bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructing human early embryogenesis in vitro with pluripotent stem cells
Authors: Sozen Berna , Jorgensen Victoria , Zhu Meng , Cui Tongtong , Zernicka-Goetz Magdalena 
Published: March 2021

ABSTRACTUnderstanding human development is of fundamental biological and clinical importance. Yet despite its significance, insights into early developmental events in humans still remain largely unknown. While recent advances show that stem cells can mimic embryogenesis1–9to unravel hidden developmental mechanisms, a stem cell-based model of early human embryogenesis is lacking. Here, we use human extended pluripotent stem cells10to reconstitute early human development in 3-dimensions and recapitulate early embryo-like events. We first perform a systematic characterisation to reveal unique signalling requirements for building the human pre-implantation blastocyst. Further, we show that thesein vitrostem cell-derived blastocyst-like structures are able to undertake spatiotemporal self-organisation to mimic peri-implantation remodelling in which a polarised rosette opens up the amniotic cavity within a developing disc. The hallmarks of human early development displayed by this stem cell-basedin vitromodel mimics features of embryonic day 3 to day 9/10 of natural development. Thus, this platform represents a tractable model system to contribute to the basic understanding of cellular and molecular mechanisms governing early embryonic events in humans and to provide valuable insights into the design of differentiation protocols for human stem cells in clinical applications.
TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins
Authors: Levine Tim P. 
Published: March 2021

AbstractTMEM106B is an integral membrane protein of late endosomes and lysosomes involved in neuronal function, its over-expression being associated with familial frontotemporal lobar degeneration, and under-expression linked to hypomyelination. It has also been identified in multiple screens for host proteins required for productive SARS-CoV2 infection. Because standard approaches to understand TMEM106B at the sequence level find no homology to other proteins, it has remained a protein of unknown function. Here, the standard tool PSI-BLAST was used in a non-standard way to show that the lumenal portion of TMEM106B is a member of the LEA-2 domain superfamily. The non-standard tools (HMMER, HHpred and trRosetta) extended this to predict two yeast LEA-2 proteins in the lumenal domains of the degradative vacuole, equivalent to the lysosome: one in Vac7, a regulator of PI(3,5)P2production, and three in Tag1 which signals to terminate autophagy. Further analysis of previously unreported LEA-2 structures indicated that LEA-2 domains have a long, conserved lipid binding groove. This implies that TMEM106B, Vac7 and Tag1 may all be lipid transfer proteins in the lumen of late endocytic organelles.
Experience-related remapping of temporal encoding by striatal ensembles
Authors: Bruce R. Austin. , Weber Matthew A. , Volkman Rachael A. , Oya Mayu , Emmons Eric B. , Kim Youngcho , Narayanan Nandakumar S. 
Published: March 2021

AbstractTemporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson’s disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium-spiny neurons (MSNs) in the dorsal striatum of mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to “switch” response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time-related ramping activity and response-related activity increased with more experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time-related ramping activity. Finally, we found that some MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.
Antimalarials in mosquitoes overcomeAnophelesandPlasmodiumresistance to malaria control strategies
Authors: Paton Douglas G. , Probst Alexandra S. , Ma Erica , Adams Kelsey L. , Shaw W. Robert , Singh Naresh , Bopp Selina , Volkman Sarah K. , Hien Domombele F. S. , Paré Prislaure S. L. , Yerbanga Rakiswendé S. , Diabaté Abdoullaye , Dabiré Roch K. , Lefèvre Thierry , Wirth Dyann F. , Catteruccia Flaminia 
Published: March 2021

AbstractThe spread of insecticide resistance inAnophelesmosquitoes and drug resistance inPlasmodiumparasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these issues an urgent public health priority. We recently showed that the transmission ofPlasmodium falciparumparasites can be efficiently blocked when exposingAnopheles gambiaefemales to antimalarials deposited on a treated surface, with no negative consequences on mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistantAnophelesare exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistantP. falciparumparasites (Kelch13C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.Significance StatementEffective control of malaria is hampered by resistance to vector-targeted insecticides and parasite-targeted drugs. This situation is exacerbated by a critical lack of chemical diversity in both interventions and, as such, new interventions are badly needed. Recent laboratory studies have shown that an alternative approach based on treatingAnophelesmosquitoes directly with antimalarial compounds can render the vector incapable of transmitting thePlasmodiumparasites that cause malaria. While promising, showing that mosquito-targeted antimalarials remain effective against wild parasites and mosquitoes, including drug- and insecticide-resistant populations, respectively, is crucial to the future viability of this approach. In this study, carried out in the US and Burkina Faso, we show that antimalarial exposure is highly effective, even against extremely resistant mosquitoes, and can block transmission of drug-resistant parasites. By combining lab, and field-based studies in this way we have demonstrated that this novel approach can be effective in areas where conventional control measures are no longer as effective.
Massively parallel reporter perturbation assay uncovers temporal regulatory architecture during neural differentiation
Authors: Kreimer Anat , Ashuach Tal , Inoue Fumitaka , Khodaverdian Alex , Yosef Nir , Ahituv Nadav 
Published: March 2021

AbstractGene regulatory elements play a key role in orchestrating gene expression during cellular differentiation, but what determines their function over time remains largely unknown. Here, we performed perturbation-based massively parallel reporter assays at seven early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide cellular differentiation. By perturbing over 2,000 putative DNA binding motifs in active regulatory regions, we delineated four categories of functional elements, and observed that activity direction is mostly determined by the sequence itself, while the magnitude of effect depends on the cellular environment. We also find that fine-tuning transcription rates is often achieved by a combined activity of adjacent activating and repressing elements. Our work provides a blueprint for the sequence components needed to induce different transcriptional patterns in general and specifically during neural differentiation.
An Off-the-Shelf Bioadhesive Patch for Sutureless Repair of Gastrointestinal Defects
Authors: Wu Jingjing , Yuk Hyunwoo , Sarrafian Tiffany L. , Guo Chuanfei , Griffiths Leigh G. , Nabzdyk Christoph S. , Zhao Xuanhe 
Published: March 2021

ABSTRACTSurgical sealing and repair of injured and resected gastrointestinal (GI) organs are critical requirements for successful treatment and tissue healing. Despite being the standard of care, hand-sewn closure of GI defects using sutures faces various limitations and challenges. The process remains technically complicated and time-consuming. The needle-piercing and pointwise closure also inflict tissue damage and stress concentration, raising the risk of local failure and subsequent anastomotic leaks. To address these limitations and challenges, we introduce an off-the-shelf bioadhesive GI patch capable of atraumatic, rapid, robust, and sutureless repair of GI defects. The GI patch synergistically integrates a non-adhesive top layer and a dry bioadhesive bottom layer, resulting in a thin, flexible, transparent, and ready to use dressing with tissue-matching mechanical properties. Rapid, robust, and sutureless sealing capability of the GI patch is systematically characterized based on various standard tests inex vivoporcine GI organ models.In vitroandin vivorat models are utilized to validate biocompatibility and biodegradability of the GI patch including comprehensive cytotoxicity, histopathology, immunofluorescence, and blood analyses. To validate the GI patch’s efficacy in a clinically relevant setting, we demonstrate successful suturelessin vivosealing and healing of GI defects; namely in rat stomach and colon, and porcine colon injury models. The proposed GI patch not only provides a promising alternative to suture for repair of GI defects but also offers potential clinical opportunities in the treatment and repair of other organs.One Sentence SummaryAn off-the-shelf bioadhesive patch is introduced for facile sutureless repair of gastrointestinal defects, addressing various limitations of conventional suture-based treatments.
Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by CDS composition and mRNA localisation
Authors: Gillen Sarah L. , Giacomelli Chiara , Hodge Kelly , Zanivan Sara , Bushell Martin , Wilczynska Ania 
Published: March 2021

AbstractBackgroundRegulation of protein output at the level of translation allows for a rapid adaptation to dynamic changes to the cell’s requirements. This precise control of gene expression is achieved by complex and interlinked biochemical processes that modulate both the protein synthesis rate and stability of each individual mRNA. A major factor coordinating this regulation is the Ccr4-Not complex. Despite playing a role in most stages of the mRNA life cycle, no attempt has been made to take a global integrated view of how the Ccr4-Not complex affects gene expression.ResultsThis study has taken a comprehensive approach to investigate post-transcriptional regulation mediated by the Ccr4-Not complex assessing steady-state mRNA levels, ribosome position, mRNA stability and protein production transcriptome-wide. Depletion of the scaffold protein CNOT1 results in a global upregulation of mRNA stability and the preferential stabilisation of mRNAs enriched for G/C-ending codons. We also uncover that mRNAs targeted to the ER for their translation have reduced translational efficiency when CNOT1 is depleted, specifically downstream of the signal sequence cleavage site. In contrast, translationally upregulated mRNAs are normally localised in p-bodies, contain disorder-promoting amino acids and encode nuclear localised proteins. Finally, we identify ribosome pause sites that are resolved or induced by the depletion of CNOT1.ConclusionWe define the key mRNA features that determine how the human Ccr4-Not complex differentially regulates mRNA fate and protein synthesis through a mechanism linked to codon composition, amino acid usage, and mRNA localisation.
Stigma hurts: exploring employer and employee perceptions of tattoos and body piercings in Nigeria
Authors: Adisa Toyin Ajibade , Adekoya Olatunji David , Sani Kareem Folohunso 
Published: March 2021

PurposeThis study draws on social stigma and prejudice to examine the perceptions and beliefs of managers and employees regarding visible tattoos and body piercings, as well as the impact they have on potential employment and human resource management in the global South, using Nigeria as the research context.Design/methodology/approachThe study uses a qualitative research approach, drawing on data from 43 semi-structured interviews with employees and managers in Nigeria.FindingsContrary to the popular opinion that tattoos and body piercings are becoming more accepted and mainstream in society, this study finds that some Nigerian employers and employees may stigmatise and discriminate against people with visible tattoos and body piercings. The findings of this study suggest that beliefs about tattoos are predicated on ideologies as well as religious and sociocultural values, which then influence corporate values.Research limitations/implicationsThe extent to which the findings of this research can be generalised is constrained by the limited sample and scope of the research.Practical implicationsReligious and sociocultural preconceptions about people with visible tattoos and body piercings have negative implications for the recruitment and employment of such people and could prevent organisations from hiring and keeping talented employees. This implies that talented employees might experience prejudice at job interviews, preventing them from gaining employment. Furthermore, stigmatising and discriminating against people with visible tattoos and body piercings may lead to the termination of employment of talented employees, which could negatively affect organisational productivity and growth.Originality/valueThis study provides an insight into the employment relations regarding tattoos and body piercing in Nigeria. The study highlights the need for mild beliefs and positive perceptions about people with visible tattoos and unconventional body piercings. There should be a general tolerance of the individual preference for body art and physical appearance, and this tolerance should be incorporated in organisational policies, which are enactments of corporate culture.
CMS at 13: a retrospective of the journey
Authors: Farrukh Muhammad , Raza Ali , Meng Fanchen , Wu Yihua 
Published: March 2021

Purpose
To commemorate the 13th anniversary of the Chinese Management Studies (CMS) and suggest future research directions, this study aims to present an overview of the CMS through a systematic bibliometric analysis from 2007 to 2019. The analysis emphasizes the trend of themes, structure of publications and citations, the most cited publications, the most productive authors, universities, countries and regions.

Design/methodology/approach
The study uses the data extracted from the Scopus database to present an overview; besides, it also uses VOSviewer and Bibliometrix software packages to visualize the intellectual network of CMS.

Findings
This analysis is based on 486 publications between 2007 and 2019. Results show that there is a rising trend in the number of citations to CMS. The researchers from China were the most frequent contributors to the journal, whereas researchers from the USA, Taiwan, Singapore and Australia were well represented. In addition, the results show that innovation, leadership, human resource management and corporate social responsibility have been the most important research themes in the journal.

Practical implications
This study offers an objective view of the CMS publication structure. The study’s findings can help the journal readers obtain a quick snapshot of the leading trends occurring in the journal. Furthermore, this study provides future research directions for the journals by underscoring important themes.

Originality/value
As the journal’s first retrospective, this study not only educates and enriches CMS’ global readers and aspiring contributors but can also be useful to its editorial board, as it provides several inputs in the form of future research directions to guide the journal’s progress.
Restaurant failure in post-conflict Beirut: the macroenvironmental context and mismanagement
Authors: Yacoub Laurent , Nakhle Samer , Yahiaoui Dorra 
Published: March 2021

PurposeGiven the complexity of a post-conflict environment, the restaurant sector needs to be analyzed not just from the economic perspective. This paper aims to identify the diverse macroenvironmental and managerial factors underlying restaurant failures in Lebanon. The authors hope that this effort may help increasing restaurant success rates in other post-conflict settings.Design/methodology/approachThe aim of this paper is to explain how macroenvironmental pressures influence the restaurant business and which managerial factors are most critical in a post-conflict context. The authors adopted a qualitative method by conducting face-to-face, semi-structured interviews.FindingsThe findings show that restaurant failures in a competitive and uncertain post-conflict environment were caused mainly by a snowball of internal organizational factors related to bad management, poor human resource management policies, inefficiency and fraud. Internal organizational factors can all be associated with human mistakes and bad decisions, including excessive initial investment, expensive decoration, inability to manage monthly expenses, bad communication and market research.Originality/valueThis study contributes to the literature regarding restaurant failures in post-conflict regions and presents results that are expected to help managers in family- and non-family-owned businesses to enhance their decision-making process.
Examination of impact of COVID-19 on stock market: evidence from American peninsula
Authors: Amin Ali , Arshad Muhammad , Sultana Naheed , Raoof Rabeeya 
Published: March 2021

PurposeThe rapid spread of COVID-19 has dramatic effects on financial market across the globe. This study analyzes the relationship between the COVID-19 cases, age and stock market indexes in Central America, North America, and South America.Design/methodology/approachThe panel regression analysis on three regions from March 10, 2020 to April 9, 2020 was conducted to test the hypothesized model. The authors used Levin et al.’s (2002) panel data unit root test to check the stationarity, and Hausman (1978) test was applied to determine the random and fixed effects.FindingsThe authors’ panel regression results indicate that the COVID-19 cases have a negative impact on stock indexes, whereas the age has a positive impact on the stock indexes. The region-wise analysis supports the panel finding except for South America, which shows an insignificant association between stock indexes and COVID-19 cases.Originality/valueThe study supplements the literature by examining the impact of pandemics on stock indexes and focus on three multicultural regions, comprising developed, developing and emerging countries, which are hitherto unaddressed.
Mentoring and newcomer well-being: a socialization resources perspective
Authors: Cai Di , Liu Shengming , Liu Jia , Yao Li , Jia Xingze 
Published: March 2021

PurposeThe purpose of this paper is to examine the effect of mentoring on newcomer well-being, as mediated by newcomer socialization and moderated by proactive personality.Design/methodology/approachData were collected at four time points in a sample of 227 newcomers. Regression analysis and bootstrapping method were used to test the hypotheses.FindingsMentoring had a positive and indirect effect on newcomer well-being through socialization. The moderated mediation analysis also revealed that proactive personality augmented the direct effect of mentoring on socialization and its indirect effect on well-being.Research limitations/implicationsOur data were collected in China, thereby limiting the generalization of the research findings. Future research can test our model in different cultural contexts.Practical implicationsOrganizations should consider establishing a mentoring program to foster newcomer socialization and achieve well-being. Within the mentoring context, cultivating newcomers to become more proactive can predict higher socialization levels, resulting in higher well-being.Originality/valuePrevious research largely focused on the development of the well-being of tenured employees. Drawing on socialization resources theory, this study focuses on the newcomer well-being and proposes the influential mechanism and boundary condition of the relationship between mentoring and newcomer well-being. It sheds light on exploring the well-being development for newcomers.
A network case of knowledge brokering
Authors: Rodway Joelle , MacGregor Stephen , Daly Alan , Liou Yi-Hwa , Yonezawa Susan , Pollock Mica 
Published: March 2021

PurposeThe purpose of this paper is two-fold: (1) to offer a conceptual understanding of knowledge brokering from a sociometric point-of-view; and (2) to provide an empirical example of this conceptualization in an education context.Design/methodology/approachWe use social network theory and analysis tools to explore knowledge exchange patterns among a group of teachers, instructional coaches and administrators who are collectively seeking to build increased capacity for effective mathematics instruction. We propose the concept of network activity to measure direct and indirect knowledge brokerage through the use of degree and betweenness centrality measures. Further, we propose network utility—measured by tie multiplexity—as a second key component of effective knowledge brokering.FindingsOur findings suggest significant increases in both direct and indirect knowledge brokering activity across the network over time. Teachers, in particular, emerge as key knowledge brokers within this networked learning community. Importantly, there is also an increase in the number of resources exchanged through network relationships over time; the most active knowledge brokers in this social ecosystem are those individuals who are exchanging multiple forms of knowledge.Originality/valueThis study focuses on knowledge brokering as it presents itself in the relational patterns among educators within a social ecosystem. While it could be that formal organizational roles may encapsulate knowledge brokering across physical structures with an education system (e.g. between schools and central offices), these individuals are not necessarily the people who are most effectively brokering knowledge across actors within the broader social network.