The Deuterator: software for the determination of backbone amide deuterium levels from H/D exchange MS data

Background  

The combination of mass spectrometry and solution phase amide hydrogen/deuterium exchange (H/D exchange) experiments is an effective method for characterizing protein dynamics, and protein-protein or protein-ligand interactions. Despite methodological advancements and improvements in instrumentation and automation, data analysis and display remains a tedious process. The factors that contribute to this bottleneck are the large number of data points produced in a typical experiment, each requiring manual curation and validation, and then calculation of the level of backbone amide exchange. Tools have become available that address some of these issues, but lack sufficient integration, functionality, and accessibility required to address the needs of the H/D exchange community. To date there is no software for the analysis of H/D exchange data that comprehensively addresses these issues.     

Host plant volatiles synergize responses of sex pheromone-specific olfactory receptor neurons in male <Emphasis Type="Italic">Helicoverpa zea</Emphasis>

Single-cell electrophysiological recordings were obtained from olfactory receptor neurons in antennal trichoid sensilla of male corn earworm, Helicoverpa zea. Spontaneous activity of the neuron specific for the major component ( Z)-11-hexadecenal, the conspecific female-emitted sex pheromone, was not affected by exposure to host plant volatiles. However, stimulations with binary mixtures of a threshold dosage of the pheromone component and increasing dosages of either linalool or ( Z)-3-hexenol significantly synergized the pheromone-specific neuron's firing rates compared with responses to the major pheromone component alone. Cross-adaptation studies confirmed that the enhanced impulses originated from the pheromone-component-tuned neuron. Because plant volatiles do not stimulate the pheromone-specific neuron when presented alone, the pheromone plus host odor blend would be interpreted as containing more pheromone than it actually does when processed by the pheromone-processing portion of the antennal lobe.     

Differing burden and epidemiology of non-Typhi Salmonella bacteremia in rural and urban Kenya, 2006-2009

Background

The epidemiology of non-Typhi Salmonella (NTS) bacteremia in Africa will likely evolve as potential co-factors, such as HIV, malaria, and urbanization, also change.

Methods

As part of population-based surveillance among 55,000 persons in malaria-endemic, rural and malaria-nonendemic, urban Kenya from 2006–2009, blood cultures were obtained from patients presenting to referral clinics with fever ≥38.0°C or severe acute respiratory infection. Incidence rates were adjusted based on persons with compatible illnesses, but whose blood was not cultured.

Results

NTS accounted for 60/155 (39%) of blood culture isolates in the rural and 7/230 (3%) in the urban sites. The adjusted incidence in the rural site was 568/100,000 person-years, and the urban site was 51/100,000 person-years. In both sites, the incidence was highest in children <5 years old. The NTS-to-typhoid bacteremia ratio in the rural site was 4.6 and in the urban site was 0.05. S. Typhimurium represented >85% of blood NTS isolates in both sites, but only 21% (urban) and 64% (rural) of stool NTS isolates. Overall, 76% of S. Typhimurium blood isolates were multi-drug resistant, most of which had an identical profile in Pulse Field Gel Electrophoresis. In the rural site, the incidence of NTS bacteremia increased during the study period, concomitant with rising malaria prevalence (monthly correlation of malaria positive blood smears and NTS bacteremia cases, Spearman''s correlation, p = 0.018 for children, p = 0.16 adults). In the rural site, 80% of adults with NTS bacteremia were HIV-infected. Six of 7 deaths within 90 days of NTS bacteremia had HIV/AIDS as the primary cause of death assigned on verbal autopsy.

Conclusions

NTS caused the majority of bacteremias in rural Kenya, but typhoid predominated in urban Kenya, which most likely reflects differences in malaria endemicity. Control measures for malaria, as well as HIV, will likely decrease the burden of NTS bacteremia in Africa.     

Biased mutations and microsatellite variation

Mutation bias is one of the forces that may constrain the variation at microsatellite loci. Here, we study the dynamics of population statistics and the genetic distance between two populations under multiple stepwise mutations with linear bias and random drift. Expressions are derived for these statistics as functions of time, as well as at mutation-drift equilibrium. Applying these expressions to published data on humans and chimpanzees, the regression coefficient of mutation bias on allele size was estimated to be at least between - 0.0064 and -0.013. The assumption of mutational bias produces larger estimates of divergence times than are obtained in its absence; in particular, the time of split between African and non-African human populations is estimated to be between 183,000 and 222,000 years, assuming one-step mutations and no selection. With multistep mutations, the divergence time is estimated to be lower.      

Effects of Water Stress and Abscisic Acid on Transpiration Regulation in Wheat

The transpiration response to recurrent light periods was studied'n water-stressed wheat seedlings. Seedlings were stressed by three methods: addition of mannitol to the root medium, root cooling and drving of the roots in air. All three methods induced almost equal effects on transpiration regulation during alternating dark and light intervals. Exogenous abscisic acid supplied to the shoots of excised plants had qualitatively the same effect as water stress. Water stress and ABA increased the time lapse between light-on and the onset of transpiration increase and lowered the amplitude of transpiration increase in light. Weak light introduced before strong light shortened the delay times.     

长爪沙鼠高胆固醇血症模型的建立与辛伐他汀的作用

目的探索长爪沙鼠高胆固醇血症模型建立及辛伐他汀的影响。方法在饲喂长爪沙鼠高脂饲料的同时给予不同浓度辛伐他汀抑制胆固醇生物合成,通过观察肝脏颜色,测量体重、肝重、TC、LDL-C及HDL-C等血脂和肝功能指标判断高脂饲料和辛伐他汀对血脂和肝脏功能的影响。结果动物体重、肝重和肝脏指数没有显著变化。高脂饲料能够促进脂肪在肝脏的沉积,但是对AST和ALT等肝脏功能指标影响不显著;辛伐他汀能够有效抑制TC、LDL-C、HDL-C、TBA和GLU的升高,但对其他指标影响不明显。结论高脂饲料能够快速建立长爪沙鼠高胆固醇血症模型;辛伐他汀能够抑制内源性胆固醇的合成从而有效抑制血浆胆固醇（TC）、LDL-C和HDL-C的升高。结果表明,特殊的反馈调节机制导致长爪沙鼠无法在大量摄入胆固醇时终止内源性胆固醇的合成。长爪沙鼠特殊的反馈调节机制可能是易发高胆固醇血症的一个主要原因。     

Heavy drinking relates to positive valence ratings of alcohol cues

A positive family history of alcohol use disorders (FH) is a robust predictor of personal alcohol abuse and dependence. Exposure to problem-drinking models is one mechanism through which family history influences alcohol-related cognitions and drinking patterns. Similarly, exposure to alcohol advertisements is associated with alcohol involvement and the relationship between affective response to alcohol cues and drinking behavior has not been well established. In addition, the collective contribution that FH, exposure to different types of problem-drinking models (e.g. parents, peers) and personal alcohol use have on appraisal of alcohol-related stimuli has not been evaluated with a large sample. We investigated the independent effects of FH, exposure to problem-drinking models and personal alcohol use on valence ratings of alcohol pictures in a college sample. College students (n = 227) completed measures of personal drinking and substance use, exposure to problem-drinking models, FH and ratings on affective valence of 60 alcohol pictures. Greater exposure to non-familial problem-drinkers predicted greater drinking among college students (beta = 0.17, P < 0.01). However, personal drinking was the only predictor of valence ratings of alcohol pictures (beta = -0.53, P < 0.001). Personal drinking level predicted valence ratings of alcohol cues over and above FH, exposure to problem-drinking models and demographic characteristics. This suggests that positive affective responses to alcohol pictures are more a function of personal experience (i.e. repeated heavy alcohol use) than vicarious learning.     

Fetuin-A ({alpha}2HS-glycoprotein) is a major serum adhesive protein that mediates growth signaling in breast tumor cells

The identity of the cell adhesive factors in fetal bovine serum, commonly used to supplement growth media, remains a mystery due to the plethora of serum proteins. In the present analyses, we showed that fetuin-A, whose function in cellular attachment in tissue culture has been debated for many years, is indeed a major serum cell attachment factor particularly for tumor cells. We are able to report this because of a new purification strategy that has for the first time given us a homogeneous protein band in colloidal Coomassie-stained gels that retains biological activity. The tumor cells adhered to immobilized fetuin-A and not α(2)-macroglobulin, its major contaminant. The interaction of cells with fetuin-A was driven mainly by Ca(2+) ions, and cells growing in regular medium supplemented with fetal bovine serum were just as sensitive to loss of extracellular Ca(2+) ions as cells growing in fetuin-A. Fractionation of human serum revealed that cell attachment was confined to the fractions that had fetuin-A. Interestingly, the tumor cells also took up fetuin-A and secreted it back to the medium using an unknown mechanism that can be observed in live cells. The attachment of tumor cells to fetuin-A was accompanied by phosphatidylinositol 3-kinase/Akt activation that was down-regulated in cells that lack annexin-A6, one of the cell surface receptors for fetuin-A. Taken together, our data show the significance of fetuin-A in tumor cell growth mechanisms in vitro and open new research vistas for this protein.     

Biosynthesis of chlorophyll P-680 of photosystem II in greening leaves of plants adapted to heat shock

In etiolated pea and maize leaves illuminated after incubation at 38 degreesC, a new dark reaction was shown manifested in the bathochromic shift of spectral bands and accompanied by esterification of the product of protochlorophyllide photochemical reduction--Chld 684/676: Chld 684/676 --> Chl 688/680. After completion of the reaction a rapid (20-30 sec) quenching of the fluorescence of the reaction product (Chl 688/680) was observed. The reaction Chld 684/676 --> Chl 688/680 is inhibited under anaerobic conditions and in the presence of cyanide; the reaction accompanied by Chl 688/680 fluorescence quenching is not observed in pea mutants with impaired function of photosystem II reaction centers. The spectral properties of the formed Chl form with the absorption maximum at 680 nm, fluorescence quenching, and simultaneous synthesis of pheophytin suggest that the reaction is connected with the chlorophyll of photosystem II reaction center--P-680.