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131.
    
Utilizing X-ray crystallography and molecular modeling, highly potent and selective peptidomimetic thrombin inhibitors have been designed containing a rigid piperazinedione template. The synthesis and biological activity of these compounds will be described.  相似文献   
132.
    
The DJ-1 gene is highly conserved in diverse species and DJ-1 is known as an anti-oxidative stress factor. In this study, we investigated the neuroprotective effects of DJ-1 against ischemic damage in the rabbit spinal cord. Tat-DJ-1 fusion proteins were constructed to facilitate the penetration of DJ-1 protein into the neurons. Tat-1-DJ-1 fusion protein was administered to the rabbit 30 min after ischemia/reperfusion, and transient spinal cord ischemia was induced by occlusion of the aorta at the subrenal region for 15 min. The administration of Tat-DJ-1 significantly improved the Tarlov score compared to that in the Tat (vehicle)-treated group at 24, 48 and 72 h after ischemia/reperfusion. At 72 h after ischemia/reperfusion, the number of cresyl violet-positive neurons was significantly increased in the Tat-DJ-1-treated group compared to that in the vehicle-treated group. Lipid peroxidation as judged from the malondialdehyde levels was significantly decreased in the Tat-DJ-1-treated group compared to that in the vehicle-treated group. In contrast, superoxide dismutase and catalase levels were significantly increased in the Tat-DJ-1-treated group compared to that in the vehicle-treated group. This result suggests that DJ-1 protects neurons from ischemic damage in the ventral horn of the spinal cord via its antioxidant effects.  相似文献   
133.
Circling mice manifest profound deafness, head-tossing, and bi-directional circling behavior, which they inherit in autosomal recessive manner. Histologic examination of the inner ear reveals abnormalities of the region around the organ of Corti, spiral ganglion neurons, and outer hair cells. A genetic linkage map was constructed for an intraspecific backcross between cir and C57BL/6J mice. The cir gene was mapped to a region between D9Mit116/D9Mit15 and D9Mit38 on mouse chromosome (Chr) 9. Estimated distances between cir and D9Mit116, and between cir and D9Mit38 were 0.70 +/- 0.40 and 0.23 +/- 0.23 cM, respectively. Order of the markers was defined as follows: centromere - D9Mit182 - D9Mit51/D9Mit79/D9Mit310 - D9Mit212/D184 - D9Mit116/D9Mit15 - cir - D9Mit38 - D9Mit20 - D9Mit243 - D9Mit16 - D9Mit55/D9Mit125 - D9Mit281. On the basis of genetic mapping, we constructed a yeast artificial chromosome (YAC) contig across the cir region. The cir gene is located between the lactotransferrin (ltf) and microtubule-associated protein (map4) genes. The distal portion of mouse Chr 9 encompassing the cir region is homologous with human chromosome 3p21, which contains the Deafness, form B: Autosomal Recessive Deafness (DFNB6) locus. Therefore, the circling mouse is a potential animal model for DFNB6 deafness in humans.  相似文献   
134.
    
Bz‐423 is an inhibitor of the mitochondrial F1F0‐ATPase, with therapeutic properties in murine models of immune diseases. Here, we study the binding of a water‐soluble Bz‐423 analog (5‐(3‐(aminomethyl)phenyl)‐7‐chloro‐ 1‐methyl‐3‐(naphthalen‐2‐ylmethyl)‐1H‐benzo][e][1,4]diazepin‐2(3H)‐one); (1) to its target subunit on the enzyme, the oligomycin sensitivity conferring protein (OSCP), by NMR spectroscopy using chemical shift perturbation and cross‐relaxation experiments. Titration experiments with constructs representing residues 1–120 or 1–145 of the OSCP reveals that (a) 1 binds to a region of the protein, at the minimum, comprising residues M51, L56, K65, V66, K75, K77, and N92, and (b) binding of 1 induces conformational changes in the OSCP. Control experiments employing a variant of 1 in which a key binding element on the small molecule was deleted; it had no perturbational effect on the spectra of the OSCP, which indicates that the observed changes with 1 represent specific binding interactions. Collectively, these data suggest that 1 might inhibit the enzyme through an allosteric mechanism where binding results in conformational changes that perturb the OSCP‐F1 interface resulting in disrupted communication between the peripheral stalk and the F1‐domain of the enzyme. © 2009 Wiley Periodicals, Inc. Biopolymers 29: 85–92, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com  相似文献   
135.
    
This review describes the PARTRAC suite of comprehensive Monte Carlo simulation tools for calculations of track structures of a variety of ionizing radiation qualities and their biological effects. A multi-scale target model characterizes essential structures of the whole genomic DNA within human fibroblasts and lymphocytes in atomic resolution. Calculation methods and essential results are recapitulated regarding the physical, physico-chemical and chemical stage of track structure development of radiation damage induction. Recent model extension towards DNA repair processes extends the time dimension by about 12 orders of magnitude and paves the way for superior predictions of radiation risks.  相似文献   
136.
    
The increasing problem of antibiotic resistance among pathogenic bacteria requires development of new antimicrobial agents. For the purpose of this study, a cDNA encoding hinnavin II‐α‐melanocyte stimulating hormone (hin/MSH) hybrid was chemically synthesized, annealed, and then cloned into transfer vector pBacPAK 9 for expression in Sf21 insect cells. Recombinant hin/MSH (rhin/MSH) hybrid was efficiently produced in baculovirus expression vector system (BEVS) as a hybrid peptide. The antibacterial activity of the rhin/MSH hybrid was compared to that of the recombinant hinnavin II (rhin), using inhibition zone and overlay assay. This new recombinant hybrid peptide may serve as an attractive candidate for powerful novel class of antimicrobial pharmaceuticals.  相似文献   
137.

Background

This study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV) for 2010–2011.

Methodology/Principal Findings

Health care workers (HCW) vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK) or HCW vaccinated in 2010 with the 2010–2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE) was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7%) reported 468 events compared to 328 of the 7645 HCW (4.3%) who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010–2011 seasonal vaccine (1% vs. 0.03%, p<0.001). Paresthesia was reported by 7 HCW (0.1%) after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up.

Conclusion

The 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010–2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ≥1 per 1000 vaccinations but is insufficient to detect rare AE.

Trial Registration

ClinicalTrials.gov NCT01289418, NCT01318876  相似文献   
138.
Above- and belowground biomass and nitrogen (N) and phosphorus (P) distribution within threeQuercus acutissima stands were investigated in central Korea. The average age (year) and diameter at breast height (DBH, cm) were 10.8 and 7.9 for Stand 1, 38.2 and 17.1 for Stand 2, and 44.0 and 20.7 for Stand 3, respectively. Fifteen trees were destructively harvested for dimension analysis of component biomass (stem wood, stem bark, foliage, branches, and roots) plus N and P concentrations. Total biomass (t ha-1) was 88.7 for Stand 1, 154.9 for Stand 2, and 278.1 for Stand 3 while N and P contents in all tree components (kg ha-1) were 483.3 and 52.2, 697.1 and 55.0, and 1113.9 and 83.7. Nitrogen concentrations were highest in the foliage, followed by the stem bark, branches or roots, and stem wood. In contrast, P concentrations were greatest in the roots, then foliage, branches, stem bark, and stem wood. In general, N and P concentrations in these components significantly decreased with tree age and DBH, while N and P contents significantly increased with age and size. These relationships were stronger for size than for age. Our current data could be utilized to estimate N and P budgets for silvicultural practices, including fertilization, thinning, and harvesting.  相似文献   
139.
To characterize the NYJ strain of pseudorabies virus (PRV; Alphaherpesvirus of swine) isolated from the serum of an infected swine in Korea, the nucleotide sequence of three major glycoproteins (gB, gC, and gD) was analyzed. The expression of most potent immunogenic glycoprotein (gD) was also investigated using a Bombyx mori nucleopolyhedrovirus (BmNPV) expression system. The length of the glycoprotein genes corresponding to gB, gC, and gD of the NYJ strain were 2751 bp, 1443 bp, and 1203, respectively, and their identity ranged from 94.2% to 99.8% when compared with other strains. Phylogenetic analyses using these sequences showed that the NYJ strain forms a distinct branch with high bootstrap support. A novel transfer vector (pBmKSK4) was engineered with the polyhedrin promoter of BmNPV and a 6xHis tag to express glycoprotein gD in Bm5 cells and silkworm, B. mori, larvae. The immunogenicity of recombinant gD was demonstrated by its specific detection in both Bm5 cells and silkworm larvae by porcine anti-PRV antibody. The results of this study have implications both for the taxonomy of Korean PRV strains and vaccine development.  相似文献   
140.
Susceptibility of the lepidopteran parasitoid Hyposoter didymator (Thunberg) to seven modern insecticides, azadirachtin, diflubenzuron, halofenozide, methoxyfenozide, pyriproxyfen, tebufenozide, and spinosad, was tested in the laboratory. Pupae were exposed to different doses of each compound by direct topical application. At the field recommended doses, methoxyfenozide and tebufenozide had no effect on H. didymator. Halofenozide had a low effect on both adult emergence and adult survival but the progeny size and parasitism capacity were not affected. Diflubenzuron was moderately toxic to the parasitoid, while azadirachtin, pyriproxyfen and spinosad were very toxic, affecting all its life parameters. In the pyriproxyfen and spinosad treatments, no progeny was obtained. As a second approach of this study, we determined the rate of penetration through the pupal cocoon and absorption in the parasitoid body as pharmacokinetic parameters important for toxicity. Most of the radioactivity was retained in the silken cocoon, indicating a low accumulation in the parasitoid body. Among all compounds tested, diflubenzuron exhibited the highest absorption in the parasitoid body, followed by pyriproxyfen. For halofenozide, methoxyfenozide and tebufenozide, low absorption (<2%) was found. In addition, we tested for the presence of molting hormone receptors in Hyposoter tissues using a monoclonal antibody 9B9. Our data suggest that the use of diflubenzuron azadirachtin, pyriproxyfen, halofenozide, and spinosad in combination with H. didymator in integrated pest management (IPM) programs should be carefully evaluated. Methoxyfenozide and tebufenozide could be considered safe for this parasitoid.  相似文献   
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