Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.

Cells adapt to temperature shifts by adjusting levels of lipid desaturation and membrane fluidity. This fundamental process occurs in nearly all forms of life, but its mechanism in eukaryotes is unknown. We discovered that the evolutionarily conserved Caenorhabditis elegans gene acdh-11 (acyl-CoA dehydrogenase [ACDH]) facilitates heat adaptation by regulating the lipid desaturase FAT-7. Human ACDH deficiency causes the most common inherited disorders of fatty acid oxidation, with syndromes that are exacerbated by hyperthermia. Heat upregulates acdh-11 expression to decrease fat-7 expression. We solved the high-resolution crystal structure of ACDH-11 and established the molecular basis of its selective and high-affinity binding to C11/C12-chain fatty acids. ACDH-11 sequesters C11/C12-chain fatty acids and prevents these fatty acids from activating nuclear hormone receptors and driving fat-7 expression. Thus, the ACDH-11 pathway drives heat adaptation by linking temperature shifts to regulation of lipid desaturase levels and membrane fluidity via an unprecedented mode of fatty acid signaling.

Pragmatic Emergency Department Intervention Reducing Default Quantity of Opioid Tablets Prescribed.

Introduction: The opioid epidemic is a major cause of morbidity and mortality in the United States. Prior work has shown that emergency department (ED) opioid prescribing can increase the incidence of opioid use disorder in a dose-dependent manner, and systemic changes that decrease default quantity of discharge opioid tablets in the electronic health record (EHR) can impact prescribing practices. However, ED leadership may be interested in the impact of communication around the intervention as well as whether the intervention may differentially impact different types of clinicians (physicians, physician assistants [PA], and nurse practitioners). We implemented and evaluated a quality improvement intervention of an announced decrease in EHR default quantities of commonly prescribed opioids at a large, academic, urban, tertiary-care ED. Methods: We gathered EHR data on all ED discharges with opioid prescriptions from January 1, 2019-December 6, 2021, including chief complaint, clinician, and opioid prescription details. Data was captured and analyzed on a monthly basis throughout this time period. On March 29, 2021, we implemented an announced decrease in EHR default dispense quantities from 20 tablets to 12 tablets for commonly prescribed opioids. We measured pre- and post-intervention quantities of opioid tablets prescribed per discharge receiving opioids, distribution by patient demographics, and inter-clinician variability in prescribing behavior. Results: The EHR change was associated with a 14% decrease in quantity of opioid tablets per discharge receiving opioids, from 14 to 12 tablets (P = <.001). We found no statistically significant disparities in prescriptions based on self-reported patient race (P = 0.68) or gender (P = 0.65). Nurse practitioners and PAs prescribed more opioids per encounter than physicians on average and had a statistically significant decrease in opioid prescriptions associated with the EHR change. Physicians had a lesser but still significant drop in opioid prescribing in the post-intervention period. Conclusion: Decreasing EHR defaults is a robust, simple tool for decreasing opioid prescriptions, with potential for implementation in the 42% of EDs nationwide that have defaults exceeding the recommended 12-tablet supply. Considering significant inter-clinician variability, future interventions to decrease opioid prescriptions should examine the effects of combining EHR default changes with targeted interventions for clinician groups or individual clinicians.

Age-related positivity enhancement is not universal: older Chinese look away from positive stimuli.

Socioemotional selectivity theory postulates that with age, people are motivated to derive emotional meaning from life, leading them to pay more attention to positive relative to negative/neutral stimuli. The authors argue that cultures that differ in what they consider to be emotionally meaningful may show this preference to different extents. Using eye-tracking techniques, the authors compared visual attention toward emotional (happy, fearful, sad, and angry) and neutral facial expressions among 46 younger and 57 older Hong Kong Chinese. In contrast to prior Western findings, older but not younger Chinese looked away from happy facial expressions, suggesting that they do not show attentional preferences toward positive stimuli.

A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs.

Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems.

Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo.

Chronic skin ulcerations are a common complication of diabetes mellitus, affecting up to one in four diabetic individuals. Despite the prevalence of these wounds, current pharmacologic options for treating them remain limited. Growth factor-based therapies have displayed a mixed ability to drive successful healing, which may be due to nonoptimal delivery strategies. Here, a method for coating commercially available nylon dressings using the layer-by-layer process is described to enable both sustained release and independent control over the release kinetics of vascular endothelial growth factor 165 and platelet-derived growth factor BB. It is shown that the use of strategically spaced diffusion barriers formed spontaneously by disulfide bonds enables independent control over the release rates of incorporated growth factors, and that in vivo these dressings improve several aspects of wound healing in db/db mice.

Interdependent self-construal moderates the age-related negativity reduction effect in memory and visual attention.

There is some debate concerning whether people selectively attend to and remember less negative relative to positive or neutral information with age. We argue that such an age-related negativity reduction effect may be attenuated among individuals who are more interdependent, as they are likely to perceive negative information as equally useful and important as positive information. In 2 studies, we tested this hypothesis by examining memory for (Study 1) and visual attention to (Study 2) emotional (positive vs. negative) stimuli among younger, middle-aged, and older Chinese participants. Findings revealed that the age-related negativity reduction effect was found to a lesser extent among older Chinese individuals who were more interdependent than among those who were less interdependent.