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The search for cell-permeable drugs has conventionally focused on low-molecular weight (MW), nonpolar, rigid chemical structures. However, emerging therapeutic strategies break traditional drug design rules by employing flexibly linked chemical entities composed of more than one ligand. Using complementary genome-scale chemical-genetic approaches we identified an endogenous chemical uptake pathway involving interferon-induced transmembrane proteins (IFITMs) that modulates the cell permeability of a prototypical biopic inhibitor of MTOR (RapaLink-1, MW: 1784 g/mol). We devised additional linked inhibitors targeting BCR-ABL1 (DasatiLink-1, MW: 1518 g/mol) and EIF4A1 (BisRoc-1, MW: 1466 g/mol), uptake of which was facilitated by IFITMs. We also found that IFITMs moderately assisted some proteolysis-targeting chimeras and examined the physicochemical requirements for involvement of this uptake pathway.

Traumatic brain injury (TBI) disproportionately affects marginalized populations social workers serve. Current practices and training needs of social workers who serve clients with TBI are not well-understood. An online survey was administered to all licensed social workers in Washington (N=5,032) to assess the following for clients with TBI: interactions, challenges, knowledge, beliefs, confidence, and training recommendations. Analyses involved descriptive statistics, logistic regression, and content analysis of open-ended responses. Respondents (n=834, 16.6% response rate) endorsed serving clients with TBI, heterogeneous confidence and practices, limited training, and high learning needs. New training approaches are needed to prepare social workers to better provide services to these clients. Training on diagnosis, understanding comorbidities, treating behavioral symptoms, disparities, and advocacy tools are recommended.

In the realm of socioenvironmental justice, much discourse centers on equal access to green areas and on climate injustice in the United States. Marginalized communities, including Indigenous populations, are being excluded from current narratives surrounding the natural spaces that in many cases are historically tied to under-represented groups. This article aims to explore some of the many dimensions of environmental racism, green inequities, climate injustice, and access. The dimensions include but are not limited to racial gatekeeping, nature deprivation in low-income communities, green gentrification, light pollution, and access to clean water. The recommendations section serves as a guide during decisionmaking processes at the local, state, and federal level, as well as moving forward in offering impacted communities protection from environmental racism and socioenvironmental injustice to impacted communities.

Conservation hatcheries designed to aid in recovery of imperiled fish population often implement atypical rearing and release strategies. We evaluated a conservation hatchery program for steelhead (Oncorhynchus mykiss) that hydraulically removed naturally spawned eggs and captively reared them in different freshwater hatcheries to the smolt stage and reared smolts in both fresh water and seawater to sexual maturity, before releasing the sexually maturing adults onto the spawning grounds. The adult steelhead added to the spawning population, accounting for most of the adults observed during snorkel observations. They produced 32% of the juvenile offspring sampled, and females were 2.9 times more successful than males. Reproductive success was positively correlated with female body size, which was influenced by pre-smolt and post-smolt rearing conditions and their effects on growth rate and age-at-maturity. Juvenile offspring of the released adults showed size and age differences from offspring of naturally returning steelhead, but exhibited very similar early marine survival rates. Les ecloseries de conservation concues pour soutenir le retablissement de populations de poissons en peril adoptent souvent des strategies atypiques d'elevage et de lacher. Nous avons evalue un programme d'ecloseries de conservation pour le saumon arc-en-ciel (Oncorhynchus mykiss) dans le cadre duquel des oeufs pondus naturellement ont ete preleves de maniere hydraulique et eleves en captivite dans differentes ecloseries en eau douce jusqu'au stade de smolt, puis les smolts ont ete eleves jusqu'a maturite sexuelle en eau douce et en eau de mer, les adultes a maturite sexuelle etant ensuite relaches sur les frayeres. Ces saumons arc-en-ciel adultes se sont ajoutes a la population reproductrice, constituant la plupart des adultes observes durant des releves en plongee en apnee. Ils ont produit 32 % de la progeniture juvenile echantillonnee, le succes de reproduction des femelles etant 2,9 fois plus grand que celui des males. Le succes de reproduction etait positivement correle a la taille du corps des femelles, qui etait influencee par les conditions d'elevage pre- et post-smoltification et leurs effets sur le taux de croissance et l'age a la maturite. La progeniture juvenile des adultes relaches presentait des differences de taille et d'age par rapport a la progeniture de saumons arc-en-ciel revenus naturellement, mais des taux de survie precoce en mer tres semblables. [Traduit par la Redaction], Introduction Captive breeding and rearing programs have been implemented for a broad diversity of freshwater and anadromous fish species at high risk of extinction (Ireland et al. 2002; Pollard and [...]

Food insecurity and poor infant and young child feeding (IYCF) practices contribute to undernutrition. The Kanyakla Nutrition Program was developed in rural Kenya to provide knowledge alongside social support for recommended IYCF practices. Utilizing a social network approach, the Kanyakla Nutrition Program trained community health workers (CHWs) to engage mothers, fathers, and grandparents in nutrition education and discussions about strategies to provide instrumental, emotional, and information support within their community. The 12-week programme included six sessions and was implemented on Mfangano Island, Kenya, in 2014-2015. We analysed intervention effects on (a) nutrition knowledge among community members or CHWs and (2) IYCF practices among children 1-3 years. Nutrition knowledge was assessed using a postintervention comparison among intervention (community, n = 43; CHW, n = 22) and comparison groups (community, n = 149; CHW, n = 64). We used a quasi-experimental design and difference-in-difference to assess IYCF indicators using dietary recall data from an ongoing cohort study among intervention participants (n = 48) with individuals living on Mfangano Island where the intervention was not implemented (n = 178) before the intervention, within 1 month postintervention, and 6 months postintervention. Findings showed no effect of the intervention on IYCF indicators (e.g., dietary diversity and meal frequency), and less than 15% of children met minimum acceptable diet criteria at any time point. However, knowledge and confidence among community members and CHWs were significantly higher 2 years postintervention. Thus, a social network approach had an enduring effect on nutrition knowledge, but no effects on improved IYCF practices.

Background: Current return to learn (RTL) after concussion guidelines lack specificity for individualized student care, limiting potential for adoption and implementation. We used a community-engaged research framework to develop and evaluate the implementation of a student-centered care plan that assists school personnel in facilitating RTL. Methods: We used best-practice RTL guidelines and input from administrators and medical experts to iteratively develop a flexible student-centered care plan. Thirteen schools participated. Coding completion of care plans indicated feasibility and fidelity; interviews with RTL coordinators indicated acceptability. Results: The care plan includes educational materials, symptom checklists, and guidelines for classroom adjustments linked to student symptoms. Care plans were initiated for 24 (70.6%) of 34 students with concussions, indicating feasibility. Fidelity was high, with the following subsections completed: Action Checklist (90%), Symptom Evaluation (91%), Temporary Adjustment Recommendations (95%). Qualitative analysis of interviews suggested care plans were acceptable and facilitate consistent communication, prioritization of individual needs of students, and increased ability to delegate tasks to other school staff. Conclusions: Implementation of a student-centered, individually tailored care plan for RTL is feasible and acceptable in public high schools. Future research should examine how to expediently initiate student-centered concussion care plans after diagnosis to optimize recovery.

DEAD-box proteins are an essential class of enzymes involved in all stages of RNA metabolism. The study of DEAD-box proteins is challenging in a native setting since they are structurally similar, often essential and display dosage sensitivity. Pharmacological inhibition would be an ideal tool to probe the function of these enzymes. In this work, we describe a chemical genetic strategy for the specific inactivation of individual DEAD-box proteins with small molecule inhibitors using covalent complementarity. We identify a residue of low conservation within the P-loop of the nucleotide-binding site of DEAD-box proteins and show that it can be mutated to cysteine without a substantial loss of enzyme function to generate electrophile-sensitive mutants. We then present a series of small molecules that rapidly and specifically bind and inhibit electrophile-sensitive DEAD-box proteins with high selectivity over the wild-type enzyme. Thus, this approach can be used to systematically generate small molecule-sensitive alleles of DEAD-box proteins, allowing for pharmacological inhibition and functional characterization of members of this enzyme family.