bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Associations of Interleukin 6 Receptor Variant Across Genetic Ancestries and Implications for Targeted Therapies
Authors: Wang Xuan , Nogues Isabelle-Emmanuella , Liu Molei , Chen Tony , Xiong Xin , Bonzel Clara-Lea , Zhang Harrison , Hong Chuan , Dahal Kumar , Costa Lauren , Gaziano J. Michael , Kim Seoyoung C. , Ho Yuk-Lam , Cho Kelly , Cai Tianxi , Liao Katherine P. 
Published: September 2022

AbstractGenomic data are increasingly incorporated into high-throughput approaches such as the Phenome-Wide Association Study (PheWAS) to query potential effects of targeted therapies. Genetic variants, such as the interleukin-6 receptor (IL6R) genetic variant rs2228145 (Asp358Ala), have been identified with a downstream effect similar to the drug, e.g., tocilizumab which targets IL6R, and can be used to screen for potential protective or harmful signal across a broad range of traits in large biobanks with linked genomic and clinical data. To date, there are limited approaches to determine whether these effects may differ across diverse populations to inform potential differential drug effects especially in populations under-represented in clinical trials. In this study, we developed and applied an approach to detect heterogeneous associations, using the IL6R variant as an example, in African vs European ancestry. We identified a total of 29 traits with a differential association between the IL6R variant, with notable differences including a lower risk of type 2 diabetes in AFR vs EUR, and a higher white blood cell count. With the increasing use of targeted blockade of the IL6 pathway in conditions ranging from rheumatologic to cardiovascular conditions, the findings from this study can inform ongoing studies targeting IL6; general approach to test for heterogeneity of associations can be applied broadly to any PheWAS.
SAGA histone acetyltransferase module facilitates chromatin accessibility to SMC5/6
Authors: Mahrik L. , Stefanovie B. , Maresova A. , Princova J. , Kolesar P. , Lelkes E. , Helmlinger D. , Prevorovsky M. , Palecek J.J. 
Published: September 2022

AbstractStructural Maintenance of Chromosomes (SMC) complexes are molecular machines driving chromatin organization at higher levels. In eukaryotes, three SMC complexes (cohesin, condensin, and SMC5/6) play key roles in cohesion, condensation, replication, transcription and DNA repair. Here, we performed a genetic screen in fission yeast to identify novel factors required for SMC5/6 binding to DNA. We identified 79 genes of which histone acetyltransferases (HATs) were the most represented. Genetic and phenotypic analyses suggested a particularly strong functional relationship between the SMC5/6 and SAGA complexes. Furthermore, several SMC5/6 subunits physically interacted with SAGA HAT module components Gcn5 and Ada2. As Gcn5-dependent acetylation facilitates the accessibility of chromatin to DNA repair proteins, we first analysed the formation of DNA damage-induced SMC5/6 foci in the Δgcn5mutant. The SMC5/6 foci formed normally in Δgcn5, suggesting SAGA-independent SMC5/6 localization to DNA-damaged sites. Next, we used Nse4-FLAG chromatin-immunoprecipitation (ChIP-seq) analysis in unchallenged cells to assess SMC5/6 distribution. A significant portion of SMC5/6 accumulated within gene regions in wild-type cells, which was reduced in Δgcn5and Δada2mutants. The drop in SMC5/6 levels was also observed ingcn5-E191Q acetyltransferase-dead mutant. Altogether, our data suggest that the SAGA HAT module may facilitate chromatin accessibility to SMC5/6 at gene regions.Author SummaryGenomes of all eukaryotes must be folded and packed into their relatively small nuclear spaces. Histones first pack free genomic DNA into nucleosomes and their arrays. Other complexes like histone modifiers and remodelers can regulate nucleosome positions and their packing within chromatin fibres. They assist in the relative opening or condensation of chromatin fibres and facilitate their accessibility to DNA-binding proteins. The highly conserved Structural Maintenance of Chromosomes (SMC) complexes (cohesin, condensin, and SMC5/6) compact further chromatin fibres at higher levels. These molecular machines can loop chromatin fibres, which need access to segments of free DNA for their physical binding to DNA. Here, we studied genetic and physical interactions between histone-modifying SAGA complex and SMC5/6. We show that the SAGA histone acetyltransferase module may facilitate chromatin access to SMC5/6.
RGA1 alleviates low-light-repressed pollen tube growth by improving the metabolism and allocation of sugars and energy
Authors: Li (李沪波) Hubo , Feng (奉保华) Baohua , Li (李俊材) Juncai , Fu (符卫蒙) Weimeng , Wang (王文婷) Wenting , Chen (陈婷婷) Tingting , Liu (刘连盟) Lianmeng , Wu (武志海) Zhihai , Peng (彭少兵) Shaobing , Tao (陶龙兴) Longxing , Fu (符冠富) Guanfu 
Published: September 2022

AbstractLow-light stress compromises photosynthetic and energy efficiency and leads to spikelet sterility; however, the effect of low-light stress on pollen tube elongation in the pistil remains poorly understood. The gene RGA1, which encodes a Gα subunit of the heterotrimeric G protein, enhanced low-light tolerance in rice plants at anthesis by preventing the cessation of pollen tube elongation in the pistil. The levels of reactive oxygen species were higher and the content of ATP and ATPase was lower in RGA1 mutant (d1) plants compared with wild-type and RGA1-overexpressing (OE-1) plants under low-light conditions. Energy deficits, rather than interference with signaling transduction pathways, were the main contributors to the inhibition of pollen tube elongation in the pistil by low-light stress. In this process, marked increases in the activities of acid invertase (INV), sucrose synthase (SUS), and mitochondrial respiratory electron transport chain complexes, as well as the relative expression levels of SUTs, SWEETs, SUSs, INVs, CINs, SnRK1A, and SnRk1B, were observed in OE-1 plants. INV and ATPase activators (sucrose and Na2SO3, respectively) increased spikelet fertility by improving the energy status in the pistil under low-light conditions, and the ATPase inhibitor Na2VO4 induced spikelet sterility and decreased ATPase activity. Therefore, RGA1 could alleviate the low-light stress-induced impairment of pollen tube elongation to increase spikelet fertility by promoting sucrose unloading in the pistil and improving the metabolism and allocation of energy.
The genomes of medicinal skullcaps reveal the polyphyletic origins of clerodane diterpene biosynthesis in the family Lamiaceae
Authors: Li Haixiu , Wu Song , Lin Ruoxi , Xiao Yiren , Malaco Morotti Ana Luisa , Wang Ya , Huang Tao , Zhao Yong , Zhou Xun , Yang Jun , Zhao Qing , Kanellis Angelos K. , Martin Cathie , Tatsis Evangelos C. 
Published: September 2022

AbstractThe presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata, although the molecular mechanisms behind clerodane biosynthesis are unknown. Here, we report a high-quality assembly of the 414.98 Mb genome of S. barbata into thirteen pseudochromosomes. Using phylogenomic and biochemical data, we mapped the plastidial metabolism of kaurene (gibberellins), abietane and clerodane diterpenes in three species of the family Lamiaceae (Scutellaria barbata, Scutellaria baicalensis and Salvia splendens), facilitating the identification of genes involved in the biosynthesis of the clerodanes, kolavenol and isokolavenol. We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism. Despite the assumed monophyletic origin of clerodane biosynthesis which is widespread in species of the Lamiaceae, our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae. Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the elucidation of anticancer clerodanes biosynthesis and future metabolic engineering efforts to increase the production of these high-value chemicals.
NBS1 binds directly to TOPBP1 via disparate interactions between the NBS1 BRCT1 domain and the TOPBP1 BRCT1 and BRCT2 domains
Authors: Huynh Oanh , Ruis Kenna , Montales Katrina , Michael W. Matthew 
Published: September 2022

AbstractThe TOPBP1 and NBS1 proteins are key components of DNA repair and DNA-based signaling systems. TOPBP1 is a multi-BRCT domain containing protein that plays important roles in checkpoint signaling, DNA replication, and DNA repair. Likewise, NBS1, which is a component of the MRE11-RAD50-NBS1 (MRN) complex, functions in both checkpoint signaling and DNA repair. NBS1 also contains BRCT domains, and previous works have shown that TOPBP1 and NBS1 interact with one another. In this work we examine the interaction between TOPBP1 and NBS1 in detail. We report that NBS1 uses its BRCT1 domain to interact with TOPBP1’s BRCT1 domain and, separately, with TOPBP1’s BRCT2 domain. Thus, NBS1 can make two distinct contacts with TOPBP1. We report that recombinant TOPBP1 and NBS1 proteins bind one another in a purified system, showing that the interaction is direct and does not require post-translational modifications. Surprisingly, we also report that intact BRCT domains are not required for these interactions, as truncated versions of the domains are sufficient to confer binding. For TOPBP1, we find that small 24-29 amino acid sequences within BRCT1 or BRCT2 allow binding to NBS1, in a transferrable manner. These data expand our knowledge of how the crucial DNA damage response proteins TOPBP1 and NBS1 interact with one another and set the stage for functional analysis of the two disparate binding sites for NBS1 on TOPBP1.
Aging and Obesity Prime the Methylome and Transcriptome of Adipose Stem Cells for Disease and Dysfunction
Authors: Xie Shaojun , Choudhari Sulbha , Wu Chia-Lung , Abramson Karen , Corcoran David , Gregory Simon G. , Thimmapurum Jyothi , Guilak Farshid , Little Dianne 
Published: September 2022

AbstractThe epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12- months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to the effects of age, but this was not true in obese mice. Functional pathway analyses identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. Specifically,Mapt, Nr3c2, App, and Ctnnb1emerged as potential hypomethylated upstream regulators in both aging and obesity (AL vs YL and AO vs YO), andApp,Ctnnb1, Hipk2, Id2,andTp53exhibited additional effects of aging in obese animals. Further,Foxo3andCcnd1were potential hypermethylated upstream regulators of healthy aging (AL vs YL), and of the effects of obesity in young animals (YO vs YL), suggesting that these factors could play a role in accelerated aging with obesity. Finally, we identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Further mechanistic studies are needed to validate the roles of these genes capable of priming ASCs for dysfunction in aging- and obesity-associated pathologies.
Pandemic silver lining: how the COVID-19 pandemic helped women to beat the “gender stereotypes pandemic” in entrepreneurship
Authors: Muzaffar Haroon 
Published: September 2022

Purpose
This study aims to explore how the COVID-induced exogenous shock changed the prevalent occupational gender stereotypes in entrepreneurship in urban Turkey and presented an opportunity to some Turkish women to start their own business. Furthermore, this study investigated how women entrepreneurs’ social networks helped them to clear the gendered hurdles that hindered their entrepreneurial endeavors in the times of COVID-19.

Design/methodology/approach
Highly personal topics like gender stereotypes are complex and nebulous, as is entrepreneurship as lived experience. Moreover, the COVID-induced crisis complicates the context further, which is why the addressal of questions about gendered stereotypes in the process of entrepreneurship, and the role of social networks in that process, warrants a qualitative research approach. Consequently, this study relied on in-depth semistructured interviews for investigating the study’s research questions.

Findings
The findings suggest that research participants used the COVID-induced crisis conditions as an opportunity to beat the existing occupational gender stereotyping in entrepreneurship in the context of urban Turkey that opened a window of opportunity for the women participants to enter into entrepreneurship. In addition, social networks significantly helped the women entrepreneurs to acquire resources, and provided the leverage needed to clear the gendered hurdles that hindered the women’s entrepreneurial endeavors.

Originality/value
To the best of the author’s knowledge, this study is among the first that generates insights into occupational gender stereotyping in entrepreneurship within the context of a developing country in the times of COVID-19 crisis. Hence, this study can help to understand the broader implications of the crisis like COVID-19 for gender-related beliefs and attitudes toward women entrepreneurship within the context of developing countries.
Memorable dining experiences amidst the COVID-19 pandemic
Authors: Ma Forest , DiPietro Robin B. , Li Jing , Harris Kimberly J. 
Published: September 2022

Purpose
This study aims to investigate the effects of memorable dining experiences (MDEs) in the USA during the COVID-19 pandemic.

Design/methodology/approach
A total of 530 valid survey responses were collected in the USA. Partial least squares structural equation modeling (PLS–SEM) was used to estimate inner and outer models. A two-stage approach was applied to test the moderating effects of restaurant safety measures. Additional analyses were conducted to compare electronic word of mouth (eWOM) intention and actual eWOM behavior.

Findings
All five dimensions contributed to the overall memorability of a dining experience, with affect being the primary factor. Overall memorability was positively related to subjective well-being and actual eWOM behavior. Restaurant safety measures were positively related to the overall experience but did not moderate the relationship between any dimension and overall memorability.

Research limitations/implications
Findings provide empirical support for the conceptualization of MDEs during a pandemic and underscore the importance of actual eWOM behavior in restaurant research.

Practical implications
Results offer guidance for restaurant managers in designing MDEs.

Originality/value
The restaurant industry is evolving from simply providing products and services to creating experiences. Yet the impacts of crafting MDEs are not well understood, especially during a pandemic. This study filled this gap by investigating MDEs and their effects on subjective well-being and eWOM behavior.
Resilience in hospitality and tourism: issues, synthesis and agenda
Authors: Hall C. Michael , Safonov Alexander , Naderi Koupaei Sarah 
Published: September 2022

PurposeThis paper aims to identify research approaches and issues in relation to the main paradigms of resilience: engineering resilience, ecological resilience and socio-ecological resilience. This paper provides a synthesis of the core elements of each resilience approach and their implications.Design/methodology/approachA critical thematic review was undertaken of the hospitality and tourism resilience literature.FindingsResilience is a contested boundary object with different understandings according to conceptual and disciplinary position. The dominant approach in hospitality and tourism studies is primarily informed by engineering resilience with the focus at the organizational level. The ontological and epistemological understanding of resilience and change concepts appears limited leading to a lack of appreciation of the multi-scaled nature of resilience and the importance of slow change.Research/limitations/implicationsThe research has important implications for understanding the key elements of different approaches to resilience.Practical implicationsThe research synthesis may help improve resilience strategy and policymaking, including indicator selection.Social implicationsThe research notes the relationship of resilience to sustainability, the potential for learning and decision-making practices.Originality/valueIn addition to thematic analysis, a model of the multi-scaled nature of resilience is provided and the key elements of the three main approaches with implications for theory and practice.
Digital onboarding and employee outcomes: empirical evidence from the UK
Authors: Sani Kareem Folohunso , Adisa Toyin Ajibade , Adekoya Olatunji David , Oruh Emeka Smart 
Published: September 2022

PurposeGiven the sharp rise in the adoption of digital onboarding in employment relations and human resource management practices, largely caused by the continuing COVID-19 pandemic, this study explores the impact of digital onboarding on employees' wellbeing, engagement level, performance, and overall outcomes.Design/methodology/approachThis study uses an interpretive qualitative research methodology, undertaking semi-structured interviews with 28 participants working in the UK services industry.FindingsThe study finds that digital onboarding has a significant impact on employee outcomes, following the perceptions of “dwindling social connectedness and personal wellbeing”, “meaningful and meaningless work”, and “poor employee relations” among employees and their employers in the workplace.Practical implicationsDue to the increased adoption of digital onboarding, human resources teams must focus on having considerable human interaction with new hires, even if this means adopting a hybrid approach to onboarding. Human resources teams must ensure that they work together with line managers to promote a welcoming culture for new hires and facilitate organisation-driven socialisation tactics and the “quality” information necessary for supporting new employees. For new employees, besides acquiring the digital skills that are essential in the workplace, they must accept the changing digital landscape in order to practice effective communication and align their goals and values with those of their organisation.Originality/valueQualitative research on the influence of digital onboarding on employee outcomes is limited, with much of the research yet to substantially consider the impact of digitalisation on the human resources function of onboarding employees as full members of an organisation.
How do functional traits influence tree demographic properties in a subtropical monsoon forest?
Authors: He Pengcheng , Lian Juyu , Ye Qing , Liu Hui , Zheng Yi , Yu Kailiang , Zhu Shidan , Li Ronghua , Yin Deyi , Ye Wanhui , Wright Ian J. 
Published: September 2022

Abstract

Functional traits are good predictors of plant responses and adaptations to ever‐changing environments. However, forecasting forest community dynamics is challenging because the relationships among different tree demographic properties (growth, mortality and recruitment) and how functional traits are associated with tree demography remain largely unknown.

Here, in a 20‐ha subtropical forest permanent plot, we quantified the rates of tree growth, mortality and recruitment across 53 dominant tree species (diameter at breast height; DBH ≥ 1 cm) from 2005 to 2020. Functional traits that are closely related to plant photosynthesis, nutrients, hydraulics and drought tolerance were measured.

We found that tree growth rate (GR) varied independently from rates of tree mortality and recruitment. Hydraulic conductivity was positively correlated with GR (explaining 27% variation—the strongest relationship observed) whereas wood density was negatively correlated with GR. Leaf life span was negatively related to tree mortality. Species with high carbon assimilation rate, nutrient concentration and hydraulic conductivity had high recruitment rates. Leaf turgor loss point was unrelated to plant demography. Principal component analysis revealed that species with quick resource acquisition rates had high rates of growth and recruitment.

Our results illustrate that the correlations among tree demographic properties were weak in this subtropical forest with monsoonal climate. Most notably, against expectations, there was no observed trade‐off between growth and mortality. Individual functional traits explained up to 27% of each demographic rate. Variation in recruitment rate was aligned with traits indexing the leaf economic spectrum and also plant hydraulic variation. A better understanding of the role of disturbances on trait–demography relationships would help build a deeper and more nuanced understanding of the ecology of subtropical monsoon forests.

Read the free Plain Language Summary for this article on the Journal blog.
Maternal sudden death: A nationwide retrospective study
Authors: Braund Sophia , Leviel Juliette , Morau Estelle , Deneux‐Tharaux Catherine , Verspyck Eric ,   ENCMM study group
Published: September 2022

AbstractObjectiveTo determine the prevalence of maternal sudden death (MSD) and to compare the characteristics of death between women with explained and unexplained sudden death.DesignA national retrospective study in France.PopulationMaternal deaths related to an unexpected sudden cardiac arrest were extracted from the French National Confidential Enquiry into Maternal Deaths database for 2007–2012.MethodsMaternal, pregnancy, sudden death characteristics and maternal investigations were compared between women with explained and unexplained cause of death.ResultsA total of 83 maternal sudden deaths and 4 949 890 live births occurred over the period studied, thus accounting for 16% of all maternal deaths (n = 510). Death was explained in 51 (61%) women and unexplained in 32 women (39%). Compared with women with unexplained death, women with explained death were more often found to have in‐hospital cardiac arrest (47% versus 12%, P < 0.01), witnessed cardiac arrest (86% versus 62%, P = 0.03) and in‐hospital death (82% versus 47%, P < 0.01). Postmortem investigations such as autopsy and/or CT scan (65% versus 31%, P < 0.01) were also more often carried out in women with explained death. The proportion of deaths for which the preventability factors could not be assessed was 58% among unexplained MSD and 7% among explained MSD.ConclusionMaternal sudden death is a rare event but accounts for a high proportion of all maternal deaths. This highlights the importance of providing training in diagnostic and management strategy for care providers. Systematic postmortem investigations are required to help understand causes and improve practices.