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41.
Moffat K 《Nature methods》2012,9(3):242-243
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42.
The study aimed to explore the suicidal process, suicidal communication and psychosocial situation of young suicide attempters in a rural community in Hanoi, Vietnam. Semi-structured interviews were conducted, in a community setting, with 19 suicide attempters aged 15-24 who had been consecutively hospitalized in an intensive care unit. In 12 of 19 cases, the first pressing, distinct and constant suicidal thoughts appeared less than one day before the suicide attempt in question. However, distress and mild, fleeting suicidal thoughts had been present up to six months before the suicide attempt in 16 cases. Five respondents had a suicide plan one to three days before attempting suicide. Altogether, 13 engaged in some form of suicidal communication before their attempt. This communication was, however, difficult for outsiders to interpret. Twelve of the respondents were victims of regular physical abuse and 16 had suffered psychological violence for at least one year before attempting suicide. Eighteen of the respondents used pesticides or raticides in their suicide attempts. None sought advice or consultation in the community despite long-standing psychosocial problems. The strategy of reducing the availability of suicide means (e.g., pesticides or raticides) in Asian countries should be complemented with a long-term suicide-preventive strategy that targets school dropouts and domestic violence, and promotes coping abilities and communication about psychological and social problems as well as recognition of signs of distress and suicidal communication.  相似文献   
43.
Ayers RA  Moffat K 《Biochemistry》2008,47(46):12078-12086
FixL from Bradyrhizobium japonicum is a PAS sensor protein in which two PAS domains covalently linked to a histidine kinase domain are responsible for regulating nitrogen fixation in an oxygen-dependent manner. The more C-terminal PAS domain, denoted bjFixLH, contains a heme cofactor that binds diatomic molecules such as carbon monoxide and oxygen and regulates the activity of the FixL histidine kinase as part of a two-component signaling system. We present the structures of ferric, deoxy, and carbon monoxide-bound bjFixLH in a new space group ( P1) and at resolutions (1.5-1.8 A) higher than the resolutions of those previously obtained. Interestingly, bjFixLH can form two different dimers (in P1 and R32 crystal forms) in the same crystallization solution, where the monomers in one dimer are rotated approximately 175 degrees relative to the second. This suggests that PAS monomers are plastic and that two quite distinct quaternary structures are closely similar in free energy. We use screw rotation analysis to carry out a quantitative pairwise comparison of PAS quaternary structures, which identifies five different relative orientations adopted by isolated PAS monomers. We conclude that PAS monomer arrangement is context-dependent and could differ depending on whether the PAS domains are isolated or are part of a full-length protein. Structurally homologous residues comprise a conserved dimer interface. Using network analysis, we find that the architecture of the PAS dimer interface is continuous rather than modular; the network of residues comprising the interface is strongly connected. A continuous dimer interface is consistent with the low dimer-monomer dissociation equilibrium constant. Finally, we quantitate quaternary structural changes induced by carbon monoxide binding to a bjFixLH dimer, in which monomers rotate by up to approximately 2 degrees relative to each other. We relate these changes to those in other dimeric PAS domains and discuss the role of quaternary structural changes in the signaling mechanisms of PAS sensor proteins.  相似文献   
44.
(连载第十七卷第三期 )6.2.4胰蛋白酶(Trypsin) :扩散激发的 pH跳跃测定有序的催化溶剂结构Singer等人(1993)的研究表明通过仔细选择一个特异的底物有可能改变一个多步反应的动力学轨迹 ;pH跳跃能提供一个有效的 ,依赖于扩散的方法在整个晶体范围内触发一个慢催化事件。在这个例子中 ,丝氨酸蛋白酶胰蛋白酶在亲核反应残基Ser195处被 p-胍基苯甲酸(GB)酰化。这个底物很容易形成一个酰基化酶中间物 ,但进行水解和再生游离酶却很慢。GB结合的胰蛋白酶单晶在 pH5.5下装在流槽中 ,在5秒钟内 ,…  相似文献   
45.
46.
J G Moffat  K M Timms  C N Trotman  W P Tate 《Biochimie》1991,73(7-8):1113-1120
There are two major domains of interaction between the Escherichia coli release factors (RF-1 and RF-2) and each subunit of the ribosome. RF-2 has a binding domain on the shoulder and lower head region of the small subunit at the small lobe distant from the decoding site. This is in close proximity to one of the domains on the large subunit which includes the body dimer of L7/L12 and L11. The other domains of interaction, at the decoding site on the small subunit, and at the peptidyltransferase centre of the large subunit of the ribosome, are some distance from the first two, although the evidence for direct contact with the ribosome is less comprehensive. The release factors may therefore have two distinct structural domains, and in support of this concept RF-1 and RF-2 can both be cleaved into two fragments by papain. Region-specific antibodies, and antibodies against defined peptide within the RF sequences have given an indication that a significant part of an interacting RF molecule is in close proximity to the ribosome surface, confirming an observation by immunoelectron microscopy which suggested that the RF penetrates deeply into the cleft between the two subunits. A region of highly conserved primary sequence between the two release factors from E coli is also conserved in those from B subtilis suggesting it forms an important structural or functional domain. Antibodies against peptides from the N-terminal end of this region strongly inhibit binding of the RF to the ribosome.  相似文献   
47.
The structure of horse methemoglobin reconstituted with deuteroheme, in which the heme vinyl substituents are replaced by hydrogens, has been compared with that of native horse methemoglobin by X-ray difference Fourier techniques. The tertiary structures of the two molecules are almost completely identical, with the exception of small perturbations in the globin which occur in direct response to the missing vinyls. These perturbations are, however, highly localized and do not propagate beyond the immediate vicinity of the hemes. Contrary to expectation, complete removal of these heme vinyls results in much less drastic structural changes than does replacement by ethyl substituents, as in methemoglobin reconstituted with mesoheme.  相似文献   
48.
The energy surface resulting from the protonation of the peptide unit, OCNH, has been calculated non-empirically using the LCAO MO SCF (Gaussian function) method. Providing that rotation of the NH2+ group is permitted, N-protonation is favoured. However a nearly equal energy minimum was obtained for O-protonation, suggesting that when rotation is not permitted, or when two hydrogens are originally present, O-protonation is favoured.  相似文献   
49.
A new dip-inoculum method for detecting bacteriuria which utilizes dehydrated media pads and a nitrite pad attached to a small plastic strip was evaluated in hospitalized patients. Discrepant interpretations were made by independent observers in 9.3% of the specimens with > 10(5) colonies per ml. The media pads failed to support growth of yeast and gave variable results with Staphylococcus epidermidis and non-group D streptococci. False-negative culture results commonly occurred if the patients were receiving antibiotics. The nitrite test occasionally remained positive for brief periods after the elimination of bacteriuria by antibiotics. Conditions and drugs (especially phenazopyridine) which discolor urine interfered with reading both the culture and nitrite tests. Although not suitable for hospital use, or for monitoring therapy, the test strip is probably as reliable as the calibrated loop-streak plate culture for office screening.  相似文献   
50.
There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs.  相似文献   
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