SNAP-25 is expressed in neurons and endocrine cells and is essential for exocytosis of neurotransmitters and peptide hormones. It has been shown to be involved in several interactions with other ...proteins of the secretion machinery. Here we show that SNAP-25 can self-associate to form a disulfide-linked complex. Complex formation is facilitated in vitro (in concentrated extracts or by immunoprecipitation). SNAP-25 complexes, however, also form when intact cells are treated with a membrane-permeable crosslinker indicating that SNAP-25 molecules exist in close proximity in vivo and could form complexes spontaneously. We also show that monomeric SNAP-25 and disulfide-linked SNAP-25 complexes are palmitoylated and that both can be cleaved by botulinum neurotoxin E.
Distribution of oral iodized oil capsules (IOC) is an important intervention in areas with iodine deficiency disorders (IDD) and low coverage of iodized salt. The mean reported coverage of 57 IOC ...distribution campaigns from 1986-1994 of people aged 1-45 years in 27 districts of Tanzania was 64% (range 20-96%). This declined over subsequent distribution rounds. However, due to delayed repeat distribution, only 43% of person-time was covered, based on the programme objective of giving two IOC (total 400 mg iodine) at 2-year intervals. Three different capsule distribution strategies used in 20 distribution rounds in 1992-1993 were analyzed in depth. Withdrawal of financial support for district distribution expenses under the 'district team' strategy, and the subsequent change to integrated 'primary health care' distribution, increased delays and capsule wastage. The third, more vertical strategy, 'national and district teams', accomplished rapid distribution of IOC about to expire and subsequently a return to the initial 'district team' allowance strategy was made. Annual cost of 'district team' distribution was 26 cents per person (400 mg iodine/2 years). Cost analysis revealed that the IOC itself accounts for more than 90% of total costs at the levels of coverage achieved. IOC will be important in the elimination of IDD in target areas of severe iodine deficiency and insufficient use of iodized salt, provided that high coverage can be achieved. Campaign distribution of medication with high item cost and long distribution intervals may be more cost-effectively performed if separated from regular PHC services at their present resource level. However, motivating health workers and community leaders to do adequate social mobilization remains crucial even if logistics are vertically organized. Insufficient support of distribution expenses and health education may lead to overall wastage of resources.
In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a ...modified dialysis method using an albumin‐containing dialysate that is recirculated and perfused online through charcoal and anion‐exchanger columns. MARS enables the selective removal of albumin‐bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30‐day survival in patients with type I HRS at high risk (bilirubin level, ≥15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child‐Turcotte‐Pugh scores of 12.4 ± 1.0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 ± 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 ± 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P< .01) and increase in serum sodium level and prothrombin activity (P< .01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P< .01). We conclude that the removal of albumin‐bound substances with the MARS method can contribute to the treatment of type I HRS.
The semimetal MoTe\(_2\) is studied by spin- and angle- resolved photoemission spectroscopy to probe the detailed electronic structure underlying its broad range of response behavior. A novel ...spin-texture is uncovered in the bulk Fermi surface of the non-centrosymmetric structural phase that is consistent with first-principles calculations. The spin-texture is three-dimensional, both in terms of momentum dependence and spin-orientation, and is not completely suppressed above the centrosymmetry-breaking transition temperature. Two types of surface Fermi arc are found to persist well above the transition temperature. The appearance of a large Fermi arc depends strongly on thermal history, and the electron quasiparticle lifetimes are greatly enhanced in the initial cooling. The results indicate that polar instability with strong electron-lattice interactions exists near the surface when the bulk is largely in a centrosymmetric phase.
The structures of novel oligoglycosidic cardenolides, alepposide A (C55H86O23) 1 and alepposide B (C48H74O20) 2, have been deduced mainly by nmr methods. Based on homonuclear (1H and 13C nmr, 1H ...COSY) and proton-detected heteronuclear shift correlation experiments HMQC both for 1J(C,H) and for long-range couplings, alepposide A 1 was shown to have the structure strophanthidin-3-O-beta-glucopyranosyl-(1-->4)-O-beta-diginopyranosyl -(1-->4)-O - beta-oleandropyranosyl-(1-->4)-O-beta-digitoxopyranosyl-(1-- >4)-O-beta- digitoxopyranoside. The structure of alepposide B 2 was established as strophanthidin-3-O-beta-glucopyranosyl-(1-->4)-O-beta-oleandropyranos yl- (1-->4)-O-beta-digitoxopyranosyl-(1-->4)-O-beta-digitoxopyranos ide.
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