Campus Safety: Assessing and Managing Threats

Since the shootings at Virginia Tech, academic institutions and police departments have dedicated substantial resources to alleviating concerns regarding campus safety. The incident in Blacksburg and the similar tragedy at Northern Illinois University have brought renewed attention to the prevention of violence at colleges and universities. Campus professionals must assess the risk posed by known individuals, as well as by anonymous writers of threatening communications. The authors offer threat assessment and management strategies to address the increased demands faced by campus law enforcement, mental health, and administration officials who assess and manage threats, perhaps several simultaneously

Dislocation and degradation from the ER are regulated by cytosolic stress

Akey step in ER-associated degradation (ERAD) is dislocation of the substrate protein from the ER into the cytosol to gain access to the proteasome. Very little is known about how this process is regulated, especially in the case of polytopic proteins. Using pulse-chase analysis combined with subcellular fractionation, we show that connexins, the four transmembrane structural components of gap junctions, can be chased in an intact form from the ER membrane into the cytosol of proteasome inhibitor–treated cells. Dislocation of endogenously expressed connexin from the ER was reduced 50–80% when the cytosolic heat shock response was induced by mild oxidative or thermal stress, but not by treatments that instead upregulate the ER unfolded protein response. Cytosolic but not ER stresses slowed the normally rapid degradation of connexins, and led to a striking increase in gap junction formation and function in otherwise assembly-inefficient cell types. These treatments also inhibited the dislocation and turnover of a connexin-unrelated ERAD substrate, unassembled major histocompatibility complex class I heavy chain. Our findings demonstrate that dislocation is negatively regulated by physiologically relevant, nonlethal stress. They also reveal a previously unrecognized relationship between cytosolic stress and intercellular communication

Intracellular Transport, Assembly, and Degradation of Wild-Type and Disease-linked Mutant Gap Junction Proteins

More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot–Marie–Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To address these issues, we have studied the intracellular transport, assembly, and degradation of three CMTX-linked Cx32 mutants stably expressed in PC12 cells. Each mutant had a distinct fate: E208K Cx32 appeared to be retained in the endoplasmic reticulum (ER), whereas both the E186K and R142W mutants were transported to perinuclear compartments from which they trafficked either to lysosomes (R142W Cx32) or back to the ER (E186K Cx32). Despite these differences, each mutant was soluble in nonionic detergent but unable to assemble into homomeric connexons. Degradation of both mutant and wild-type connexins was rapid (t1/2 \u3c 3 h) and took place at least in part in the ER by a process sensitive to proteasome inhibitors. The mutants studied are therefore unlikely to cause disease by accumulating in degradation-resistant aggregates but instead are efficiently cleared from the cell by quality control processes that prevent abnormal connexin molecules from traversing the secretory pathway

Evaluation at Sunset: Considerations When Evaluating a Program as It Concludes

While the benefits of beginning evaluation efforts at a program’s inception are well known, for a variety of reasons many organizations are unable to do so and instead begin these efforts closer to a program’s conclusion. Previously reported findings from a sunset evaluation of the Orfalea Foundation’s School Food Initiative showed positive outcomes of the initiative’s activities and provided recommendations for organizations interested in engaging in similar efforts. Because the evaluation was begun as the foundation’s activities were winding down, it required creative design approaches. This article uses the evaluation of the Orfalea Foundation’s initiative to provide a case example of a rigorous and useful sunset evaluation, and discusses other possible extensions of these kinds of methods

Key Ingredients for School Food Systems: An Evaluation of the Orfalea Foundation’s School Food Initiative

In 2007, the Orfalea Foundation launched a nine-year strategic effort aimed at empowering public school districts in California’s Santa Barbara County. The purpose was to implement food-service operations that offered nourishing meals and to create a culture that prioritized the health and wellness of children and families. The initiative, which involved 84 schools and more than 50,000 students, assessed the capacity of the county’s school food services, including existing skill levels and equipment needs. Striving to tailor programming to specific needs, the foundation emphasized stakeholder involvement throughout the process. The foundation took a number of steps to understand the value and impact of the initiative, including working with Evaluation Specialists, an outside evaluator. This article shares best practices and lessons learned with organizations interested in learning from and replicating the initiative’s efforts, and with policymakers and school districts interested in improving school food

COMMUNITY AND NETWORK RESPONSES FOR ASSISTING MOBILE VULNERABLE POPULATIONS

The COVID-19 crisis highlighted the increasing vulnerability of individuals, households, and communities. It has almost certainly been even more devastating for those who rely on community networks and organizations for aid but are less able to access aid networks in conditions of reduced mobility. This is the case for “mobile vulnerable populations,” among which include persons experiencing homelessness, victims of human trafficking,immigrants, refugees, and Latinos/as. This report summarizes our research with local Omaha service providers about what they need to serve mobile vulnerable populations in the community, how the pandemic has affected their ability to do so, and whether there have been any substantial and/or institutionalized partnerships between UNO/UNMC and these community organizations. In our research, we used a multi-method approach consisting of a survey of community organization leaders and interviews with organization workers engaged into day-to-day service provision to meet the needs of their clients. Our findingscan be summarized in four main themes: (a) organizations were already under-resourced prior to the pandemic; (b) the impact of the COVID-19 pandemic on organizations was substantial; (c) organizations described similar strengths and innovative responses to the pandemic; and (d) there is a lack of institutionalized collaboration with UNO/UNMC. We argue that building connections between UNO/UNMC and community organizations, as well as assisting in the development of networks among various organizations, is central to the mission of the University of Nebraska system and could benefitthe community more broadly. Concluding, we present four main recommendations: (1) more connections are needed between UNO/UNMC and agencies in the Omaha area; (2) it is likely that there are existing relationships between agency partners and UNO/UNMC faculty, staff and students that could be leveraged; (3) there is an opportunity to prepare students and emphasize workforce growth among providers; and (4) the important work of serving mobile vulnerable populations can be rewarding but also challenging for Omaha providers

Neogenin-mediated hemojuvelin shedding occurs after hemojuvelin traffics to the plamsa membrane

Hemochromatosis type 2 gene (HFE2) is highly expressed in skeletal muscle and liver hepatocytes. Its encoded protein, hemojuvelin (HJV), is a co-receptor for the bone morphogenetic proteins 2 and 4 (BMP2 and BMP4) and enhances the BMP-induced hepcidin expression. Hepcidin is a central iron regulatory hormone predominantly secreted from hepatocytes. HJV also binds neogenin, a membrane protein widely expressed in many tissues. Neogenin is required for the processing and release of HJV from cells. The role that neogenin plays in HJV trafficking was investigated, using HepG2 cells, a human hepatoma cell line. Knockdown of endogenous neogenin markedly suppresses HJV release, but has no evident effect on HJV trafficking to the plasma membrane. Addition of a soluble neogenin ectodomain to cells markedly inhibits HJV release, indicating that the HJV shedding is not processed before trafficking to the cell surface. At the plasma membrane it undergoes endocytosis in a dynamin-independent but cholesterol-dependent manner. The additional findings that HJV release is coupled to lysosomal degradation of neogenin, that HJV undergoes endocytosis, and that cholesterol depletion by filipin blocks both HJV endocytosis and HJV release, suggest that neogenin-mediated HJV release occurs after the HJV-neogenin complex is internalized from the cell surface