Secondary Coordination Sphere Alkylation Promotes Cyclometalation.

Diphosphines have taken on a dominant role as supporting ligands in transition-metal chemistry. Here, we describe complexes of the type [Cp*Fe(diphosphine)(X)] (X = Cl, H) where for diphosphine = 1,2-bis(di-allylphosphino)ethane (tape), a Lewis-acidic secondary coordination sphere (SCS) was installed via allyl group hydroboration using dicyclohexylborane (HBCy2). The resulting chloride complex, [Cp*Fe(P2BCy4)(Cl)] (P2BCy4 = 1,2-bis(di(3-cyclohexylboranyl)propylphosphino)ethane), was treated with n-butyllithium (1-10 equiv), resulting incyclometalation at iron. This reactivity is contrasted with [Cp*Fe(dnppe)(Cl)] (dnppe = 1,2-bis(di-n-propylphosphino)ethane), whereby addition of n-butyllithium provides a mixture of products. Overall, cyclometalation is a common elementary transformation in organometallic chemistry; here we describe how this outcome is accessed in response to Lewis acid SCS incorporation.

Bis(1-bora-4-phosphorinane) ring closure at Cp*M (M = Fe, Co) complexes.

Bis(1-bora-4-phosphorinane) metal complexes have been synthesized using a Cp*M-protecting (M = FeIICl, CoI, Cp* = C5Me5-) strategy and structurally authenticated by NMR spectroscopy and single crystal X-ray diffraction. Synthesis of these scaffolds is highly sensitive to the identity of vinylphosphine precursor. This approach provides a new method for the generation of saturated P,B-containing main-group ring systems.

Increasing Racial and Ethnic Diversity in Occupational Therapy Education: The Role of Accreditation Council for Occupational Therapy Education (ACOTE®) Standards.

Now more than ever, the lack of racial and ethnic diversity must be addressed within the health care system, specifically in occupational therapy. This change starts with the successful completion of educational programs by underrepresented minority (URM) occupational therapy students. To increase diversity in the profession, accrediting bodies should mandate support for students of all backgrounds to be successful in higher education. As addressed in the American Occupational Therapy Association 2020 Code of Ethics, the Vision 2025 statement and its pillars, current knowledge on health disparities and occupational therapy demographic data, and other health professional programs' accreditation standards, there is a need for an addition to, or revision of, the Accreditation Council for Occupational Therapy Education (ACOTE®) standards to support the recruitment and retention of URM occupational therapy students. What This Article Adds: This column provides an evidence-based rationale to address the need for an ACOTE standard requiring documented efforts to support racial and ethnic diversity within occupational therapy education.

MAGP2 controls Notch via interactions with RGD binding integrins: Identification of a novel ECM-integrin-Notch signaling axis.

Canonical Notch signaling involves Notch receptor activation via interaction with cell surface bound Notch ligand. Recent findings also indicate that Notch signaling may be modulated by cross-talk with other signaling mechanisms. The ECM protein MAGP2 was previously shown to regulate Notch in a cell type dependent manner, although the molecular details of this interaction have not been dissected. Here, we report that MAGP2 cell type specific control of Notch is independent of individual Notch receptor-ligand combinations but dependent on interaction with RGD binding integrins. Overexpressed MAGP2 was found to suppress transcriptional activity from the Notch responsive Hes1 promoter activity in endothelial cells, while overexpression of a RGD→RGE MAGP2 mutant increased Notch signaling in the same cell type. This effect was not unique to MAGP2 since the RGD domain of the ECM protein EGFL7 was also found to be an important modulator of Hes1 promoter activity. Independently of MAGP2 or EGFL7, inhibition of RGD-binding integrins with soluble RGD peptides also increased accumulation of active N1ICD fragments and Notch responsive promoter activity independently of changes in Notch1, Jag1, or Dll4 expression. Finally, ß1 or ß3 integrin blocking antibodies also enhanced Notch signaling. Collectively, these results answer the question of how MAGP2 controls cell type dependent Notch signaling, but more importantly uncover a new mechanism to understand how extracellular matrices and cellular environments impact Notch signaling.

Nutri-epigenetics ameliorates blood-brain barrier damage and neurodegeneration in hyperhomocysteinemia: role of folic acid.

Epigenetic mechanisms underlying nutrition (nutrition epigenetics) are important in understanding human health. Nutritional supplements, for example folic acid, a cofactor in one-carbon metabolism, regulate epigenetic alterations and may play an important role in the maintenance of neuronal integrity. Folic acid also ameliorates hyperhomocysteinemia, which is a consequence of elevated levels of homocysteine. Hyperhomocysteinemia induces oxidative stress that may epigenetically mediate cerebrovascular remodeling and leads to neurodegeneration; however, the mechanisms behind such alterations remain unclear. Therefore, the present study was designed to observe the protective effects of folic acid against hyperhomocysteinemia-induced epigenetic and molecular alterations leading to neurotoxic cascades. To test this hypothesis, we employed 8-weeks-old male wild-type (WT) cystathionine-beta-synthase heterozygote knockout methionine-fed (CBS+/− + Met), WT, and CBS+/− + Met mice supplemented with folic acid (FA) [WT + FA and CBS+/− + Met + FA, respectively, 0.0057-µg g−1 day−1 dose in drinking water/4 weeks]. Hyperhomocysteinemia in CBS+/− + Met mouse brain was accompanied by a decrease in methylenetetrahydrofolate reductase and an increase in S-adenosylhomocysteine hydrolase expression, symptoms of oxidative stress, upregulation of DNA methyltransferases, rise in matrix metalloproteinases, a drop in the tissue inhibitors of metalloproteinases, decreased expression of tight junction proteins, increased permeability of the blood-brain barrier, neurodegeneration, and synaptotoxicity. Supplementation of folic acid to CBS+/− + Met mouse brain led to a decrease in the homocysteine level and rescued pathogenic and epigenetic alterations, showing its protective efficacy against homocysteine-induced neurotoxicity.

Indigenous and immigrant populations' use and experience of community pharmacies in New Zealand.

We sought to identify what services indigenous (Maori) and immigrant populations use pharmacies for, and how long pharmacy staff spend interacting with them, as longer interactions are associated with better quality care. We review literature on counseling in pharmacy, and interaction length as an indicator of counseling quality. 1,086 interactions were discretely observed in 36 pharmacies in 5 cities around New Zealand. Maori or Pacific people, along with men, were more likely to treat pharmacies as prescription 'depots', being less likely to buy over-the-counter or pharmacist only medicines (ORs: 0.25-0.72). However, the influence of demographic factors on interaction length was small (|B|s < 7.7 s). The weak effect of ethnicity on interaction length suggests that pharmacies are providing advice of relatively consistent quality to different population groups. Possible barriers to use of pharmacies for primary healthcare, including over-the-counter medicines in Maori and Pacific people are discussed.