bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and mechanism of the type I-G CRISPR effector
Authors: Shangguan Qilin , Graham Shirley , Sundaramoorthy Ramasubramanian , White Malcolm F 
Published: August 2022

ABSTRACTType I CRISPR systems are the most common CRISPR type found in bacteria. They use a multisubunit effector, guided by crRNA, to detect and bind dsDNA targets, forming an R-loop and recruiting the Cas3 enzyme to facilitate target DNA destruction, thus providing immunity against mobile genetic elements. Subtypes have been classified into families A-G, with type I-G being the least well understood. Here, we report the composition, structure and function of the type I-G Cascade CRISPR effector from Thioalkalivibrio sulfidiphilus, revealing key new molecular details. The unique Csb2 subunit processes pre-crRNA, remaining bound to the 3’ end of the mature crRNA, and seven Cas7 subunits form the backbone of the effector. Cas3 associates stably with the effector complex via the Cas8g subunit and is important for target DNA recognition. Structural analysis by cryo-Electron Microscopy reveals a strikingly curved backbone conformation with Cas8g spanning the belly of the structure. Type I-G Cascade is one of the most streamlined Class 1 CRISPR effectors. These biochemical and structural insights shed new light on the diversity of type I systems and open the way to applications in genome engineering.
An efficient and robust tool for colocalisation: Pair-wise Conditional and Colocalisation (PWCoCo)
Authors: Robinson Jamie W , Hemani Gibran , Babaei Mahsa Sheikhali , Huang Yunfeng , Baird Denis A , Tsai Ellen A , Chen Chia-Yen , Gaunt Tom R , Zheng Jie 
Published: August 2022

AbstractGenetic colocalisation is an important tool to test for shared genetic aetiology and is commonly used to strengthen causal inference in genetic studies of molecular traits and drug targets. However, the single causal variant assumption of the original colocalization method is a considerable limitation in genomic regions with multiple causal effects.We integrated conditional analyses (GCTA-COJO) and colocalisation analyses (coloc), into a novel analysis tool called Pair-Wise Conditional Colocalization (PWCoCo). PWCoCo performs conditional analyses to identify independent signals for the two tested traits in a genomic region and then conducts colocalisation of each pair of conditionally independent signals for the two traits using summary-level data. This allows for the stringent single-variant assumption to hold for each pair of colocalisation analysis.We found that the computational efficiency of PWCoCo is on average better than colocalisation with Sum of Single Effects Regression using Summary Stats (SuSiE-RSS), with greater gains in efficiency for high-throughput analysis. In a case study using GWAS data for multiple sclerosis and brain cortex-derived eQTLs (MetaBrain), we recapitulated all previously identified genes, which showcased the robustness of the method. We further found colocalisation evidence for secondary signals in nine additional loci, which was not identifiable in conventional GWAS and/or colocalisation.PWCoCo offers key improvements over existing methods, including: (1) robust colocalisation when the single variant assumption is violated; (2) independent colocalisation of secondary signals, which enables identification of novel disease-causing variants; (3) an easy-to-use and computationally efficient tool to test for colocalisation of high-dimensional omics data.
Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding scavenger receptor B1
Authors: Fung Karen Y. Y. , Ho Tse Wing Winnie , Xu Zizhen , Neculai Dante , Beauchemin Catherine A. A. , Lee Warren L. , Fairn Gregory D. 
Published: August 2022

AbstractAtherosclerosis results from the deposition and oxidation of low-density lipoprotein (LDL) and immune cell infiltration in the sub-arterial space leading to arterial occlusion. Numerous studies have shown that transcytosis transports circulating LDL across endothelial cells lining the blood vessels. LDL transcytosis is initiated by binding to either Scavenger Receptor B1 (SR-B1) or Activin A receptor-like kinase 1 (ALK1) on the apical side of endothelial cells leading to its transit and release on the basolateral side. Individuals with elevated levels of circulating high-density lipoprotein (HDL) are partly protected from atherosclerosis due to its ability to remove excess cholesterol and act as an antioxidant. Apolipoprotein A1 (APOA1), an HDL constituent, can bind to SR-B1, raising the possibility that APOA1/HDL may also compete with LDL for SR-B1 binding and thereby limit LDL deposition in the sub-arterial space. To examine this possibility, we usedin vitroapproaches to quantify the internalization and transcytosis of fluorescent LDL in coronary endothelial cells. Using microscale thermophoresis and affinity capture, we find that SR-B1 and APOA1 directly interact, and that binding is enhanced when using the cardioprotective variant of APOA1 termed Milano (APOA1-Milano). In a murine model, transiently increasing the levels of HDL reduced the acute deposition of fluorescently labeled LDL in the atheroprone inner curvature of the aorta. Reduced LDL deposition was also observed when increasing circulating wild-type APOA1 or the APOA1-Milano variant, with a more robust inhibition from the APOA1-Milano. The results suggest that HDL may limit SR-B1-mediated LDL transcytosis and deposition, adding to the mechanisms by which it can act as an atheroprotective particle.
Monkeypox virus contamination in an office-based workplace environment, England 2022
Authors: Atkinson Barry , Gould Susan , Spencer Antony , Onianwa Okechukwu , Furneaux Jenna , Grieves James , Summers Sian , Crocker-Buqué Tim , Fletcher Tom , Bennett Allan M , Dunning Jake 
Published: August 2022

AbstractIn May 2022, an office worker attended their place of work while experiencing prodromal symptoms of monkeypox infection. Environmental sampling performed four days later identified only low levels of monkeypox virus DNA contamination of the worker’s desk, and no contamination elsewhere within the office. Replication-competent virus was not identified.
IFT-A Structure Reveals Carriages for Membrane Protein Transport into Cilia
Authors: Hesketh Sophie J. , Mukhopadhyay Aakash G. , Nakamura Dai , Toropova Katerina , Roberts Anthony J. 
Published: August 2022

ABSTRACTIntraflagellar transport (IFT) trains are molecular machines that traffic proteins between cilia and the cell body. With a molecular weight over 80 MDa, each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes; interacts with IFT-B; and uses an array of β-propeller and TPR domains to create “carriages” of the IFT train that engage TULP adaptor proteins. We show that IFT-A·TULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK – the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A’s distinct functions, provide a blueprint for the IFT-A train, and shed light on how IFT evolved from a proto-coatomer ancestor.
Spike-specific CXCR3+ TFH cells play a dominant functional role in supporting antibody responses in SARS-CoV-2 infection and vaccination
Authors: Zhang Jian , He Rongzhang , Liu Bo , Zheng Xingyu , Wu Qian , Wen Bo , Wang Qijie , Liu Ziyan , Chang Fangfang , Hu Yabin , Xie Ting , Liu Yongchen , Chen Jun , Yang Jing , Teng Shishan , Bai Tingting , Peng Yanxi , Liu Ze , Peng Yuan , Huang Weijin , Terzieva Velislava , Wang Youchun , Liu Wenpei , Li Yi-Ping , Qu Xiaowang 
Published: August 2022

SummaryCD4+ T follicular helper (TFH) cells are required for high-quality antibody generation and maintenance. However, the longevity and functional role of these cells are poorly defined in COVID-19 convalescents and vaccine recipients. Here, we longitudinally investigated the dynamics and functional roles of spike-specific circulating TFH cells and their subsets in convalescents at the 2nd, 5th, 8th, 12th and 24th months after COVID-19 symptom onset and in vaccinees after two and three doses of inactivated vaccine. SARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, of which spike-specific CXCR3+ TFH cells but not spike-specific CXCR3− TFH cells and neutralizing antibodies were persistent for at least two years in more than 80% of convalescents who experienced symptomatic COVID-19, which was well coordinated between spike-specific TFH cell and antibody responses at the 5th month after infection. Inactivated vaccine immunization also induced spike-specific TFH cell and antibody responses; however, these responses rapidly declined after six months with a two-dose standard administration, and a third dose significantly promoted antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells exhibited better responsiveness than spike-specific CXCR3− TFH cells upon spike protein stimulation in vitro and showed superior capacity in supporting spike-specific antibody secreting cell (ASC) differentiation and antibody production than spike-specific CXCR3− TFH cells cocultured with autologous memory B cells. In conclusion, spike-specific CXCR3+ TFH cells played a dominant functional role in antibody elicitation and maintenance in SARS-CoV-2 infection and vaccination, suggesting that induction of CXCR3-biased spike-specific TFH cell differentiation will benefit SARS-CoV-2 vaccine development aiming to induce long-term protective immune memory.HighlightsSARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, which persisted for at least two years in the majority of symptomatic COVID-19 convalescent patients.Inactivated vaccine immunization also elicited spike-specific TFH cell and antibody responses, which rapidly declined over time, and a third dose significantly promoted antibody maturation and potency.Spike-specific CXCR3+ TFH cells exhibited more durable responses than spike-specific CXCR3− TFH cells, correlated with antibody responses and showed superior capacity in supporting ASC differentiation and antibody production than spike-specific CXCR3− TFH cells.
The quality of management schools, the ethical behavior of firms and sustainability level: a cross-country investigation
Authors: Guidara Achraf 
Published: August 2022

PurposeThis paper examines the association between the quality of management schools and sustainability and investigates whether ethical behavior of firms moderates relationship between the quality of management schools and sustainability.Design/methodology/approachThe sample consists of 500 country-year observations over the period of 2014-2017. Sustainability is collected from the Global Sustainable Competiveness Index reports for 2014, 2015, 2016 and 2017, while the quality of management schools and ethical behavior of firms are collected from the Global Competiveness Report for the same years.FindingsThe findings of this study suggest that the quality of management schools is positively associated with sustainability. When testing for the moderating effect of ethical behavior of firms on the association between quality of management schools and sustainability, results show that the positive association becomes positive and more significant for countries where firms operate with high ethical behaviors, while the association becomes insignificant for settings where firms operate with low ethical behaviors. Findings also show that the quality of management schools and ethical behavior of firms play a complimentary role in improving sustainability.Social implicationsThe findings emphasize the role played by business schools and business ethics in improving sustainability. These results may have policy implications for governments aiming to improve sustainability by emphasizing on education for sustainable development in management schools’ 2019 programs enforcing standards dealing with business ethics and controlling firms’ 2019 compliance with them.Originality/valueThe findings of this study highlight the importance of education, as proxied by the quality of management schools, in the development of sustainable societies and economic systems. To the best of the author's knowledge, this is the first study that tries to empirically link business schools programs to sustainability efforts and how business ethics may affect this association.
Challenging cisnormativity, gender binarism and sex binarism in management research: foregrounding the workplace experiences of trans* and intersex people
Authors: Köllen Thomas , Rumens Nick 
Published: August 2022

Purpose
This paper aims to challenge the cisnormative and binary assumptions that underpin the management and gender scholarship. Introducing and contextualising the contributions that comprise this special issue, this paper critically reflects on some of the principal developments in management research on trans* and intersex people in the workplace and anticipates what future scholarship in this area might entail.

Design/methodology/approach
A critical approach is adopted to interrogate the prevailing cisnormative and binary approach adopted by management and gender scholars.

Findings
The key finding is the persistence of cisnormativity and normative gender and sex binarism in academic knowledge production and in society more widely, which appear to have hindered how management and gender scholars have routinely failed to conceptualise and foreground the array of diverse genders and sexes.

Originality/value
This paper foregrounds the workplace experiences of trans* and intersex people, which have been neglected by management researchers. By positioning intersexuality as an important topic of management research, this paper breaks the silence that has enwrapped intersex issues in gender and management scholarship. There are still unanswered questions and issues that demand future research from academics who are interested in addressing cisnormativity in the workplace and problematising the sex and gender binaries that sustain it.
Capacity issues in primary health care implementation: examples from Ghana
Authors: Appiah-Agyekum Nana Nimo , Kayi Esinam Afi , Appiah-Agyekum Josephine , Tetteh Nyanyofio Joseph Gerald , Otoo Desmond Dzidzornu 
Published: August 2022

PurposeResources as well as the capacity to employ them judiciously may well be the key to the attainment of the SDGs and other related health goals through primary health care (PHC). Within this PHC framework, however, the source of resources for PHC as well as the systems for managing these associated resources remain unclear, complex and lack substantive integration systems of implementing ministries, departments and agencies (both local and international) in Ghana. These issues are addressed by this study.Design/methodology/approachThe framework approach to thematic analysis was used to analyse qualitative data collected from key PHC managers in Ghana selected purposively from the national, regional and district levels. Data were collected through in-depth interviews specially designed in line with the study objectives. The study was also governed by the Noguchi Memorial Institute for Medical Research which provided ethical clearance for the study.FindingsAs per Alma Ata's recommendation, PHC in its purest form is a resource dense activity with far-reaching implications on individuals and communities. Without adequate resources, PHC implementation remained merely on paper. Findings show that the key capacities required for PHC implementation were finance, human resource, technology and logistics. While significant cases of shortages and inadequacies were evident, management and maintenance of these capacities appeared to be another significant determinant of PHC implementation. Additionally, the poor allocation, distribution and sustainability of these capacities had a negative effect on PHC outcomes with more resources being concentrated in capital towns than in rural areas.Research limitations/implicationsThis study has significant implications on the way PHC is seen, implemented and assessed not in Ghana but in other developing countries. In addition to examining the nature and extent of capacities required for PHC implementation, it gives significant pathways on how limited resources, when properly managed, may catalyse the attainment of the PHC goals. Subsequently, PHC implementation will profit from stakeholder attention and further research into practical ways of ensuring efficiency in the allocation, distribution and management of resources especially considering the limited resources available and the budding constraints associated with the dependency on external stakeholders for PHC implementation.Originality/valueThis study is part of a series on PHC implementation in Ghana. Quite apart from putting core implementation issues into perspective, it presents first-hand information on Ghana's PHC implementation journey and is thus relevant for researchers, students, practitioners and the wider public.
Value co-creation in the multinational technology standard alliance: a case study from emerging economies
Authors: Zhou Qing , Zhang Yue , Yang Wei , Ren Liqin , Chen Ping 
Published: August 2022

PurposeThis paper aims to explore and analyze how a focal firm, coming from emerging economies, of the multinational technology standard alliance ecosystem engages different actors of the alliance in value co-creation practice, contributing to product collaborative innovation and reciprocal standards cooperation.Design/methodology/approachBased on in-depth interviews, primary company, and secondary documents, this paper conducts an exploratory single case study of TechAlpha to investigate the practice of value co-creation in the multinational technology standard alliance (MTSA).FindingsBased on the extended resource-based view (ERBV), this paper finds that in the MTSA ecosystem, actor engagement sets the anchor for the focal firm in the MTSA to dominate the resource interaction, achieving a greater interaction through goal co-discussion, standard co-construction and achievement co-sharing. Resource interaction is composed of standard resource identification, standard resource sharing, and standard resource alignment, putting a high value on the practice of value co-creation. Value co-creation dominated by the focal firm of the MTSA is embodied in the synergy of actor engagement and resource interaction.Originality/valueThis paper contributes to the relevant literature by illustrating how the focal firm coming from emerging economies of the MTSA enables value co-creation through adjusting the situation of actor engagement and exerting its standards resource interaction. This paper also advances the process of acquisition, integration, and reconstruction of heterogeneous resources throughout the MTSA by offering a new supplementary perspective and new evidence from a Chinese firm.
Consumer data vulnerability, peer privacy concerns and continued usage intention of sharing accommodation platforms: the moderating roles of perceived benefits
Authors: Liu Tingting , Li Wenqian , Jia Xingping 
Published: August 2022

PurposeThis study aims to explore the relationships between consumer data vulnerability, peer privacy concerns and consumers' continued usage intention of sharing accommodation platforms, as well as the moderating effects of the various benefits perceived by consumers.Design/methodology/approachData were collected from 327 consumers of sharing accommodation platforms in China. Partial least squares (PLS)-structural equation modeling (SEM) was conducted to test the research hypotheses.FindingsThe results suggest that both consumer data vulnerability and peer privacy concerns have negative effects on consumer's continued usage intention of sharing accommodation platforms, which can be further mitigated by consumer perceived economic, social and emotional benefits. This study also finds that consumer data vulnerability has a positive effect on consumer's peer privacy concerns.Practical implicationsThis study gives that managers of sharing accommodation platforms a better understanding of how consumers respond to their data vulnerability on sharing accommodation platforms. In addition, this study also highlights the measures that platforms may employ to mitigate the negative influence of consumer data vulnerability and consumers' peer privacy concerns, as well as the measures to reduce consumers' peer privacy concerns.Originality/valueWhile previous studies mainly examined the driving forces of consumers' engagement in sharing accommodation, this study focuses on the impediment. With communication privacy management theory to explore the relationships between consumer data vulnerability, peer privacy concerns and continued usage intention of sharing accommodation platforms, as well as the moderating effects of consumers' perceived benefits, this study facilitates a more comprehensive understanding of consumers' engagement in sharing accommodation.
Policy uncertainty, social responsibility and corporate M&A
Authors: Li Cong , Lan Gongxu , Zhang Guitao , Cheng Peiyue , Shi Yangyan , Gao Yangfei 
Published: August 2022

Purpose
This paper aims to focus on corporate social responsibility in relation to economic policy uncertainty in mergers and acquisitions (M&A). The following questions are addressed: How does policy uncertainty impact corporate M&A? Does social responsibility play a mediating role in this process? How does policy uncertainty affect corporate M&A through social responsibility?

Design/methodology/approach
This paper selects the major M&A events in China as the research object, and uses the Probit model to analyze the impact of policy uncertainty on M&A behavior and the business performance after the event, and further analyzes the internal mechanisms that cause these phenomena.

Findings
This paper shows that the higher the policy uncertainty, the lower the probability of a successful M&A, and the worse the business performance of the business after the event.

Originality/value
This paper provides useful reference for the study of M&A and social responsibility in different policy environments. At the same time, it provides direct empirical evidence to enhance the success rate of M&A.
Favor reciprocity, innovation and inefficiency: the double-edged sword of business-to-businesswastarelations
Authors: AlHussainan Omar , Guo Ying , Rammal Hussain Gulzar , Tang Ryan W. , Golgeci Ismail 
Published: August 2022

PurposeThe purpose of this study is to empirically investigate the dark side of business-to-business (B2B) relationships in traditional business practices worldwide that rely on strong networks.Design/methodology/approachThis study applies a questionnaire survey to collect data from buyers in 224 Kuwaiti firms and uses the partial least squares structural equation model for data analysis.FindingsDrawing on the social exchange theory, we test the relationships between B2B wasta, relationship satisfaction, innovation and efficiency. The findings show that despite the belief that wasta brings long-term benefits when applied in B2B relationships, it negatively impacts the firm’s efficiency.Originality/valueThis study contributes to the existing literature on B2B relationships by identifying important issues related to the multifaceted nature of B2B wasta relationships. The study confirms the importance of relational and innovation benefits over economic consequences based on elements of social exchange theory, which extends our current understanding of the application of SET in B2B wasta relationships.