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Swine acute diarrhea syndrome coronavirus (SADS-CoV) was reported in China in 2017 and is a causative agent of porcine enteric disease. Recent studies indicate that cells from various hosts are susceptible to SADS-CoV, suggesting the zoonotic potential of this virus. However, little is known about the mechanisms through which this virus enters cells. In this study, we investigated the role of furin in SADS-CoV spike (S)-mediated cell – cell fusion and entry. We found that the SADS-CoV S protein induced the fusion of various cells. Cell – cell fusion was inhibited by the proprotein convertase inhibitor dec-RVKR-cmk, and between cells transfected with mutant S proteins resistant to furin cleavage. These findings revealed that furin-induced cleavage of the SADS-CoV S protein is required for cell – cell fusion. Using mutagenesis analysis, we demonstrated that furin cleaves the SADS-CoV S protein near the S1/S2 cleavage site, 446RYVR449 and 543AVRR546. We used pseudotyped viruses to determine whether furin-induced S cleavage is also required for viral entry. Pseudotyped viruses expressing S proteins with a mutated furin cleavage site could be transduced into target cells, indicating that furin-induced cleavage is not required for pseudotyped virus entry. Our data indicate that S cleavage is critical for SADS-CoV S-mediated cell – cell fusion and suggest that furin might be a host target for SADS-CoV antivirals.

Abstract Purpose The disruption of undergraduate medical education (UME) by the COVID-19 pandemic has sparked rapid, real-time adjustments by medical educators and students. While much is known about online teaching in general, little guidance is available to medical educators on how to adapt courses not originally designed for the online environment. To guide our faculty in this transition we conducted a needs assessment of students enrolled in virtual courses across all 4 years of UME training. Methods Using a mixed-methods approach, we conducted a single-institution virtual learning needs assessment in May and June of 2020. We developed and disseminated a survey to assess student experiences with virtual learning. We conducted quantitative and qualitative analysis of responses (n = 255 or 39%) to identify emergent themes. Results We identified six interdependent themes that need to be met for medical students to fully reach their learning potential: access to stable internet and quiet study spaces, flexible course design with asynchronous, self-paced components, clear expectations for engagement with content and each other, a sense of connectedness with faculty and peers, synchronous classes that maximize interactivity, and assessments that foster a sense of learning over performance. Interpersonal relationships with faculty and peers affected students’ sense of learning more than any other factor. Conclusions Based on our findings we propose a hierarchy of needs for virtual learning that provides guidance on adapting existing medical school courses to the remote setting and overcoming common challenges. We highlight opportunities for how virtual elements may enrich in-person courses going forward, including in the clinical setting. Although the solutions required to meet the threshold of need at each level may differ based on the context, attending to these same fundamental needs can be extrapolated and applied to learners across a range of environments beyond the virtual.

Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, using a murine thymic slice model in which thymocytes undergo negative selection in situ, we demonstrate that phagocytosis promotes negative selection, and provide evidence for the escape of autoreactive CD8 T cells to the periphery when phagocytosis in the thymus is impaired. We also show that negative selection is more efficient when the phagocyte also presents the negative selecting peptide. Our findings support a model for negative selection in which the death process initiated following strong TCR signaling is facilitated by phagocytosis. Thus, the phagocytic capability of cells that present self-peptides is a key determinant of thymocyte fate.

Porcine epidemic diarrhea (PED), a highly contagious and lethal enteric disease in piglets, is characterized by diarrhea, vomiting, and dehydration, with high mortality in neonatal piglets. Despite the nationwide use of attenuated and inactivated vaccines, the outbreak of PED is still a major problem in the swine industry. Virus-like particles (VLPs) are artificial nanoparticles similar to viruses that are devoid of genetic material and are unable to replicate. VLPs have good safety profiles and elicit robust cellular and humoral immune responses. Here, we generated PED VLPs in eukaryotic cells and examined their immune responses in mice. We found that the M protein is essential for the formation of PED VLPs. Interestingly, PED VLP formation was decreased in the presence of E proteins and increased in the presence of N proteins. Both IgG and IgA antibodies were induced in mice immunized with PED VLPs. Moreover, these antibodies protected against PED virus infection in Vero cells. PED VLPs immunization induced Th2-dominant immune responses in mice. Our results indicate that PED VLPs induce strong immune responses in mice, suggesting that the VLP-based vaccine is a promising vaccine candidate.

Abstract Anisotropically compartmentalized microparticles have attracted increasing interest in areas ranging from sensing, drug delivery, and catalysis to microactuators. Herein, a facile method is reported for the preparation of helically decorated microbuilding blocks, using a modified electrohydrodynamic cojetting method. Bicompartmental microfibers are twisted in situ, during electrojetting, resulting in helical microfibers. Subsequent cryosectioning of aligned fiber bundles provides access to helically decorated microcylinders. The unique helical structure endows the microfibers/microcylinders with several novel functions such as translational motion in response to rotating magnetic fields. Finally, microspheres with helically patterned compartments are obtained after interfacially driven shape shifting of helically decorated microcylinders.

In nine studies using archival data, surveys, and experiments, we identify a factor that predicts gender differences in time stress and burnout. Across academic and professional settings, women are less likely to ask for more time when working under adjustable deadlines (studies 1 to 4a). Women's discomfort in asking for more time on adjustable deadlines uniquely predicts time stress and burnout, controlling for marital status, industry, tenure, and delegation preferences (study 1). Women are less likely to ask for more time to complete their tasks because they hold stronger beliefs that they will be penalized for these requests and worry more about burdening others (studies 1 to 2d). We find no evidence that women are judged more harshly than men (study 3). We also document a simple organizational intervention: formal processes for requesting deadline extensions reduce gender differences in asking for more time (studies 4a to 5). [ABSTRACT FROM AUTHOR]

Polydiacetylenes (PDAs) and the electrospinning technique are used to fabricate a litumus-type chemosensor for volatile organic compounds (VOCs). This led to the development of a novel colorimetric sensor system based on silica-enforced electrospun microfibers embedded with conjugated polymers.

Polymer particles with controlled internal architecture are currently under development for a number of emerging applications. In compartmentalized particles, well-defined pockets of distinct materials can be designed that can give rise to a set of orthogonal (i.e., dissimilar) properties within the same particle. While this aspect appears crucial, when multifunctional particles for sensing, imaging or drug delivery are sought after, their experimental realization has only recently been explored in broader terms. In this review, we highlight current progress related to the design and fabrication of multicompartmental particles and discuss potential benefits and experimental challenges associated with different synthetic routes. [ABSTRACT FROM AUTHOR]