bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous transcriptome and proteome profiling in a single mouse oocyte with a deep single-cell multi-omics approach
Authors: Jiang Yi-Rong , Zhu Le , Cao Lan-Rui , Wu Qiong , Chen Jian-Bo , Wang Yu , Wu Jie , Zhang Tian-Yu , Wang Zhao-Lun , Guan Zhi-Ying , Xu Qin-Qin , Fan Qian-Xi , Shi Shao-Wen , Wang Hui-Feng , Pan Jian-Zhang , Fu Xu-Dong , Wang Yong-Cheng , Fang Qun 
Published: August 2022

AbstractNowadays, although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing and mass spectrometry technology, to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level for the first time. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19948 genes and 2663 protein groups in single mouse oocytes. This reliable quantitative two-omics dataset of single cells provided an important resource for understanding the relationship between the transcriptome and the proteome in cells. Based on the correlation analysis of RNAs and proteins in the same single cell, we demonstrated the expressive heterogeneity of transcriptome and proteome during the cellular biological process. Specially, we analyzed the meiosis regulatory network during oocyte maturation with an unprecedented depth at the single-cell level, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, providing crucial insights into the regulatory features of transcription and translation during oocyte meiotic maturation.
Identification of divergent botulinum neurotoxin homologs in Paeniclostridium ghonii
Authors: Wei Xin , Wentz Travis , Lobb Briallen , Mansfield Michael , Zhen William , Tan Huagang , Wu Zijing , Pellett Sabine , Dong Min , Doxey Andrew C. 
Published: August 2022

AbstractBotulinum neurotoxins (BoNTs) are the most potent family of toxins known to science. Bioinformatic studies in recent years have revealed that they are members of a broader toxin family, with an increasing number of divergent homologs identified in genomes of organisms outside of the Clostridium genus. Here, we report the identification of two putative divergent BoNT-like homologs in the genomes of two strains of Paeniclostridium ghonii. We designated them PG-toxin 1 (PGT1) and PG-toxin 2 (PGT2), which share ~54% protein sequence identity. Unlike any other known BoNT homologs, PGT1 and PGT2 are composed of two separate subunits encoded on two neighboring genes: one encoding the protease domain (light chain, LC) with a conserved HExxH motif, and the second encoding the heavy-chain (HC) containing the putative translocation domain and receptor-binding domain. Phylogenetic analysis of both the LC and HC reveal that it is a divergent member of the lineage of BoNT that also includes BoNT/X, BoNT/En and the insecticidal PMP1. The gene clusters harboring PGT1 and PGT2 also include a putative insecticidal delta-endotoxin, Cry8Ea1, as well as putative endolysin and bacteriocin genes that may facilitate lytic toxin secretion, suggesting a possibility that this gene cluster might serve an insecticidal purpose.
The origin of internal genes contributes to the replication and transmission fitness of H7N9 avian influenza virus
Authors: James Joe , Bhat Sushant , Walsh Sarah K. , K. Karunarathna H. M. Thusitha. , Sadeyen Jean-Remy , Chang Pengxiang , Sealy Joshua E. , Mahmood Sahar , Mollett Benjamin C. , Slomka Marek J. , Brookes Sharon M. , Iqbal Munir 
Published: August 2022

AbstractH9N2 avian influenza viruses (AIVs) have donated internal gene segments during the emergence of zoonotic AIVs, including H7N9. We used reverse genetics to generate three reassortant viruses (2:6 H7N9) which contained the Haemagglutinin and Neuraminidase from Anhui/13 (H7N9) and the six internal gene segments from H9N2 AIVs of G1-like or BJ94-like lineages enzootic in different geographic regions in Asia. Infection of chickens with the 2:6 H7N9 containing internal gene segments from G1-like H9N2 conferred attenuation in vivo, with lower shedding and reduced transmission to contact chickens. However, possession of BJ94-like H9N2 internal gene segments resulted in more rapid transmission and significantly elevated cloacal shedding compared to the parental Anhui/13 H7N9. In vitro analysis also showed that the 2:6 H7N9 having BJ94-like internal genes had significantly increased replication compared to the Anhui/13 H7N9 in chicken cells. In vivo co-infection experiments followed, where chickens were co-infected with pairs of Anhui/13 H7N9 and one of each of the three 2:6 H7N9 reassortants. During ensuing transmission events, the Anhui/13 H7N9 virus outcompeted 2:6 H7N9 with internal gene segments of BJ94-like or G1-like H9N2 viruses. Co-infection did lead to the emergence of novel reassortant genotypes that were transmitted to contact chickens. Some of the reassortant viruses had a greater replication in chicken and human cells compared to the progenitors. We demonstrated that the internal gene cassette determines the transmission fitness of H7N9 viruses in chickens and the reassortment events can generate novel H7N9 genotypes with increased virulence in chickens and enhanced zoonotic potential.ImportanceH9N2 avian influenza viruses (AIVs) are enzootic in poultry in different geographical regions. The internal genes of these viruses can be exchanged with other zoonotic AIVs, most notably the China-origin H7N9 that can give rise to new virus genotypes with increased veterinary, economic and public health threats to both poultry and humans. We investigated the propensity of the internal genes of H9N2 viruses (G1 or BJ94) in the generation of novel reassortant H7N9 AIVs. We observed that the internal genes of H7N9 which were derivative of BJ94-like H9N2 virus have a fitness advantage compared to those from the G1-like H9N2 viruses for efficient transmission among chickens. We also observed the generation of novel reassortant viruses during chicken transmission which infected and replicated efficiently in human cells. Therefore, such emergent reassortant genotypes may pose an elevated zoonotic threat.
Nitrite accumulation and the associated anammox bacteria niche partitioning in marine sediments
Authors: Zhao Rui , Babbin Andrew R. , Roerdink Desiree L. , Thorseth Ingunn H. , Jørgensen Steffen L. 
Published: August 2022

AbstractBy consuming ammonium and nitrite, anammox bacteria form an important functional guild in nitrogen cycling in many environments including marine sediments. Recent studies have shown that anammox bacteria can consume most of the upwardly diffusing ammonium from deep anoxic sediments; however, their impact on the other important substrate nitrite has not been well characterized. Here we show niche partitioning of two anammox families emerges in a 2.4-m long mostly anoxic sediment core retrieved from the Nordic Seas. We document high abundances (~106 cells g−1) of anammox bacteria in most investigated sediment layers, with two distinct anammox abundance maxima in two nitrite consumption zones. Between the two anammox abundance maxima, nitrite accumulates as observed in other marine sediment sites and aquatic environments, indicating anammox bacteria play a fundamental role in modulating the nitrite distribution. Anammox bacteria in the upper nitrite consumption zone are dominated by the Candidatus Bathyanammoxibiaceae family, while Ca. Scalinduaceae family dominate at the lower zone. A high-quality representative Ca. Bathyanammoxibiaceae genome is recovered, which, comparing to Ca. Scalindua sediminis, the representative of Scalinduaceae in marine sediments, has fewer high-affinity ammonium transporters and lacks the capacity to access alternative substrates or energy sources such as urea and cyanate. These features may restrict Ca. Bathyanammoxibiaceae to conditions of higher ammonium concentrations or fluxes, and therefore drive the observed niche partitioning. These findings improve our understanding about nitrogen cycling in marine sediments by revealing the association between nitrite accumulation and niche partitioning of anammox bacteria.
Dual inhibition of SHP2 and autophagy suppresses NF1-associated Malignant Peripheral Nerve Sheath Tumors
Authors: Farouk Sait Sameer , Tang Kwan-ho , Angus Steve , Brown Rebecca , Sun Daochun , Xie Xuanhua , Iltis Charlene , Lien Michelle , Socci Nicholas , Bale Tejus , Davis Christopher , Dixon Shelley A.H , Zhang Chi , Clapp D. Wade , Neel Benjamin G. , Parada Luis F. 
Published: August 2022

AbstractMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). MPNSTs develop within pre-existing benign plexiform neurofibromas (PNs). PNs are driven solely by biallelic NF1 loss eliciting RAS pathway activation and respond favorably to MEK inhibitor therapy. Our analysis of genetically engineered and orthotopic patient-derived xenograft MPNST indicates that MEK inhibition has poor anti-tumor efficacy. By contrast, upstream inhibition of RAS through the protein-tyrosine phosphatase SHP2 reduced downstream signaling and suppressed NF1 MPNST growth, although resistance eventually emerged. To investigate possible mechanisms of acquired resistance, kinomic analyses of resistant tumors was performed, and data analysis identified enrichment of activated autophagy pathway protein kinases. Combining pharmacological blockade of autophagy and SHP2 inhibition resulted in durable responses in NF1 MPNSTs in both genetic and orthotopic xenograft mouse models. Our studies can be rapidly translated into a clinical trial to evaluate SHP2 inhibition in conjunction with autophagy inhibitors as a novel treatment approach for NF1 MPNSTs.Statement of significanceCurrently, no effective therapies exist for MPNST. We demonstrate intrinsic MPNST resistance to MEKi monotherapy and identify SHP2 inhibition as an actionable vulnerability upstream of RAS. Furthermore, anti-tumor effects are extended and enhanced by dual exposure to autophagy pathway inhibition. Validation of these results as the most effective therapy to date in multiple genetically engineered models and in orthotopic patient-derived xenografts justify a clinical trial to evaluate SHP2i in conjunction with autophagy inhibitors as a novel treatment approach for NF1 MPNSTs.
The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function
Authors: Foskolou Iosifina P. , Cunha Pedro P , Minogue Eleanor , Nicolet Benoit P , Guislain Aurelie , Jorgensen Christian , Zandhuis Nordin D , Barbieri Laura , Bargiela David , Nathanael Demitris , Tyrakis Petros , Palazon Asis , Wolkers Monika C , Johnson Randall S 
Published: August 2022

SUMMARY2-hydroxyglutarate (2HG) is a by-product of the TCA cycle, and is readily detected in the tissues of healthy individuals. 2HG is found in two enantiomeric forms: S-2HG and R-2HG. Here, we investigate the differential roles of these two enantiomers in CD8+ T cell biology, where we found they had highly divergent effects on proliferation, differentiation, and T cell function. We show here an analysis of structural determinants that likely underlie these differential effects on specific a-ketoglutarate (aKG)-dependent enzymes. Treatment of CD8+ T cells with exogenous S-2HG, but not R-2HG, increased CD8+ T cell fitness in vivo, and enhanced anti-tumour activity. These data show that S-2HG and R-2HG should be considered as two distinct and important actors in the regulation of T cell function.
BCAA catabolism drives adipogenesis via an intermediate metabolite and promotes subcutaneous adipose tissue expansion during obesity
Authors: Shao Jing , Liu Yunxia , Zhang Xuejiao , Shu Le , Yu Jiayu , Yang Sa , Gao Chen , Wang Chenma , Cao Nancy , Zhou Meiyi , Chi Rui , Chen Mengping , Liu Chunliang , Wang Ji , Zhang Weiping , Liu Ruixin , Wang Jiqiu , Wang Weiqing , Ning Guang , Yang Xia , Wang Yibin , Sun Haipeng 
Published: August 2022

ABSTRACTBranched-chain amino acids (BCAAs, including leucine, isoleucine, and valine) have emerged as major players in metabolic health and diseases, but the underlying mechanisms remain obscure. Here, we report that BCAA catabolism drives adipogenesis via an intermediate metabolite of leucine and promotes subcutaneous white adipose tissue (sWAT) expansion during obesity. Genetic analyses of humans and mice reveal that the BCAA catabolic pathway in WAT is strongly correlated with adipose physiology and obesity traits. Altering BCAA catabolism in mature adipocytes exerts minor effects on adiposity in mice. However, enhancing adipose BCAA catabolism via FABP4-Cre-mediated Bckdk deletion promotes diet-induced obesity while blocking adipose BCAA catabolism through Bckdha ablation does the opposite. Intriguingly, the catabolism of BCAAs elicits fat depot-specific responses and promotes sWAT extension and adipogenesis in a cell-autonomous manner. Mechanistically, BCAA catabolism drives adipocyte differentiation via an intermediate metabolite of leucine, which activates mTORC1 and polyamine synthesis from methionine to promote the expression of adipogenic master regulators. Together, these results demonstrate that BCAA catabolism promotes adipogenesis and sWAT expansion during obesity. The crosstalk between leucine and methionine metabolism driven by the catabolic intermediate highlights an unexpected regulatory role of amino acids in metabolic health and diseases.
Efficient meta-analysis of multivariate genome-wide association studies with Meta-MOSTest
Authors: Lin Aihua , Shadrin Alexey , van der Meer Dennis , Hindley Guy , Cheng Weiqiu , Sønderby Ida Elken , Bahrami Shahram , O’Connell Kevin S , Rahman Zillur , Parker Nadine , Smeland Olav B , Fan Chun C. , Holland Dominic , Dale Anders M , Andreassen Ole A , Frei Oleksandr 
Published: August 2022

AbstractMotivationGenome-wide association studies (GWAS) have been successful in identifying genetic variants associated with a particular phenotype. However, many complex phenotypes are influenced by multiple genetic variants with small effects. Detecting the genetic pleiotropy can provide insights into biological mechanisms influencing complex human phenotypes. The recently developed Multivariate Omnibus Statistical Test (MOSTest) has proven to be efficient and powerful, suited for complex large-scale data. The method substantially increased discovery of genetic variants associated with brain MRI phenotypes in the UK Biobank compared to conventionally use multivariate approach. Here we extend the MOSTest to meta-analysis (Meta-MOSTest), facilitating data analysis of multiple phenotypes across multiple cohorts. We evaluated our updated approach in the UK Biobank using brain MRI phenotypes, by comparing the discovery yield of the single-cohort MOSTest versus Meta-MOSTest through simulating sub-cohorts of different sample sizes from 265 to 26501 subjects.ResultsOur method works efficiently on large-scale cohorts with a large number of MRI phenotypes. We found that lower per-cohort sample sizes resulted in a reduced discovery yield indicating a loss of statistical power. However, with a minimum sample size of 250 subjects across cohorts, Meta-MOSTest was equivalent to MOSTest on discovery yield while maintaining a well-calibrated type I error and equivalent statistical power. We conclude that Meta-MOSTest is a useful tool for multivariate analysis across separate brain imaging genetics cohorts.Availability and implementationAll codes are freely available on GitHub: MOSTest and Meta-MOSTest.
Thermal modulation of skin friction at the fingertip
Authors: Filingeri Davide , Worsley Peter , Bader Dan , Martinez Daniel M. , Rykaczewski Konrad 
Published: August 2022

AbstractPreliminary human studies show that reduced skin temperature minimises the risk of mechanically-induced skin damage. However, the mechanisms by which cooling enhances skin tolerance to pressure and shear remain poorly understood. We hypothesized that skin cooling below thermo-neutral conditions will decrease friction at the skin-material interface. To test our hypothesis, we measured the friction coefficient of a thermally pre-conditioned index finger sliding at a normal load (5N) across a plate maintained at three different temperatures (38, 24, and 16□). To quantify the temperature distribution of the skin tissue, we used 3D surface scanning and Optical Coherence Tomography to develop an anatomically-representative thermal model of the finger. Our data indicated that the sliding finger with thermally affected tissues (up to 8mm depth) experienced significantly (p<0.01) lower frictional forces at 16°C-plate temperature than at the 24°C [-23% (±19% SD)] and 38°C plate interactions [-35% (±11% SD)], respectively. This phenomenon occurred without changes in skin hydration during sliding. Accordingly, our experiments demonstrate thermal modulation of skin friction in the absence of skin-moisture effects. Our complementary experimental and theoretical results provide new insight into thermal modulation of skin friction that can be employed for developing thermal technologies to maintain skin integrity under mechanical loading.
Socio-cultural capital in the Arab workplace: wasta as a moderator of ethical idealism and work engagement
Authors: Stefanidis Abraham , Banai Moshe , Dagher Grace K. 
Published: August 2022

PurposeThis study refines theory of social capital by nesting it within a cultural context. More specifically, it aims at describing, explaining, and predicting the role of wasta, a social capital concept, as a moderator in the relationship between employees' ethical idealism and work engagement in Lebanon.Design/methodology/approachBased on a survey questionnaire translated from English into Arabic, 317 responses were collected from employees in Lebanon. Confirmatory factor analysis and hierarchical regression analysis were employed to test the hypothesized relationships among the examined variables.FindingsEthical idealism was found to be positively related to work engagement, and wasta was found to moderate the relationship between ethical idealism and work engagement. Work engagement levels of employees who displayed high levels of ethical idealism were less influenced by the negative effect of wasta than work engagement levels of employees who displayed low levels of ethical idealism.Practical implicationsHuman resource managers, international negotiators, and global executives in Lebanon may use the findings of this study to update corporate human resources systems, such as employee recruitment and selection, handbooks, orientation, training programs, and performance appraisal, to better address employee attitudes toward the practice of wasta.Originality/valueThe study adds ethical idealism as an antecedent of work engagement, demonstrating the significant impact that wasta, with its positive and negative characteristics, has on the engagement of employees from the Arab world.
Interrogating “entrepreneurship for development”: a counter-narrative based on local stories of women in rural Ethiopia
Authors: Cummings Sarah J.R. , Lopez Diana E. 
Published: August 2022

PurposeTo interrogate the grand narrative of “entrepreneurship for development” that dominates international development circles, by applying a feminist critical discourse analysis that prioritizes women's situated experiences as local stories.Design/methodology/approachTwo existing frameworks for analysing women's entrepreneurship, namely the 5M (Brush et al., 2009) and the 8M (Abuhussein and Koburtay, 2021) frameworks, are used to examine the local stories of women in rural Ethiopia to provide a counter-narrative to the grand narrative of “entrepreneurship for development”. The local stories are derived from 16 focus group discussions and 32 interviews.FindingsThe findings provide a counter-narrative to the grand narrative of “entrepreneurship for development”, evident in Ethiopia and in international development generally, while demonstrating larger structural issues at play. They challenge entrepreneurship's solely positive effects. While women recognize the benefits of having a business, particularly in terms of financial gains, empowerment and social recognition, they also highlight negative consequences, including uncertainty, concerns for their own personal safety, criticism, stress, limited social life and fear of indebtedness and poverty.Practical implicationsPolicymakers, scholars and development professionals are urged to reflect on the limitations of “entrepreneurship for development” and to consider the negative effects that promoting an acritical grand narrative of entrepreneurship could have on women's lives.Originality/valueThe article advances an innovative partnership between feminist analysis and established women's entrepreneurship frameworks to contest dominant assumptions in the fields of entrepreneurship and international development studies. It adds to the limited empirical evidence on women's entrepreneurial activity in Ethiopia, tests the adequacy of the 5M and 8M frameworks in the rural low-income context of Ethiopia, and proposes a 7+M framework as an alternative to study rural women's entrepreneurship in low and middle income countries.
Leadership integrity and employees’ success: role of ethical leadership, psychological capital, and psychological empowerment
Authors: Yazdanshenas Mehdi , Mirzaei Mehdi 
Published: August 2022

Purpose
This study aims to investigate the effect of leadership integrity on employees’ success. In this regard, the mediating role of ethical leadership and the moderating role of psychological capital and psychological empowerment were considered as well.

Design/methodology/approach
This study is an applied research and a descriptive-correlation survey that used quantitative data. Data were collected from 302 employees of a large factory in Iran who was selected randomly. The research questionnaire consisted of 54 statements and was distributed among the sample. Data was analyzed through confirmatory factor analysis and structural equation modeling.

Findings
The findings of this study show that leader integrity and ethical leadership have a positive effect on employees’ success and psychological capital and psychological empowerment moderate these effects. Moreover, leader integrity has an indirect effect on employees` success through employees’ perception of ethical leadership.

Originality/value
This study mainly contributes by explaining two sets of variables related to leaders’ behavior and employees’ cognitive competence which are complementary in improving employees’ potential success. The results highlight that leaders’ behavioral integrity can amplify ethical leadership which can ultimately leads to employees’ success if they have a high psychological empowerment and psychological capital.