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Social and emotional learning (SEL) is seldom explicitly considered in science-based higher education (HE), yet we argue that group-based lab learning both requires and facilitates the development of valuable interpersonal and emotional skills. This study focuses on Year 1 and Year 2 Biomedical Science undergraduates working in groups to undertake an innovative, discovery-based laboratory module. It explores students’ perceptions of how emotions impact science discovery learning and whether and how they used and developed social and emotional skills in this learning context. We draw together theories that explain the development of emotional intelligence and how people influence each other’s emotions, and apply them to an HE context. Data were collected using questionnaires and semi-structured interviews, and analysis identified three key themes: situated and social emotion in the lab, awareness of interpersonal emotional influence, and SEL as experiential and relational. These give insight into the subtle yet powerful ways that students work with emotion in the process of collaborative discovery learning. We identify successful strategies and challenges, and make recommendations for embedding SEL in Science, Technology, Engineering, and Mathematics (STEM) HE settings. These include approaches to integrate context-relevant emotional skill development, both explicitly and implicitly, and nurture peer emotional scaffolding.

The paracrine properties of human amniotic membrane‐derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC‐CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC‐CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC‐CM by cytokine array. Our results strongly support the concept that the administration of hAMC‐CM favors the repair process after acute myocardial infarction. The goal of this study was to elucidate whether human amniotic membrane‐derived mesenchymal stromal cells (hAMCs) can exert beneficial paracrine effects on infarcted rat hearts. In particular, the administration of hAMC‐conditioned medium repaired ischemic damage through cardioprotection and angiogenesis. Finally, several putative active paracrine mediators that might account for the effects observed were identified by gene and protein arrays.

Anti‐inflammatory and immune‐modulatory therapies have been proposed for the treatment of COVID‐19 and its most serious complications. Among others, the use of mesenchymal stromal cells (MSCs) is under investigation given their well‐documented anti‐inflammatory and immunomodulatory properties. However, some critical issues regarding the possibility that MSCs could be infected by the virus have been raised. Angiotensin‐converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2), entry, but so far it is unclear if human MSCs do or do not express these two proteins. To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS‐CoV‐2. We evaluated human MSCs derived from amnios, cord blood, cord tissue, adipose tissue, and bone marrow. ACE2 and TMPRSS2 were expressed by the SARS‐CoV‐2‐permissive human pulmonary Calu‐3 cell line but not by all the MSCs tested. MSCs were then exposed to SARS‐CoV‐2 wild strain without evidence of cytopathic effect. Moreover, we also excluded that the MSCs could be infected without showing lytic effects since their conditioned medium after SARS‐CoV‐2 exposure did not contain viral particles. Our data, demonstrating that MSCs derived from different human tissues are not permissive to SARS‐CoV‐2 infection, support the safety of MSCs as potential therapy for COVID‐19. SARS‐CoV‐2 enters into host cells through ACE2 and TMPRSS2. Mesenchymal stromal cells (MSCs) derived from amnios (A), cord blood (CB), cord tissue (CT), adipose tissue (AT) and bone marrow (BM) do not express these proteins, as demonstrated by RT‐qPCR, western blot, ELISA and immunofuorescence. They are not infected by either spike pseudovirus, or by SARS‐CoV‐2 wild strain.

OPCML , a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers. OPCML is a tumour suppressor gene that is epigenetically silenced in ovarian cancer and is somatically mutated in various cancers. Here, the authors solve the X-ray crystal structure of OPCML and model clinically relevant mutations that could contribute to tumorigenesis.

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that some ERVs are used by the host as restriction factors to block the infection of pathogenic retroviruses. Indeed, some ERVs efficiently interfere with the replication of related exogenous retroviruses. However, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model system to study retrovirus-host coevolution because of the coexistence in this animal species of two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, Jaagsiekte sheep retrovirus and Enzootic nasal tumor virus, with highly related and biologically active endogenous retroviruses (enJSRVs). Here, we isolated and characterized the evolutionary history and molecular virology of 27 enJSRV proviruses. enJSRVs have been integrating in the host genome for the last 5-7 million y. Two enJSRV proviruses (enJS56A1 and enJSRV-20), which entered the host genome within the last 3 million y (before and during speciation within the genus Ovis), acquired in two temporally distinct events a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses. Both transdominant proviruses became fixed in the host genome before or around sheep domestication (approximately 9,000 y ago). Interestingly, a provirus escaping the transdominant enJSRVs has emerged very recently, most likely within the last 200 y. Thus, we determined sequentially distinct events during evolution that are indicative of an evolutionary antagonism between endogenous and exogenous retroviruses. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections.

The sheep genome harbors ≈20 copies of endogenous retroviruses (enJSRVs) closely related to the exogenous and oncogenic Jaagsiekte sheep retrovirus (JSRV). One of the enJSRV loci, enJS56A1, has a defect for viral exit. We report a previously uncharacterized mechanism of retroviral interference. The defect possessed by enJS56A1 is determined by its Gag protein and is transdominant over the exogenous JSRV. By electron microscopy, cells transfected by enJS56A1, with or without JSRV, show agglomerates of tightly packed intracellular particles most abundant in the perinuclear area. The defect in exit and ability to interfere with JSRV exit could be largely attributed to the presence of tryptophan, rather than arginine, at position 21 of enJS56A1 Gag; C98 and V102 also contribute to these properties. We found that enJS56A1 or similar loci containing W21, C98, and V102 are expressed in sheep endometrium. enJS56A1 is a previously unrecognized example of a naturally occurring endogenous retrovirus expressing a dominant negative Gag acting at a late step of the viral replication cycle. Understanding the late blockade exerted by enJS56A1 could unravel fundamental aspects of retroviral biology and help to devise new antiretroviral strategies.

Aurein 2.6-COOH and aurein 3.1-COOH were studied along with their naturally occurring C-terminally amidated analogues. Circular dichroism (CD) and molecular dynamic (MD) simulations were used to study the effects of amidation on the interaction of antimicrobial peptides (AMPs) with lipid bilayers. CD measurements and MD analysis suggested that both peptide analogues were predominantly random coil and adopted low levels of α -helical structure in solution (<30 %) and in the presence of a lipid bilayer the peptides formed a stable α -helical structure. In general, amidated analogues have a greater propensity than the non-amidated peptides to form a α -helical structure. MD simulations predicted that aurein 2.6-COOH and aurein 3.1-CHOOH destabilised lipid bilayers from 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphoserine via angled bilayer penetration. They also showed that aurein 2.6-CONH 2 and aurein 3.1-CONH 2 formed a helix horizontal to the plane of an asymmetric interface.

The 2015–16 Zika virus epidemic emerged in the Americas and rapidly spread throughout the region and beyond, showing the epidemic potential of this mosquito-borne Orthoflavivirus and its capacity to cause severe congenital malformations and neurological sequelae. WHO declared the Zika virus epidemic a public health emergency of international concern in 2016. Despite this declaration, there are no licensed Zika virus vaccines, therapeutics, or diagnostic tests appropriate for routine antenatal screening. To address this absence of essential tools to detect and mitigate the threat of future Zika virus outbreaks, a group of global experts developed a priority agenda for Zika virus research and development. This Series paper summarises crucial challenges and knowledge gaps and outlines a comprehensive strategy to advance research, surveillance, global capacity, policy, and investment for Zika virus preparedness and response.

West Nile virus (WNV) is a neurotropic mosquito-borne virus that re-emerged in the last 25 years to cause substantial short- and long-term morbidity and mortality, particularly in the United States and Europe. Attempts to mitigate the impact of WNV by vector control have been largely unsuccessful. A WNV vaccine could be effective in decreasing disease burden. To identify and address important barriers to licensing human WNV vaccines, U.S. Centers for Disease Control and Prevention convened a meeting of key stakeholders from the U.S. federal and municipal governments, industry, academia, and regulatory agencies in April 2024. Topics discussed included epidemiology, impact of outbreaks, rationale for human vaccines, animal models and correlates of protection, diagnostic considerations, candidate human vaccines in clinical development, and regulatory considerations for vaccine development. Several barriers to human WNV vaccine licensure were identified, including 1) episodic transmission with substantial geographic and temporal variability in disease occurrence impeding the feasibility of phase III clinical trials evaluating vaccine efficacy against WNV disease, 2) high asymptomatic attack rate affecting potential clinical trial endpoint considerations, 3) lack of a surrogate endpoint to predict clinical benefit, 4) need for standardized reagents and assays to quantitate antibodies, and 5) minimal economic support for vaccine development and commercial manufacturing. Future activities to support advancing WNV vaccine development and licensure involve developing a target product profile, establishing suitable animal models and surrogate endpoints to predict clinical benefit, developing a diagnostic test to differentiate immunologic response to infection versus vaccination, conducting a sales forecast analysis, exploring partnerships that could advance vaccine development and licensure, and considering alternative approaches for licensure such as the accelerated approval pathway. We need to work collaboratively as a public health and scientific community to ensure human vaccines are available to decrease the ongoing morbidity and mortality caused by WNV.

The 2015–16 Zika virus epidemic in the Americas drew global attention to Zika virus infection as a cause of microcephaly and Guillain–Barré syndrome. The epidemic highlighted the urgent need for preventive measures, including vaccines and monoclonal antibodies (mAbs). However, nearly 9 years later, no licensed Zika virus vaccines or mAbs are available, leaving the world's populations unprotected from ongoing disease transmission and future epidemics. The current low Zika virus incidence and unpredictability of future outbreaks complicates prospects for evaluation, licensure, and commercial viability of Zika virus vaccines and mAbs. We conducted an extensive review of Zika virus vaccines and mAbs in development, identifying 16 vaccines in phase 1 or phase 2 trials and three mAbs in phase 1 trials, and convened a 2-day meeting of 130 global Zika virus experts to discuss research priorities to advance their development. This Series paper summarises a priority research agenda to address key knowledge gaps and accelerate the licensure of Zika virus vaccines and mAbs for global use.