bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern
Authors: Li Wenwei , Chen Yaozong , Prévost Jérémie , Ullah Irfan , Lu Maolin , Gong Shang Yu , Tauzin Alexandra , Gasser Romain , Vézina Dani , Anand Sai Priya , Goyette Guillaume , Chaterjee Debashree , Ding Shilei , Tolbert William D. , Grunst Michael W. , Bo Yuxia , Zhang Shijian , Richard Jonathan , Zhou Fei , Huang Rick K. , Esser Lothar , Zeher Allison , Côté Marceline , Kumar Priti , Sodroski Joseph , Xia Di , Uchil Pradeep D. , Pazgier Marzena , Finzi Andrés , Mothes Walther 
Published: August 2021

SummaryEmerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remained effective against emerging variants of concern in vitro and in vivo. CV3-1 bound to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the “RBD-up” position and triggered potent shedding of the S1 subunit. In contrast, CV3-25 inhibited membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.
The ER transmembrane complex (EMC) can functionally replace the Oxa1 insertase in mitochondria
Authors: Güngör Büsra , Flohr Tamara , Garg Sriram G. , Herrmann Johannes M. 
Published: August 2021

AbstractTwo multisubunit protein complexes for membrane protein insertion were recently identified in the endoplasmic reticulum (ER): The guided entry of tail anchor proteins (GET) complex and ER membrane complex (EMC). The structures of both of their hydrophobic core subunits, that are required for the insertion reaction, revealed an overall similarity to the YidC/Oxa1/Alb3 family members found in bacteria, mitochondria and chloroplasts. This suggests that these membrane insertion machineries all share a common ancestry. To test whether these ER proteins can functionally replace Oxa1 in yeast mitochondria, we generated strains that express mitochondria-targeted Get2-Get1 and Emc6-Emc3 fusion proteins in Oxa1 deletion mutants. Interestingly, the Emc6-Emc3 fusion was able to complement an Δoxa1 mutant and restored its respiratory competence. The Emc6-Emc3 fusion promoted the insertion of the mitochondrially encoded protein Cox2 as well as of nuclear encoded inner membrane proteins though was not able to facilitate the assembly of the Atp9 ring. Our observations indicate that protein insertion into the ER is functionally conserved to the insertion mechanism in bacteria and mitochondria and adheres to similar topological principles.
Transcriptome Profiles of Anopheles gambiae Harboring Natural Low-Level Plasmodium Infection Reveal Adaptive Advantages for the Mosquito
Authors: Carr Ann , Rinker David C. , Dong Yuemei , Dimopoulos George , Zwiebel Laurence J. 
Published: August 2021

AbstractAnopheline mosquitoes are the sole vectors for the Plasmodium pathogens responsible for malaria, which is among the oldest and most devastating of human diseases. The continuing global impact of malaria reflects the evolutionary success of a complex vector-pathogen relationship that accordingly has been the long-term focus of both debate and study. An open question in the biology of malaria transmission is the impact of naturally occurring low-level Plasmodium infections of the vector on the mosquito’s health and longevity as well as critical behaviors such as host- preference/seeking. To begin to answer this, we have completed a comparative RNAseq-based transcriptome profile study examining the effect of biologically salient, salivary gland transmission- stage Plasmodium infection on the molecular physiology of Anopheles gambiae s.s. head, sensory appendage, and salivary glands. When compared with their uninfected counterparts, Plasmodium infected mosquitoes exhibit increased transcript abundance of genes associated with olfactory acuity as well as a range of synergistic processes that align with increased fitness based on both anti-aging and reproductive advantages. Taken together, these data argue against the long-held paradigm that malaria infection is pathogenic for anophelines and, instead, suggests there are biological and evolutionary advantages for the mosquito that drive the preservation of its high vectorial capacity.
Recombinant Lloviu virus as a model to study inaccessible zoonotic viruses
Authors: Hume Adam J , Heiden Baylee , Olejnik Judith , Suder Ellen L , Ross Stephen , Scoon Whitney A , Bullitt Esther , Ericsson Maria , White Mitchell R , Turcinovic Jacquelyn , Thao Tran TN , Hekman Ryan M , Kaserman Joseph E , Huang Jessie , Alysandratos Konstantinos-Dionysios , Toth Gabor E , Jakab Ferenc , Kotton Darrell N , Wilson Andrew A , Emili Andrew , Thiel Volker , Connor John H , Kemenesi Gabor , Cifuentes Daniel , Mühlberger Elke 
Published: August 2021

AbstractNext generation sequencing has revealed the presence of many RNA viruses in animal reservoir hosts, including many closely related to known human pathogens. Despite their zoonotic potential, many of these viruses remain understudied due to not yet being cultured. While reverse genetic systems can facilitate virus rescue, this is often hindered by missing viral genome ends. A prime example is Lloviu virus (LLOV), an uncultured filovirus that is closely related to the highly pathogenic Ebola virus. Using minigenome systems, we complemented the missing LLOV genomic ends and identified cis-acting elements required for LLOV replication that were lacking in the published sequence. We leveraged these data to generate recombinant full-length LLOV clones and rescue infectious virus. Recombinant LLOV (rLLOV) displays typical filovirus features, as shown by electron microscopy. Known target cells of Ebola virus, including macrophages and hepatocytes, are permissive to rLLOV infection, suggesting that humans could be potential hosts. However, inflammatory responses in human macrophages, a hallmark of Ebola virus disease, are not induced by rLLOV. We also used rLLOV to test antivirals targeting multiple facets of the replication cycle. Rescue of uncultured viruses of pathogenic concern represents a valuable tool in our arsenal against pandemic preparedness.
A distinct inner nuclear membrane proteome in Saccharomyces cerevisiae gametes
Authors: Shelton Shary N. , Smith Sarah E. , Unruh Jay R. , Jaspersen Sue L. 
Published: August 2021

AbstractThe inner nuclear membrane (INM) proteome regulates gene expression, chromatin organization, and nuclear transport, however, it is poorly understood how changes in INM protein composition contribute to developmentally regulated processes, such as gametogenesis. Using a split-GFP complementation system, we compared the distribution of all C-terminally tagged transmembrane proteins in Saccharomyces cerevisiae in gametes to that of mitotic cells. Gametes contain a distinct INM proteome needed to complete gamete formation, including expression of genes linked to cell wall biosynthesis, lipid biosynthetic and metabolic pathways, protein degradation and unknown functions. Based on the inheritance pattern, INM components are made de novo in the gametes. Whereas mitotic cells show a strong preference for proteins with small extraluminal domains, gametes do not exhibit this size preference likely due to the changes in the nuclear permeability barrier during gametogenesis.
Heme stimulates platelet mitochondrial oxidant production via the activation of toll-like receptor 4 signaling to mediate targeted granule secretion
Authors: Annarapu Gowtham K. , Nolfi-Donegan Deirdre , Reynolds Michael , Wang Yinna , Kohut Lauren , Zuckerbraun Brian , Shiva Sruti 
Published: August 2021

AbstractHemolysis is a pathological component of many diseases and is associated with thrombosis and vascular dysfunction. Hemolytic products, including cell-free hemoglobin and free heme directly activate platelets. However, the effect of hemolysis on platelet degranulation, a central process in not only thrombosis, but also inflammatory and mitogenic signaling, remains less clear. Our group showed that hemoglobin-induced platelet activation involved the production of mitochondrial reactive oxygen species (mtROS). However, the molecular mechanism by which extracellular hemolysis induces platelet mtROS production, and whether the mtROS regulate platelet degranulation remains unknown. Here, we demonstrate using isolated human platelets that cell free heme is a more potent agonist for platelet activation than hemoglobin, and stimulates the release of a specific set of molecules from the α-granule of platelets, including the glycoprotein thrombospondin-1 (TSP-1). We uncover the mechanism of heme-mediated platelet mtROS production which is dependent on the activation of platelet TLR4 signaling and leads to the downstream phosphorylation of complex-V by the serine kinase Akt. Notably, inhibition of platelet TLR4 or Akt, or scavenging mtROS prevents heme-induced granule release in vitro. Further, heme-dependent granule release is significantly attenuated in vivo in mice lacking TLR4 or those treated with the mtROS scavenger MitoTEMPO. These data elucidate a novel mechanism of TLR4-mediated mitochondrial regulation, establish the mechanistic link between hemolysis and platelet degranulation, and begin to define the heme and mtROS-dependent platelet secretome. These data have implications for hemolysis-induced thrombo-inflammatory signaling and for the consideration of platelet mitochondria as a therapeutic target in hemolytic disorders.Key pointsHeme induces platelet mtROS production by inhibiting complex-V activity via TLR4 signaling.Heme stimulated platelet granule secretion is regulated by mtROS.
Genome-wide RNA structure changes during human neurogenesis drive gene regulatory networks
Authors: Wang Jiaxu , Zhang Tong , Yu Zhang , Tan Wen Ting , Wen Ming , Shen Yang , Lambert Finnlay R.P. , Huber Roland G. , Wan Yue 
Published: August 2021

AbstractThe distribution, dynamics and function of RNA structures in human development is under- explored. Here, we systematically assayed RNA structural dynamics and its relationship with gene expression, translation and decay during human neurogenesis. We observed that the human ESC transcriptome is globally more structurally accessible than that of differentiated cells; and undergo extensive RNA structure changes, particularly in the 3’UTR. Additionally, RNA structure changes during differentiation is associated with translation and decay. We also identified stage-specific regulation as RBP and miRNA binding, as well as splicing is associated with structure changes during early and late differentiation, respectively. Further, RBPs serve as a major factor in structure remodelling and co-regulates additional RBPs and miRNAs through structure. We demonstrated an example of this by showing that PUM2-induced structure changes on LIN28A enable miR-30 binding. This study deepens our understanding of the wide-spread and complex role of RNA-based gene regulation during human development.
Entrepreneurship and sustainable innovation capabilities in platform enterprises: the mediating role of knowledge integration
Authors: Sun Xinbo , Zhao Donghui , Zhang Dapeng , Tian Feng 
Published: August 2021

PurposeThe concept of entrepreneurship in platform enterprises has evolved and developed. The purpose of this paper is to explore how entrepreneurship in platform enterprises can be transformed into the sustainable innovation capability of enterprises based on knowledge integration.Design/methodology/approachThis study adopts a questionnaire survey. The research samples are mainly from well-known domestic platform enterprises, EMBA students and professional online websites, 389 valid questionnaires were collected.FindingsThe results show that entrepreneurship has a positive impact on the sustainable innovation capability of platform enterprises, knowledge integration plays a partial mediating role between entrepreneurship and sustainable innovation capability of platform enterprises. Shared leadership plays a moderating role between entrepreneurship and knowledge integration and knowledge-sharing atmosphere plays a moderating role between knowledge integration and sustainable innovation capability of platform enterprises.Originality/valueThis paper emphasizes the key role of entrepreneurship in platform enterprises on the sustainable innovation capability and discusses the realization path of the sustainable innovation capability of platform enterprises from the perspective of knowledge integration, which is of great significance for developing the research system of entrepreneurship and promoting the construction of sustainable innovation capability of platform enterprises.
The nexus between firm size, growth and profitability: new panel data evidence from Asia–Pacific markets
Authors: Yadav Inder Sekhar , Pahi Debasis , Gangakhedkar Rajesh 
Published: August 2021

PurposeThe purpose of this paper is to examine the correlation between firm size, growth and profitability along with other firm-specific variables (like leverage, competition and asset tangibility), macroeconomic variable (like GDP growth-business cycle) and stock market development variable (like MCR).Design/methodology/approachUsing the COMPUSTAT Global database this work uses panel dynamic fixed effects model for nearly 12,001 unique non-financial listed and active firms from 1995 to 2016 for 12 industrial and emerging Asia–Pacific economies. This interrelationship was also examined for small, medium and large size companies classified based on three alternate measures such as total assets, net sales and MCR of firms.FindingsThe persistence of profits coefficient was found to be positive and modest. There is evidence of a negative size-profitability and positive growth-profitability relationship suggesting that initially profitability increases with the growth of the firm but eventually, overtime, gains in profit rates reduce, as size increases indicting that large size breeds inefficiency. The relationship between firm's leverage ratio and its asset tangibility is found to be negative with profitability. The business cycle and stock market development variables suggest a positive relationship with the profitability of firms. However, the significance of estimated coefficients was mixed and varied among different selected Asia–Pacific economies.Practical implicationsThe study has economic implications on issues such as industrial concentration, risk and optimum size of firms for practicing managers of modern enterprise in emerging markets.Originality/valueThe analysis of the relationship between the firm size, growth and profitability is uniquely determined under a dynamic panel fixed effects framework using firm-specific variables along with macroeconomic and financial development determinants of profitability. This relationship is estimated for a large and new data set of 12 industrial and emerging Asia–Pacific economies.
How firms strategically navigate informal and formal copyright practices: insights from Nollywood
Authors: Uzo Uchenna , Mair Johanna , Adewusi Adedeji 
Published: August 2021

Purpose
The purpose of this study is to explain how and why firms configure copyright practices when confronted with state-sanctioned laws and informal customs projected by local ethnic or religious communities.

Design/methodology/approach
A multi-case inductive study of four film-producing organizations within the Nigerian film industry (i.e. Nollywood) was conducted. Specifically considered were firms that started their operations around the same time with similar founding conditions, experiences, resources and technical competencies. Field observations and multiple rounds of in-depth interviews were conducted to achieve the research objectives.

Findings
The study found that firms adopted dominant or hybrid configurations when interacting with informality and formality. Dominant configurations represent the exclusive adoption of informal copyright practices while hybrid configurations refer to the blended use of informal and formal copyright practices. The second set of findings revealed that each firm’s strategic intent affected the type of interactional configuration that unfolded in the firm. Specifically, firms with social intents tended to adopt dominant configurations, whereas firms with socio-economic intents tended to adopt hybrid configurations.

Practical implications
The study implies that firms may profit from strategically focusing on when and in what circumstances to adopt informality. Strategic intents that blend social and economic rationales may secure more positive interactive outcomes from internal and external stakeholders promoting formality and informality.

Social implications
This study highlights the fact that firms embedded in local religious and ethnic communities use organizational practices to solve social and institutional problems of their members. The copyright practices of these organizations encourage apprenticeship, youth empowerment and entrepreneurship in Nigeria.

Originality/value
To the best of the authors’ knowledge, this is the first study that goes beyond macro-level analysis to investigate the interactional dynamics between formality and informality at the firm, community, and state levels. The study is also first of its kind to use copyright practices as an analytical lens to explore the interaction between informality and formality.
Don’t be a waster! Student perceptions of recycling strategies at an English University’s halls of residence
Authors: Dixon Joseph , Parker Jonathan 
Published: August 2021

Purpose
This paper aims to explore student perceptions of recycling and explore whether one university’s strategy helped or hindered student recycling in their university's halls of residence. There is near-universal acknowledgement of the urgency of the climate crisis, yet household recycling rates remain low at 45.2%. Student-recycling rates have been suggested to be even lower. After a brief consideration of the recent history of sustainability and recycling, this paper identifies the actions required to increase student recycling, including peer influence, education and information, physical structures and attitudes and motivations.

Design/methodology/approach
Twelve in-depth, semi-structured interviews were undertaken at one Southern English university. The rich, qualitative data obtained were then analysed thematically. The theory of environmentally significant behaviour provided a framework for understanding perceptions and behaviours in that site.

Findings
Confirming aspects of existing literature, students’ recycling behaviours were found to be limited through lack of perceived ability, lack of facilities and unconfident knowledge. Students were also found to be limiting their own actions. A holistic approach including peer influence, education and information, physical structures and attitudes and motivations was recommended.

Originality/value
There is little research into student recycling behaviours and limited literature concerning halls of residence, especially in the UK. This paper draws on one case to add to nascent understandings. While limited to one site and by sample size, a number of recommendations are made, covering university facilities, student empowerment and individual responsibility to increase future recycling.
Environmental service-learning approach in higher education – a descriptive case study on student-led life cycle assessments of university cafeteria meals
Authors: Johannisson Jonas , Hiete Michael 
Published: August 2021

PurposeThis study aims to share experiences of an easy to adapt service-learning approach in a graduate course on life cycle assessment (LCA). Specifically, it reports on how students helped the university’s cafeteria to assess meals by conducting an LCA for 25 meals and identifying environmental hotspots.Design/methodology/approachA descriptive case study of a graduate course at Ulm University is presented. The course included lectures and problem-based exercises, both theoretical and software assisted. A course evaluation was conducted during the course and one year after completion to poll improvement potentials, as well as its impacts on students’ everyday life.FindingsIt was found that although it was the first LCA for all students, the resulting LCA information of 25 different meals were homogeneous, comparable to the scientific literature and beneficial to the cafeteria’s sustainable development strategy. The concept of service-learning had a higher impact on students’ motivation than a good grade and active-learning is explicitly requested by students. The course design sensitized students to the real-life problems of LCA and made their consumption patterns more elaborate and ecological. Furthermore, this digitization of higher education could be carried out with only minor changes in the present COVID-19 pandemic situation.Originality/valueAs the subject of service-learning in natural sciences is still expandable, this study presents an easy to adapt case study on how to integrate such an approach into university curricula dominated by traditional learning. To the best of the authors’ knowledge, this case study presents the first published LCA university course explicitly describing and evaluating a service-learning approach. The topic touches the everyday lives of students, allows comparisons between different student groups, is easily scalable to different group sizes and credits, and supports learning both how to study in small groups and cooperation between groups to ensure comparability of LCA results.
Triggering changes in corporate governance: before and after external whistleblowing
Authors: Smaili Nadia , Arroyo Paulina 
Published: August 2021

Purpose
The purpose of this paper is to investigate whether a change of corporate governance occurs after financial crimes in Canada revealed through external whistleblowing.

Design/methodology/approach
Based on the methodology of Smaili and Arroyo (2019), the authors implement a qualitative research framework to examine 11 alleged Canadian corporate financial statement fraud cases publicly exposed during the 1995–2012 period.

Findings
The analysis suggests that firms had a weak traditional corporate governance mechanism before the external whistleblowing occurred. In almost every case, the chief executive officer (CEO) was also the chair of the board of directors. Although the reports by Dey and Saucier recommend that independent directors make up at least 75% of Canadian boards, we note that the percentage of independent directors was under 70% in six cases. Moreover, only two firms had a whistleblowing policy in place, and seven firms had a major shareholder. Regarding the consequences for corporate governance after whistleblowing, the analysis shows that the companies that survived the whistleblowing had enhanced their internal corporate governance by the third year after the whistleblowing. In fact, at all the surviving companies, the CEO was no longer the chair, and the percentage of independent directors had increased to 80%. However, for those survival companies that did not have a whistleblowing policy before the event, the situation did not change quickly, and they only implemented a policy after the enforcement of the new regulation in the year 2003.

Originality/value
This paper adds new insights to the research on financial crime by investigating the relation between corporate governance and whistleblowing.