Structural basis for the constitutive activity and immunomodulatory properties of the Epstein-Barr virus-encoded G protein-coupled receptor BILF1

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The identification of the UV degradants of melatonin and their ability to scavenge free radicals

Ultraviolet (UV) light is known to induce the generation of free radicals in biological tissues such as skin. Of these free radicals, the O2-. and particularly the.OH radical can induce cellular damage including lipid peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV irradiation has received much attention recently. One such antioxidant, which has the potential to be incorporated into sunscreens, is the pineal secretory product melatonin. One of the concerns of using melatonin in sunscreens is its photostability. In the present study, we investigated the photostability of melatonin subjected to UV irradiation. In addition, we used liquid chromatography mass spectrometry (LC-MS) to identify the degradants and we also assessed the ability of the degradants to inhibit O2-. generation as well as lipid peroxidation in rat brain homogenate. The results show that UV irradiation of melatonin (0.1 mg/mL) using a 400-W lamp for 2 hr caused a significant decline of melatonin to 18% of its original concentration after 20 min, with the decline continuing until the melatonin concentration reaches zero at 120 min. The LC-MS results show that the degradants of melatonin are 6-hydroxymelatonin and N1-acetyl-N2-formyl-5-methoxykynurenamine (AFMK). These degradants were able to provide equipotent activity against potassium cyanide (KCN)-induced superoxide generation compared to non-irradiated melatonin. Thus, the study shows that although melatonin is rapidly degraded by UV irradiation, the degradants retain antioxidant activity, making melatonin a likely candidate for inclusion in sunscreens.     

Anchor residues in protein-protein interactions

We show that the mechanism for molecular recognition requires one of the interacting proteins, usually the smaller of the two, to anchor a specific side chain in a structurally constrained binding groove of the other protein, providing a steric constraint that helps to stabilize a native-like bound intermediate. We identify the anchor residues in 39 protein-protein complexes and verify that, even in the absence of their interacting partners, the anchor side chains are found in conformations similar to those observed in the bound complex. These ready-made recognition motifs correspond to surface side chains that bury the largest solvent-accessible surface area after forming the complex (> or =100 A2). The existence of such anchors implies that binding pathways can avoid kinetically costly structural rearrangements at the core of the binding interface, allowing for a relatively smooth recognition process. Once anchors are docked, an induced fit process further contributes to forming the final high-affinity complex. This later stage involves flexible (solvent-exposed) side chains that latch to the encounter complex in the periphery of the binding pocket. Our results suggest that the evolutionary conservation of anchor side chains applies to the actual structure that these residues assume before the encounter complex and not just to their loci. Implications for protein docking are also discussed.     

Associations Between Abortion Services and Acceptance of Postabortion Contraception in Six Indian States

Women receiving induced abortions or postabortion care are at high risk of subsequent unintended pregnancy, and intervals of less than six months between abortion and subsequent pregnancy may be associated with adverse outcomes. This study highlights the prevalence and attributes of postabortion contraceptive acceptance from 2,456 health facilities in six major Indian states, among 292,508 women who received abortion care services from July 2011 through June 2014. Eighty‐one percent of the women accepted postabortion contraceptive methods: 53 percent short‐term, 11 percent intrauterine devices, and 16 percent sterilization. Postabortion contraceptive acceptance was highest among women who were aged 25 years and older, received first‐trimester services, received induced abortion, attended primary‐level health facilities, and had medical abortions. Doctors receiving post‐training support were more likely to offer contraceptives, but no association was observed between such support and acceptance of IUDs or sterilization. Comprehensive service‐delivery interventions, including ensuring availability of skilled providers and contraceptive commodities, offering clinical mentoring for providers, identifying and addressing provider bias, and improving provider counseling skills, can increase postabortion contraceptive acceptance and reduce unintended pregnancy.