Feeding during hibernation shifts gene expression toward active season levels in brown bears (Ursus arctos).

Hibernation in bears involves a suite of metabolical and physiological changes, including the onset of insulin resistance, that are driven in part by sweeping changes in gene expression in multiple tissues. Feeding bears glucose during hibernation partially restores active season physiological phenotypes, including partial resensitization to insulin, but the molecular mechanisms underlying this transition remain poorly understood. Here, we analyze tissue-level gene expression in adipose, liver, and muscle to identify genes that respond to midhibernation glucose feeding and thus potentially drive postfeeding metabolical and physiological shifts. We show that midhibernation feeding stimulates differential expression in all analyzed tissues of hibernating bears and that a subset of these genes responds specifically by shifting expression toward levels typical of the active season. Inferences of upstream regulatory molecules potentially driving these postfeeding responses implicate peroxisome proliferator-activated receptor gamma (PPARG) and other known regulators of insulin sensitivity, providing new insight into high-level regulatory mechanisms involved in shifting metabolic phenotypes between hibernation and active states.

A multi-tissue gene expression dataset for hibernating brown bears.

OBJECTIVES: Complex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears (Ursus arctos). DATA DESCRIPTION: This dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.

Serum plays an important role in reprogramming the seasonal transcriptional profile of brown bear adipocytes.

Understanding how metabolic reprogramming happens in cells will aid the progress in the treatment of a variety of metabolic disorders. Brown bears undergo seasonal shifts in insulin sensitivity, including reversible insulin resistance in hibernation. We performed RNA-sequencing on brown bear adipocytes and proteomics on serum to identify changes possibly responsible for reversible insulin resistance. We observed dramatic transcriptional changes, which depended on both the cell and serum season of origin. Despite large changes in adipocyte gene expression, only changes in eight circulating proteins were identified as related to the seasonal shifts in insulin sensitivity, including some that have not previously been associated with glucose homeostasis. The identified serum proteins may be sufficient for shifting hibernation adipocytes to an active-like state.

Domestic Violence Risk Assessment Research to Real-World Practice: The Devil Is in the Implementation.

Assessing risk in domestic violence situations is foundational to ensuring safety. Although there is growing information about the reliability and validity of a variety of risk assessment tools across different practice contexts, there is a paucity of research on the feasibility and application of these tools in real world settings. The present qualitative study examined current practices in domestic violence risk assessment in Canada through a survey of professionals working across diverse sectors. Utilizing a thematic analysis of 255 open-text responses, this study presents several themes related to challenges identified at the systemic, organizational, and individual levels. Themes related to promising practices and the practical implication of risk assessment strategies are also explored.

The Police Role in Domestic Homicide Prevention: Lessons From a Domestic Violence Death Review Committee.

This study examined the role of police in domestic homicide cases reviewed by a multidisciplinary death review committee in Ontario, Canada. Examining the 219 domestic homicide case summaries, this study explored the difference between homicides with, and without, prior police contact. Results indicated that police contacted cases had 63% more risk factors present compared with cases without prior police contact, with 80% of police-involved cases having 10 or more risk factors. Police cases had unique risk factors present including a failure to comply with authority, access to victims after risk assessments, prior threats to kill victims (including with a weapon), history of domestic violence (DV), extreme minimization of DV, addiction concerns, and an escalation of violence. Cases involving child homicide have unique child-specific risk factors such as custody disputes, threats to children, and abuse during pregnancy. Overall, there was a lack of formal risk assessments conducted. Implications are discussed in terms of police intervention being a critical opportunity for risk assessment, safety planning, and risk management. Although there is no certainty in predicting that lives would have been saved, the level of risk presented calls for enhanced efforts at assessment and intervention for adult victims and their children.

Complexities of the Police Response to Intimate Partner Violence: Police Officers' Perspectives on the Challenges of Keeping Families Safe.

Through interviews with police officers (n = 15), the present study examined police perspectives toward their response to intimate partner violence (IPV). Qualitative analyses indicated several challenges police officers face in responding to IPV, including barriers at the systemic, organizational, and individual levels. Police officers in the current study also identified recommendations toward overcoming barriers. Overall, results continue to underscore a lack of police consistency toward addressing IPV, including inconsistent approaches to assessing and managing risk posed to families. Conversely, qualitative results point to several recommendations that heavily involve collaboration between community and justice partners. Implications for future research and practice include further examination of the identified recommendations, a continued focus on developing training that addresses the risk posed to high-risk families, and further development of collaborative approaches toward the prevention and intervention of IPV.

Selective deletion of human leukocyte antigens protects stem cell-derived islets from immune rejection.

Stem cell-based replacement therapies hold the promise to restore function of damaged or degenerated tissue such as the pancreatic islets in people with type 1 diabetes. Wide application of these therapies requires overcoming the fundamental roadblock of immune rejection. To address this issue, we use genetic engineering to create human pluripotent stem cells (hPSCs) in which the majority of the polymorphic human leukocyte antigens (HLAs), the main drivers of allogeneic rejection, are deleted. We retain the common HLA class I allele HLA-A2 and less polymorphic HLA-E/F/G to allow immune surveillance and inhibition of natural killer (NK) cells. We employ a combination of in vitro assays and humanized mouse models to demonstrate that these gene manipulations significantly reduce NK cell activity and T-cell-mediated alloimmune response against hPSC-derived islet cells. In summary, our approach produces hypoimmunogenic hPSCs that can be readily matched with recipients to avoid alloimmune rejection.

Can offsetting the energetic cost of hibernation restore an active season phenotype in grizzly bears (Ursus arctos horribilis)?

Hibernation is characterized by depression of many physiological processes. To determine if this state is reversible in a non-food caching species, we fed hibernating grizzly bears (Ursus arctos horribilis) dextrose for 10 days to replace 53% or 100% of the estimated minimum daily energetic cost of hibernation. Feeding caused serum concentrations of glycerol and ketones (ß-hydroxybutyrate) to return to active season levels irrespective of the amount of glucose fed. By contrast, free fatty acids (FFAs) and indices of metabolic rate, such as general activity, heart rate, strength of heart rate circadian rhythm, and insulin sensitivity were restored to approximately 50% of active season levels. Body temperature was unaffected by feeding. To determine the contribution of adipose to the metabolic effects observed after glucose feeding, we cultured bear adipocytes collected at the beginning and end of the feeding and performed metabolic flux analysis. We found a ∼33% increase in energy metabolism after feeding. Moreover, basal metabolism before feeding was 40% lower in hibernation cells compared with fed cells or active cells cultured at 37°C, thereby confirming the temperature independence of metabolic rate. The partial depression of circulating FFAs with feeding likely explains the incomplete restoration of insulin sensitivity and other metabolic parameters in hibernating bears. Further depression of metabolic function is likely to be an active process. Together, the results provide a highly controlled model to examine the relationship between nutrient availability and metabolism on the hibernation phenotype in bears.

Challenges in Risk Assessment with Rural Domestic Violence Victims: Implications for Practice.

Through interviews the present study examined the perspectives of service providers (n = 14) in the violence against women (VAW) sector regarding risk factors and challenges in assessing risk for women experiencing domestic violence (DV) in rural locations. The present study also examined what promising practices VAW service providers are utilizing when working with women experiencing DV in rural locations. Interviews were coded and analyzed in a qualitative analysis computer program. Analysis indicated several risk factors including the location (i.e., geographic isolation, lack of transportation, and lack of community resources) and cultural factors (i.e., accepted and more available use of firearms, poverty, and no privacy/anonymity). Moreover, analyses indicated several challenges for VAW service providers assessing risk including barriers at the systemic (i.e., lack of agreement between services), organizational (i.e., lack of collaboration and risk assessment being underutilized/valued), and individual client (i.e., complexity of issues) level. However, participants outlined promising practices being implemented for rural locations such as interagency collaboration, public education, professional education, and outreach programs. The findings support other research in the field that highlight the increased vulnerability of women experiencing DV in rural locations and the added barriers and complexities in assessing risk for rural populations. Implications for future research and practice include further examination of the identified promising practices, a continued focus on collaborative approaches and innovative ways to prevent and manage risk in a rural context.

Experiences of Intimate Partner Violence Victims With Police and the Justice System in Canada.

Legal responses to intimate partner violence (IPV) can determine whether and how those exposed to IPV seek help. Understanding the victim's perspective is essential to developing policy and practice standards, as well as informing professionals working in policing and the justice system. In this survey study, we utilized a subset of 2,831 people who reported experiencing IPV to examine (a) rates of reporting to the police; (b) experiences with, and perceived helpfulness of, police; (c) rates of involvement with the criminal and family law systems, including protection orders; and (d) experiences with, and perceived helpfulness of, the justice system. Data were analyzed using descriptive statistics for closed-ended survey questions and content analysis of text responses. More than 35% of victims reported a violent incident to the police, and perceptions of helpfulness were mixed. Fewer victims were involved with the criminal and family law systems, and their satisfaction also varied. Text responses provided insight into possible reasons for the variability found in experiences, for example, the proposed role of victim and system expectations, and respondents' perception that getting help depends on "being lucky" with the officials encountered.