bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype
Authors: Barut Tuba , Halwe Nico Joel , Taddeo Adriano , Kelly Jenna N. , Schön Jacob , Ebert Nadine , Ulrich Lorenz , Devisme Christelle , Steiner Silvio , Trüeb Bettina Salome , Hoffmann Bernd , Veiga Inês Berenguer , Leborgne Nathan Georges François , Moreira Etori Aguiar , Breithaupt Angele , Wylezich Claudia , Höper Dirk , Wernike Kerstin , Godel Aurélie , Thomann Lisa , Flück Vera , Stalder Hanspeter , Brügger Melanie , Esteves Blandina I. Oliveira , Zumkehr Beatrice , Beilleau Guillaume , Kratzel Annika , Schmied Kimberly , Ochsenbein Sarah , Lang Reto M. , Wider Manon , Machahua Carlos , Dorn Patrick , Marti Thomas M. , Funke-Chambour Manuela , Rauch Andri , Widera Marek , Ciesek Sandra , Dijkman Ronald , Hoffmann Donata , Alves Marco P. , Benarafa Charaf , Beer Martin , Thiel Volker 
Published: April 2022

AbstractVariant of concern (VOC) Omicron-BA1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization of Omicron-BA.1 in advanced primary cell culture systems and multiple animal models is urgently needed. Here, we characterized Omicron-BA.1 and recombinant Omicron-BA.1 spike gene mutants in comparison with VOC Delta in well-differentiated primary human nasal and bronchial epithelial cells in vitro, followed by in vivo fitness characterization in naïve hamsters, ferrets and hACE2-expressing mice, and in immunized hACE2-mice. We demonstrate a spike-mediated enhancement of early replication of Omicron-BA.1 in nasal epithelial cultures, but limited replication in bronchial epithelial cultures. In Syrian hamsters, Delta showed dominance over Omicron-BA.1 and in ferrets, Omicron-BA.1 infection was abortive. In mice expressing the authentic hACE2-receptor, Delta and a Delta spike clone also showed dominance over Omicron-BA.1 and an Omicron-BA.1 spike clone, respectively. Interestingly, in naïve K18-hACE2 mice, we observed Delta spike-mediated increased replication and pathogenicity and Omicron-BA.1 spike-mediated reduced replication and pathogenicity, suggesting that the spike gene is a major determinant of both Delta and Omicron-BA.1 replication and pathogenicity. Finally, the Omicron-BA.1 spike clone was less well controlled by mRNA-vaccination in K18-hACE2-mice and became more competitive compared to the progenitor and Delta spike clones, suggesting that spike gene-mediated immune evasion is another important factor that led to Omicron-BA.1 dominance.
ST6GAL1 sialyltransferase promotes acinar to ductal metaplasia and pancreatic cancer progression
Authors: Chakraborty Asmi , Bhalerao Nikita , Marciel Michael P. , Hwang Jihye , Britain Colleen M. , Eltoum Isam E. , Jones Robert B. , Alexander Katie L. , Smythies Lesley E. , Smith Phillip D. , Crossman David K. , Crowley Michael R. , Shin Boyoung , Harrington Laurie E. , Yan Zhaoqi , Bethea Maigen M. , Hunter Chad S. , Klug Christopher A. , Buchsbaum Donald J. , Bellis Susan L. 
Published: April 2022

AbstractThe role of aberrant glycosylation in pancreatic ductal adenocarcinoma (PDAC) remains an under-investigated area of research. In this study, we determined that the ST6GAL1 sialyltransferase, which adds α2,6-linked sialic acids to N-glycosylated proteins, is upregulated in patients with early-stage PDAC, and further increased in advanced disease. A tumor-promoting function for ST6GAL1 was elucidated using tumor xenograft models with human PDAC cells. Additionally, we developed a genetically-engineered mouse (GEM) with transgenic expression of ST6GAL1 in the pancreas, and found that mice with dual expression of ST6GAL1 and oncogenic KRASG12D have greatly accelerated PDAC progression and mortality compared with mice expressing KRASG12D alone. As ST6GAL1 imparts progenitor-like characteristics, we interrogated ST6GAL1’s role in acinar to ductal metaplasia (ADM), a process that fosters neoplasia by reprogramming acinar cells into ductal, progenitor-like cells. We confirmed that ST6GAL1 promotes ADM using multiple models including the 266-6 cell line, GEM-derived organoids and tissues, and an in vivo model of inflammation-induced ADM. EGFR is a key driver of ADM and is known to be activated by ST6GAL1-mediated sialylation. Importantly, EGFR activation was dramatically increased in acinar cells and organoids from mice with transgenic ST6GAL1 expression. These collective results highlight a novel glycosylation-dependent mechanism involved in early stages of pancreatic neoplasia.
Sensory regulation of absence seizures in a mouse model of Gnb1 encephalopathy
Authors: Teng Sasa , Zhen Fenghua , McRae Briana R. , Zhu Elaine , Frankel Wayne N. , Peng Yueqing 
Published: April 2022

SUMMARYAbsence seizures, a type of non-convulsive epilepsy manifested by spike-wave discharges (SWD) in the electroencephalogram (EEG), display synchronous reciprocal excitation between the neocortex and thalamus. Recent studies have revealed that inhibitory neurons in the reticular thalamic (RT) nucleus and excitatory thalamocortical (TC) neurons are two key subcortical players in generating SWD. However, the signals that drive SWD-related thalamic activity remain elusive. Here, we show that SWD predominately occurs during wakefulness in several mouse models of absence epilepsy. In more focused studies of Gnb1 mutant mice, we found that sensory input regulates SWD. Using in vivo recording, we demonstrate that TC cells are activated prior to the onset of SWD and then inhibited during SWD. On the contrary, RT cells are slightly inhibited prior to SWD, but are strongly activated during SWD. Furthermore, chemogenetic activation of TC cells leads to the enhancement of SWD in Gnb1 mice. Together, our results indicate that sensory input in the periphery can regulate SWD by activating the thalamocortical pathway.
An auto-inhibited state of protein kinase G and implications for selective activation
Authors: Sharma Rajesh , Kim Jeong Joo , Qin Liying , Henning Philipp , Akimoto Madoka , VanSchouwen Bryan , Kaur Gundeep , Sankaran Banumathi , MacKenzie Kevin R. , Melacini Giuseppe , Casteel Darren E. , Herberg Friedrich W. , Kim Choel 
Published: April 2022

AbstractCyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cGMP signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Campaigns targeting nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis suggest that understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation by cGMP is still not well understood. Here we present a crystal structure of PKG Iβ in which the auto-inhibitory sequence and the cyclic nucleotide binding domains are bound to the catalytic domain, providing a snapshot of the auto-inhibited state. Specific contacts between the PKG Iβ auto-inhibitory sequence and the enzyme active site help explain isoform-specific activation constants and the effects of phosphorylation in the linker. We also present a crystal structure of a PKG I cyclic nucleotide binding domain with an activating mutation linked to Thoracic Aortic Aneurysms and Dissections. Similarity of this structure to wild type cGMP-bound domains and differences with the auto-inhibited enzyme provide a mechanistic basis for constitutive activation. We show that PKG Iβ auto-inhibition is mediated by contacts within each monomer of the native full-length dimeric protein, and using the available structural and biochemical data we develop a model for the regulation and activation of PKGs.
Molecular Characterization of the Tumor Microenvironment in Renal Medullary Carcinoma
Authors: Tourigny David S. , Zucker Mark , Kim Minsoo , Russo Paul , Coleman Jonathan , Lee Chung-Han , Carlo Maria I. , Chen Ying-Bei , Hakimi A. Ari , Kotecha Ritesh R. , Reznik Ed 
Published: April 2022

AbstractRenal medullary carcinoma (RMC) is a highly aggressive disease associated with sickle hemoglobinopathies and universal loss of the tumor suppressor gene SMARCB1. RMC has a relatively low rate of incidence compared with other renal cell carcinomas (RCCs) that has hitherto made molecular profiling difficult. To probe this rare disease in detail we performed an in-depth characterization of the RMC tumor microenvironment using a combination of genomic, metabolic and single-cell RNA-sequencing experiments on tissue from a representative untreated RMC patient, complemented by retrospective analyses of archival tissue and existing published data. Our study of the tumor identifies a heterogenous population of malignant cell states originating from the thick ascending limb of the Loop of Henle within the renal medulla, displaying the hallmarks of increased resistance to cell death by ferroptosis and proteotoxic stress driven by MYC-induced proliferative signals. Specifically, genomic characterization of RMC tumors provides substantiating evidence for the recently proposed dependence of SMARCB1-difficient cancers on an intact CDKN2A-p53 pathway and we suggest increased cystine-mTORC-GPX4 signaling also plays a role within transformed RMC cells. We further propose that RMC has an immune landscape comparable to that of untreated RCCs, including heterogenous expression of the immune ligand CD70 within a sub-population of tumor cells, which could provide an immune-modulatory role that serves as a viable candidate for therapeutic targeting.
Human anelloviruses produced by recombinant expression of synthetic genomes
Authors: Nawandar Dhananjay M. , Trivedi Maitri , Bounoutas George , Lebo Kevin , Prince Cato , Scano Colin , Agarwal Nidhi , Ozturk Erin , Yu Jason , Arze Cesar A. , Bhattacharyya Agamoni , Verma Dinesh , Thakker Parmi , Cabral Joseph , Liou Shu-Hao , Swanson Kurt , Swaminathan Harish , Diaz Fernando , Mackey Ashley , Chang Yong , Ong Tuyen , Yozwiak Nathan L. , Hajjar Roger J. , Delagrave Simon 
Published: April 2022

ABSTRACTHuman anelloviruses are acquired universally in infancy, highly prevalent, abundant in blood, and extremely diverse. Their apparent lack of pathogenicity indicates that they are a major component of the commensal human virome. Despite their being extensively intertwined with human biology, these viruses are poorly understood. A major impediment in studying anelloviruses is the lack of an in vitro system for their production and/ or propagation. Here we show that the T cell-derived human cell line MOLT-4 can be transfected with plasmids comprising tandem anellovirus genomes to produce viral particles visualized by electron microscopy. We found that a previously described human anellovirus of the Betatorquevirus genus (LY2), as well as a second Betatorquevirus detected by sequencing DNA extracted from a human retinal pigmental epithelium (nrVL4619), can be synthesized and produced by these means, enabling further molecular virology studies. Southern blot was used to demonstrate replication, and site-directed mutagenesis of the viral genome was performed to show that the production of anellovirus in this cell line is dependent on the expression of certain viral proteins. Finally, experiments performed in mice using purified nrVL4619 particles produced in MOLT-4 cells demonstrated infectivity in vivo in the tissue of origin. These results indicate that anelloviruses can be produced in vitro and manipulated to improve our understanding of this viral family which is ubiquitous in humans and many other mammals. Applications of this work to gene therapy and other therapeutic modalities are currently under investigation.IMPORTANCEAnelloviruses are a major component of the human virome. However, their biology is not well understood mainly due to the lack of an in vitro system for anellovirus production and/or propagation. In this study, we used multiple orthogonal measures to show that two different anelloviruses belonging to the Betatorquevirus genus can be produced in a T-cell-derived human cell line, MOLT-4, via recombinant expression of synthetic genomes. Additionally, we show that anellovirus particles generated in this in vitro system demonstrate infectivity in vivo. Our findings enable new molecular virology studies of this highly prevalent, non-pathogenic, and weakly immunogenic family of viruses, potentially leading to therapeutic applications.
Compassion‐focused therapy group for men with intellectual disabilities who had maladaptive conceptualisations of masculinity
Authors: Searle Robert John , Borseti Ianiv , Price Katy-May 
Published: April 2022

Purpose
The purpose of this paper is to determine the effectiveness of an adapted compassion-focused therapy (CFT) group treatment programme for individuals with an intellectual disability (ID), specifically aimed to help address maladaptive conceptualisations of masculinity.

Design/methodology/approach
Outcome measurements were competed at pre- and post-group and the effectiveness of the intervention were assessed using a Wilcoxon signed ranks test.

Findings
Findings demonstrated that the treatment group showed significant differences in their “gender role conflict” subscales including the Success, Power, Control and “Restrictive Affectionate Behavior Between Men” subscales; however, no significant differences were found on the Restrictive Emotionality or Conflicts Between Work and Leisure subscales. Furthermore, no significant differences were found on participants psychological well-being, psychological distress, anxiety, self-compassion or quality of life measures.

Research limitations/implications
Limitations include that a lack of qualitative information regarding outcomes, a lack of control group and a small number of participants may have impacted the outcome of the research.

Practical implications
The Men’s Masculinity group had a positive impact on the participant’s sense of success, power and control, so it could be considered that this group enabled participants to feel more powerful and in control of their difficulties which is associated with the “drive” system of CFT.

Originality/value
Overall, this study adds to the small but growing literature that supports using CFT groups as a stand-alone psychological intervention when working with people with an ID.
A systematic review of indicators for sustainability of urban heritage sites
Authors: Cho Ken Ying , Kusumo Camelia May Li , Tan Keith Kay Hin , Rasoolimanesh S. Mostafa 
Published: April 2022

PurposeThe revitalisation of tangible and intangible urban heritage can foster social cohesion and drive creativity and innovation in a changing global environment. Recognising its potential for economic development, many local municipalities are putting forward efforts to revitalise these areas. However, this has caused these sites to face new pressures, such as gentrification, demographic shifts and commercial exploitation. Therefore, a sustainable redevelopment of urban heritage sites that strikes a balance between the economic, environmental and social dimensions is needed. To plan and manage this balance, a strong and clear indicator to measure the sustainability of urban heritage is required. The study systematically reviewed through Scopus indexed journals the dimensions to develop sustainable indicators of urban heritage sites and highlighted the gaps for future research. It identified the existing studies and explored publications, research methods, challenges and suggestions to develop the indicators.Design/methodology/approachThe study applied Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 Statement. The Boolean search was in Scopus indexed journals for papers related to indicators in sustainable urban heritage sites.FindingsMost of the literature highlighted the interconnected relationships between the indicators for the sustainability of urban heritage sites: social, economic and environmental dimensions. It further revealed that for a more robust management of sustainable monitoring tools, it is crucial to include governance dimensions. Plus, technology is the intertwined aspect for the four dimensions, with culture identified as the centre for sustainability of urban heritage sites.Research limitations/implicationsThe paper only focused on secondary data using literature review papers that recommend gaps for future research. Possible future research includes alternative, niche literature reviews and the implementation of indicators in regional urban heritage sites.Originality/valueIt created a new insight into the dimensions recommended to develop sustainable indicators for urban heritage sites.
Rurbanomics for common prosperity: new approach to integrated urban-rural development
Authors: Chen Kevin Z. , Mao Rui , Zhou Yunyi 
Published: April 2022

PurposeChallenges from the urban–rural disparity immensely burden the world's progress fulfilling Sustainable Development Goals and the goals' central promise, particularly for developing countries experiencing rapid structural change and urbanization. A knowledge gap lies between the epistemology of urban–rural disparity and the practice of integrated urban-rural development. This paper aims to provide a new approach to bridge the knowledge gap based on the recent Chinese experience.Design/methodology/approachThis qualitative research reviewed major economic and multidisciplinary studies regarding urban-rural development and the growth-equality tradeoff. Chinese experience is employed to showcase concrete challenges from the urban–rural disparity and how the proposed approach works for urban-rural integration.FindingsTheoretical and practical approaches with urban bias largely fail to counter the challenges. Building on China's recent practice probing beyond urban bias, IFPRI (2019) proposes the term rurbanomics with a highlight of equalized urban-rural economic partnership, whereafter Zhou and Chen (2021) enrich the term into a conceptual framework. This paper further improves rurbanomics as a new viable approach to integrated urban-rural development under the overarching goal of common prosperity. The approach prioritizes driving forces in the economic, demographic, eco-environmental, social institutional and technological aspects for the policy community to leverage. Long-term mechanisms are decerned to link urban-rural integration to common prosperity.Practical implicationsChina has leveraged ingredients of the rurbanomics approach in the political deployment to integrated urban-rural development. However, the application of this approach is yet to be adapted with local heterogeneities and live up to application's potential. Long-term mechanisms recommended by the rurbanomics approach will need to be carried out. Future improvements will need substantial theoretical extension and micro-level empirical studies.Originality/valueThis paper streamlines the epistemological shreds regarding pursuits, challenges, global experiences and theoretical approaches of urban-rural development. The paper also develops rurbanomics to navigate urban-rural integration, Sustainable Development Goals and common prosperity. By decerning long-term mechanisms in the Chinese case accordingly, this paper provides clues for other economies to employ the new approach.
Do independent boards pay attention to corporate sustainability? Gender diversity can make a difference
Authors: Kanadlı Sadi Boğaç , Alawadi Asma , Kakabadse Nada , Zhang Pingying 
Published: April 2022

Purpose
Using the attention-based view, this paper aims to examine whether and how board composition might influence the allocation of board attention to corporate sustainability.

Design/methodology/approach
This is a conceptual paper that uses a theoretical perspective pointing to the importance of generating a board composition that might benefit both business case framing and paradoxical framing, a typology introduced in managerial cognition literature to explain managerial decision-making.

Findings
The conclusions emerging from the reviewed literature suggest that boards that have realized an independence of perspective focus on shareholder profit maximization at the expense of considerations of corporate sustainability. It emerges that women directors who have adopted paradoxical framing can enable boards to consider not only economic but also environmental and social issues of sustainability during board decision-making. Further, it is noted that the effect of gender diversity on allocation of board attention to corporate sustainability is contingent upon contextual (board openness) and structural (chairperson leadership) factors that facilitate social interactions inside boardrooms.

Originality/value
By considering alternative cognitive frames as well as social interactions, the propositions contribute to a better understanding of the allocation of board attention regarding ambiguous sustainability issues.
Review of public–private partnerships across building sectors in nine European countries: Key adaptations for PPP in housing
Authors: Batra Ritika 
Published: April 2022

PurposeThis paper aims to review the existing practices of public–private partnerships (PPPs) in the building sectors in European countries, to be able to assess its suitability for housing provision while focussing on the social impact.Design/methodology/approachBased on the sectoral spread of PPP, nine European countries were included in this study. Formative evaluation is used to structure the review based on four key attributes of PPPs to develop a comprehensive understanding of the existing PPP procedures and guidelines amongst these countries. Data were gathered through public and governmental reports, consultant reports, country guidelines, standards and procedures, and cases, in order to identify the prevalent practices and trends in these countries.FindingsThe review identified the need to calibrate the PPP approach towards other stakeholders, particularly the end-users. It further highlighted the need to focus on social integration and social sustainability and establish set procedures for PPPs in housing to create a credible and trustworthy environment for the investors. Joint support from private and public partners and community participation has a diverse impact on the success of PPP in housing.Practical implicationsThis review shall enable governments, industry and stakeholders to make provisions and policies for overcoming the challenges identified with regard to PPPs and pave the way for its application in the housing sector ensuring a positive social impact.Social implicationsThis review shall facilitate greater involvement of end-users and enhancing social integration in housing through PPP, and pave the way towards creating cohesive communities by focussing on the concept of togetherness and social sustainability.Originality/valueThis study provides a holistic summation of the prevalent PPP practices and broadens the adaptations for the housing sector. The novelty of this paper specifically lies in learning from PPP practices across other building sectors for adapting its utilisation for housing and thereby extending the state of art for PPP housing.