral alterations, highlighting the criticality of the postnatal temporal window. The enhanced anxiety-, despair- and schizophrenia-like behavioral changes evoked by chronic chemogenetic activation of forebrain excitatory neurons in postnatal life, was accompanied by an increased cortical and hippocampal metabolic rate of glutamatergic and GABAergic neurons in adulthood. Furthermore, animals with a history of postnatal hM3Dq activation exhibited a decline in the expression of activity-dependent and plasticity-associated markers within the hippocampus, along with perturbed hippocampal excitatory and inhibitory currents in adulthood. These results indicate that Gq signaling mediated activation of forebrain excitatory neurons during the critical postnatal window is sufficient to program altered mood-related behavior, as well as metabolic and neurophysiological changes in forebrain glutamate and GABA systems, recapitulating specific aspects of the consequences of early adversity.
High-throughput laboratory evolution and evolutionary constraints inEscherichia coli
Authors: Maeda Tomoya , Iwasawa Junichiro , Kotani Hazuki , Sakata Natsue , Kawada Masako , Horinouchi Takaaki , Sakai Aki , Tanabe Kumi , Furusawa Chikara 
Published: February 2020

SUMMARYUnderstanding the constraints that shape the evolution of antibiotic resistance is critical for predicting and controlling drug resistance. Despite its importance, however, a systematic investigation for evolutionary constraints is lacking. Here, we performed a high-throughput laboratory evolution ofEscherichia coliunder the addition of 95 antibacterial chemicals and quantified the transcriptome, resistance, and genomic profiles for the evolved strains. Using interpretable machine learning techniques, we analyzed the phenotype-genotype data and identified low dimensional phenotypic states among the evolved strains. Further analysis revealed the underlying biological processes responsible for these distinct states, leading to the identification of novel trade-off relationships associated with drug resistance. We also report a novel constraint that leads to decelerated evolution. These findings bridge the genotypic, gene expression, and drug resistance space and lead to a better understanding of evolutionary constraints for antibiotic resistance.
Cooption of polyalanine tract into a repressor domain in the mammalian transcription factor HoxA11
Authors: Lynch Vincent J. , Wagner Gunter P. 
Published: February 2020

AbstractAn enduring problem in biology is explaining how the functions of genes originated and how those functions diverge between species. Despite detailed studies on the functional evolution of a few proteins, the molecular mechanisms by which protein functions have evolved are almost entirely unknown. Here we show that a polyalanine tract in the homeodomain transcription factor HoxA11 arose in the stem-lineage of mammals and functions as an autonomous repressor module by physically interacting with the PAH domains of SIN3 proteins. These results suggest that long polyalanine tracts, which are common in transcription factors and often associated with disease, may generally function as repressor domains and can contribute to the diversification of transcription factor functions despite the deleterious consequences of polyalanine tract expansion.Research HighlightsWe show that a polyalanine track in HoxA11 evolved into a repressor domain in mammals through an increase in alanine repeat number, indicating that transcription factors can evolve novel functions despite the potential deleterious consequences associated with amino acid repeats.
Targeting HIV Env immunogens to B cell follicles in non-human primates through immune complex or protein nanoparticle formulations
Authors: Martin Jacob T. , Cottrell Christopher A. , Antanasijevic Aleksandar , Carnathan Diane G. , Cossette Benjamin J. , Enemuo Chiamaka A. , Gebru Etse H. , Choe Yury , Viviano Federico , Tokatlian Talar , Cirelli Kimberly M. , Ueda George , Copps Jeffrey , Schiffner Torben , Menis Sergey , Schief William R. , Crotty Shane , King Neil P. , Baker David , Silvestri Guido , Ward Andrew B. , Irvine Darrell J. 
Published: February 2020

AbstractFollowing immunization, high affinity antibody responses develop within germinal centers (GCs), specialized sites within follicles of the lymph node (LN) where B cells proliferate and undergo somatic hypermutation. Antigen availability within GCs is important, as B cells must acquire and present antigen to follicular helper T cells to drive this process. However, recombinant protein immunogens such as soluble HIV envelope (Env) trimers do not efficiently accumulate in follicles following traditional immunization. Here we demonstrate two strategies to concentrate HIV Env immunogens in follicles, via the formation of immune complexes (ICs) or by employing self-assembling protein nanoparticles for multivalent display of Env antigens. Using rhesus macaques, we show that within a few days following immunization, free trimers were present in a diffuse pattern in draining LNs, while trimer ICs and Env nanoparticles accumulated in B cell follicles. Whole LN imaging strikingly revealed that ICs and trimer nanoparticles concentrated in as many as 500 follicles in a single lymph node within 2 days after immunization. Imaging of LNs collected 7 days post-immunization showed that Env nanoparticles persisted on follicular dendritic cells in the light zone of nascent germinal centers. These findings suggest that the form of antigen administered in vaccination can dramatically impact localization in lymphoid tissues and provides a new rationale for the enhanced immune responses observed following immunization with immune complexes or nanoparticles.
Comprehensive exploration of the translocation, stability and substrate recognition requirements in VIM-2 lactamase
Authors: Chen J. Z. , Fowler D.M. , Tokuriki N. 
Published: February 2020

AbstractMetallo-β-lactamases (MBLs) degrade a broad spectrum of β-lactam antibiotics, and are a major disseminating source for multidrug resistant bacteria. Despite many biochemical studies in diverse MBLs, molecular understanding of the roles of residues in the enzyme’s stability and function, and especially substrate specificity, is lacking. Here, we employ deep mutational scanning (DMS) to generate comprehensive single amino acid variant data on a major clinical MBL, VIM-2, by measuring the effect of thousands of VIM-2 mutants on the degradation of three representative classes of β-lactams (ampicillin, cefotaxime, and meropenem) and at two different temperatures (25°C and 37°C). We revealed residues responsible for expression and translocation, and mutations that increase resistance and/or alter substrate specificity. The distribution of specificity-altering mutations unveiled distinct molecular recognition of the three substrates. Moreover, these function-altering mutations are frequently observed among naturally occurring variants, suggesting that the enzymes has continuously evolved to become more potent resistance genes.
Swine Growth Promotion with Antibiotics or Alternatives can Increase Antibiotic Resistance Gene Mobility Potential
Authors: Muurinen Johanna , Richert Jacob , Wickware Carmen , Richert Brian , Johnson Timothy A. 
Published: February 2020

AbstractEven though the use of antibiotics for food-producing animals may contribute to the emergence of antimicrobial resistance, antibiotics are still used as growth promoters. Due to consumer and regulatory pressures, the use of alternatives to antibiotics as growth promoters is increasing, thus more information is needed on their capability to disseminate antimicrobial resistance compared to antibiotics. We investigated the impacts of carbadox (antibiotic), copper sulfate and zinc oxide (metals) and mushroom powder (natural product) on the pig fecal resistome and microbiome. Antibiotic resistance gene (ARG) and mobile genetic element (MGE) abundances were measured using a high-throughput qPCR array with 382 primer pairs. Bacterial community composition was determined by 16S rRNA gene sequencing. More ARGs co-occurred with MGEs in the growth promoter group samples than in the control group samples. Community composition could not be linked to resistome in the growth promoter group samples, indicating a potential decoupling of ARGs and phylogeny. Additionally, machine-learning methods aided in defining the community and resistome differences in response to treatments. Since increased ARG mobility potential was the primary response to the dietary additives used in this study, we suggest that ARG mobility should be considered when designing antimicrobial use policies and antimicrobial resistance surveillances.
Genetic architecture of oxidative stress tolerance in the fungal wheat pathogenZymoseptoria tritici
Authors: Zhong Ziming , McDonald Bruce A. , Palma-Guerrero Javier 
Published: February 2020

ABSTRACTReactive oxygen species are toxic byproducts of aerobic respiration produced during cell growth. They also are an important component of plant defenses to inhibit microbial pathogens. Tolerance to oxidative stress contributes to viability and pathogenicity of plant pathogens. However, the complex molecular network of oxidative stress responses hinders identification of the genes contributing to variation in this trait. Variation in genes affecting responses to oxidative stress is likely to affect the evolutionary potential of pathogen tolerance to host defences. Here, we employed a forward genetic approach to investigate the genetic architecture of oxidative stress tolerance in the fungal wheat pathogenZymoseptoria tritici. By performing quantitative trait locus (QTL) mapping in two crosses, we identified several genomic regions associated with tolerance to oxidative stress, including a QTL having a large effect on growth under oxidative stress. We found evidence for a significant trade-off between growth under non-stressful conditions and growth inhibition under oxidative stress. We identified a large QTL associated with this trade-off and with growth under non-stressful conditions, suggesting that differences in fungal growth could result in different sensitivities to oxidative stress. Our results suggest that genes related to fungal growth could also contribute to variation in oxidative stress tolerance among fungal strains.
Parallel CRISPR-Cas9 screens clarify impacts of p53 on screen performance
Authors: Bowden Anne Ramsay , Juarez David A. Morales , Sczaniecka-Clift Matylda , Agudo Maria Martin , Lukashchuk Natalia , Thomas John C. , Jackson Stephen P. 
Published: February 2020

AbstractCRISPR-Cas9 genome engineering has revolutionised high-throughput functional genomic screens. However, recent work has raised concerns regarding the performance of CRISPR-Cas9 screens usingTP53wild-type human cells due to a p53-mediated DNA damage response (DDR) limiting the efficiency of generating viable edited cells. To directly assess the impact of cellular p53 status on CRISPR-Cas9 screen performance, we carried out parallel CRISPR-Cas9 screens in wild-type andTP53knockout human retinal pigment epithelial cells using a focused dual guide RNA library targeting 852 DDR-associated genes. Our work demonstrates that although functional p53 status negatively affects identification of significantly depleted genes, optimal screen design can nevertheless enable robust screen performance. Through analysis of our own and published screen data, we highlight key factors for successful screens in both wild-type and p53-deficient cells.
The Myth of “Hong Kong Nationalism”
Authors: Loo Jeff Hai-chi 
Published: February 2020

PurposeThe persistent growth of ‘nativists’ in Hong Kong not only highlighted people's consideration over mainlandization, it also stimulates Beijing's nerve on national security. This paper adopts a critical perspective to explore the development of ‘Hong Kong Nationalism’ that emerged in 2015. It will show the development of ‘Hong Kong nationalism’ is a phenomenon compounded by the creation of critical academics, government exaggeration, and pro-Beijing media labeling. In fact, this phenomenon leads to the suppression of political space for critical opposition.Design/methodology/approachThe interaction between Hong Kong Special Administrative Region (HKSAR) government, central government, critical academics, and pro-Beijing media will be used to adopt a conceptual framework to show how their interrelationship would derive tremendous impacts to the development of ‘Hong Kong Nationalism.’ It will further investigate some implications for the further political development in Hong Kong.FindingsThe development of ‘Hong Kong Nationalism’ illustrates the triangular relations between critical academic, HKSAR and the Beijing government, and pro-Beijing media. The critical academics create and imagine such ‘Hong Kong Nationalism’ with Hong Kong's political destiny that stimulates the nerve of Beijing and HKSAR on territorial integrity. The ‘imagined nationalism’ advocated by critical and opposition academics and advanced by the activists not only opened the Pandora's box that derives a Trojan horse scenario for the development of pan-democratic camp which affects the democracy movement tremendously.OriginalityThis paper is the first academic paper to explore ‘Hong Kong Nationalism’ through analyzing the discourse advocated by critical academics. This paper can also fill in the gap from existing literature about social movement in Hong Kong as most of them ignored the influence of radical nativist movement.
Sub-national consumer ethnocentrism and the importance of the origin of food products: an exploratory analysis
Authors: Fernández-Ferrín Pilar , Bande Belén , Martín-Consuegra David , Díaz Estrella , Kastenholz Elisabeth 
Published: February 2020

PurposeThis study's main objective is to analyse the role of the consumer's ethnocentrism as a potential segmentation basis and to detect product origin-sensitive groups. The relationship between the consumer's regional ethnocentrism, local and regional identity and corresponding valuation and purchase of food products from a region is also examined.Design/methodology/approachThe responses of 358 consumers residing in two Spanish regions are analysed by means of a mediation analysis and a cluster analysis.FindingsThe results suggest the convenience of considering ethnocentric consumer tendencies, also at the regional level, when studying attitudes, valuation, information search and effective purchase of foods of diverse categories and origins.Originality/valueThe main contributions of this work derive from the assessment of consumer ethnocentrism at a subnational level (which is much less present in the literature) and the evidence of its usefulness for segmenting the market and detecting groups of origin-sensitive consumers, which can be useful to companies that produce and market food products in different regions.
The Brexit dilemma for small business: European companies respond
Authors: Barron Andrew , Boutary Martine 
Published: February 2020

Purpose
Focusing on the internationalization decisions of firms, this paper aims to investigate how managers of small and medium-sized enterprises (SMEs) interpret and respond to exogenous shocks in their international sales markets. The authors specifically explore the effects of cognitive factors on French SME managers’ strategic decisions in response to the UK’s decision to leave the EU.

Design/methodology/approach
The research applies insights gleaned from the field of behavioral strategy, brought to life with illustrative examples of SME managers’ perceptions of Brexit derived from secondary and primary data sources.

Findings
The authors find that a combination of decision-makers’ previous experience and emotions can help account for their interpretations and strategic responses to Brexit.

Practical implications
The research highlights the need for managers to be more aware of how their personal characteristics can influence their mindsets and shape how they choose to respond to uncertain and ambiguous developments in foreign markets.

Originality/value
The research exposes important, behavioral dimensions of decision-making, which remain under-explored in the existing international business literature.
Can you balance the gaps? Ambidexterity in service firms
Authors: Öberg Christina , Kollberg Beata 
Published: February 2020

PurposeAmbidexterity refers to the ability to balance contradictory items and has been extensively described in relation to technological advancement in large-sized manufacturing firms. Few studies on hospitality and tourism firms have described the balancing of innovative developments, often focusing on the operational level of firms. Ambidexterity could though be understood also in dimensions of customer/market development and collaborative interaction. This paper describes and discusses ambidexterity in the dimensions of technological advancement, customer/market development and collaborative interaction in service firms to inspire this debate and bridge the gap between strategy and the service field.Design/methodology/approachA case study describing a service firm's 25-year development functions as the empirical source of inspiration to understand how service firms also in tourism and hospitality sectors would work with strategies and their developments related to technology, customers and collaboration. The case study is analysed using an activity-based time schedule to capture dimensions of ambidexterity and how they are linked to one another.FindingsThe findings indicate how the service firm balanced exploitation and exploration over time, rather than allowing such activities to occur simultaneously and in parallel. Generally, the firm only managed to explore in one dimension at the time.Originality/valueThe paper broadens the lens on ambidexterity to include collaboration and customer involvement and the link among the various dimensions of ambidexterity. It also discusses how ambidexterity in these dimensions may be handled by service firms so as to inspire strategic developments among tourism and hospitality firms.
Competition and market structure of the Malaysian Islamic banking industry
Authors: Basri Mohd Faizal 
Published: February 2020

Purpose
This paper aims to investigate the impact of competition in the Malaysian Islamic banking industry and the market structure of the industry by focusing on the particular impact created by the entrance of fully fledged foreign Islamic banks plus the introduction of Islamic subsidiaries of existing conventional banks in the country (domestic and foreign ownership).

Design/methodology/approach
Using a sample of 16 Islamic banks in the country that operated between 2008 and 2015, this paper measures the competition among the Islamic banks using the Panzar-Rosse Model and by looking at the market structure of the industry using the k-bank concentration ratio and the Herfindahl-Hirschman Index.

Findings
The study found that between 2008 and 2015, the Malaysian Islamic banking industry operated in monopolistic competition conditions with a moderately concentrated market structure. The introduction of foreign Islamic banks caused the market structure to become more competitive and less concentrated by comparing the results that include foreign Islamic banks against the results generated with a subsample of domestic Islamic banks only. Bank Negara Malaysia’s (BNM’s) financial reform and the liberalisation of the financial system were proven to induce competition making the financial system more resilient, competitive and dynamic. The Islamic banks have recorded consistently increased annual performance with the under-performing Islamic banks catching up on the top performers.

Originality/value
Very few research studies have focused on the market structure and competition of the Islamic banking industry in Malaysia, especially using recent financial data; this study will contribute to filling the existing gap.
Social disclosure: compliance of Islamic banks to governance standards No. 7 of AAOIFI (2010)
Authors: Brahim Nouha Ben , Arab Mounira Ben 
Published: February 2020

Purpose
This paper aims to investigate the compliance of Islamic banks (IBs) with the AAOIFI standard No. 7, in Middle East and North Africa area during the period 2010-2014. The authors seek to identify, among the 15 countries and 72 banks, those which conform more to this standard. The level of compliance is expected to be more stringent in countries where AAOIFI standards are made mandatory.

Design/methodology/approach
The paper uses the unweighted disclosure method which measures the corporate social report disclosure (CSRD) score of a bank as additive. Each country and bank are assessed according to two obligatory and voluntary CSRDs.

Findings
The empirical results indicate that even though the global disclosure index has been improved over the observation period, it has remained relatively low. The results also allowed us to see that the global, mandatory and voluntary societal disclosures vary according to the country and banks. Further, it has been seen that banks allow more attention to the mandatory disclosure recommendations of AAOIFI Governance Standard No. 7, in comparison with the voluntary CSRD.

Research limitations/implications
One limitation of this study is that the sample is restricted to only the Islamic banking sector. Future research could include other Islamic financial institutions (IFIs) such as insurance companies. Second, the study could be extended to other countries to better control the religious system and cultural effects. Because in our modern era, traditional laws in the Muslim world have been widely replaced by statutes inspired by European models, the authors suggest then to apply a new classification that separates, for instance, countries that rely on an Islamic model from those with a western model, and national banks from those allied with western banks. Finally, the paper’s data collection relies solely on annual reports and does not include publications from bank sites. Future research could consider all these limitations. Another possible avenue could examine the determinants of such disclosure level.

Practical implications
Almost no study has been limited to the text of the AOIFFI. This detail is important for some countries where the AAOIFI standards are mandatory.

Social implications
The findings may be of interest to shareholders and all those who deal with IBs that have religious expectations.

Originality/value
Despite the fact that most studies investigated compliance of IB Sharia law, almost no study has been limited to the text of the AOIFFI. This detail is important for some countries where the AAOIFI standards are mandatory. The findings may be of interest to shareholders and all those who deal with IBs that have religious expectations.