微机在牙形刺研究中的应用

该文对微机在牙形刺研究中的应用方法上进行了探索,在大量原始资料和数据的基础上,采用了模糊聚类分析和CAI计算机程序系统的研究,在地层划分,化石组合,沉积环境分析及生油气评价等方面都取得了一定的成果。     

Immunochemical characterization and cellular localization of pepsinogens in cat and dog.

The antigenic relationships and cellular localization of cat and dog pepsinogens were investigated by electrophoretic analysis, immunodiffusion, immunoelectrophoresis, immunoabsorption, and by immunofluorescence, respectively. Rabbit antiserum to human and hog group I (Pg I) and group II pepsinogens (Pg II) had been previously prepared. Electrophoretic analysis revealed at least eight distinct proteases in extracts of gastric and proximal duodenal mucosa, resistant to alkalinization but destroyed by sequential accidification and neutralization. Rabbit antiserum to Pg I (anti-Pg I) and Pg II (anti-Pg II) produced a single precipitin arc against each extract forming a line of nonidentity. Immunoelectrophoresis of extracts produced a single precipitin arc against anti-Pg I or anti-Pg II. The specificity of the antibodies for the group I or group II pepsinogens was confirmed by immunoabsorption. By immunofluorescnece, both Pg I and Pg II were present in mucous neck and chief cells in fundic mucosa, in the pyloric gland cells in antral mucosa, and Brunner's glands in the proximal duodenum. The results indicate that canine and feline pepsinogens are electrophoretically heterogenous, that canine and feline Pg I share antigenic determinants with each other but not with Pg II, that a similar positive relationship exists for Pg II, and that both Pg I and Pg II are localized to the peptic cell mass, consisting of four types of cells.     

Phosphorylation alters the pH-dependent active state equilibrium of rhodopsin by modulating the membrane surface potential.

Phosphorylation reduces the lifetime and activity of activated G protein-coupled receptors, yet paradoxically shifts the metarhodopsin I-II (MI-MII) equilibrium (K(eq)) of light-activated rhodopsin toward MII, the conformation that activates G protein. In this report, we show that phosphorylation increases the apparent pK for MII formation in proportion to phosphorylation stoichiometry. Decreasing ionic strength enhances this effect. Gouy-Chapman theory shows that the change in pK is quantitatively explained by the membrane surface potential, which becomes more negative with increasing phosphorylation stoichiometry and decreasing ionic strength. This lowers the membrane surface pH compared to the bulk pH, increasing K(eq) and the rate of MII formation (k(1)) while decreasing the back rate constant (k(-)(1)) of the MI-MII relaxation. MII formation has been observed to depend on bulk pH with a fractional stoichiometry of 0.6-0.7 H(+)/MII. We find that the apparent fractional H(+) dependence is an artifact of altering the membrane surface charge during a titration, resulting in a fractional change in membrane surface pH compared to bulk pH. Gouy-Chapman calculations of membrane pH at various phosphorylation levels and ionic strengths suggest MII formation behavior consistent with titration of a single H(+) binding site with 1:1 stoichiometry and an intrinsic pK of 6.3 at 0.5 degrees C. We show evidence that suggests this same site has an intrinsic pK of 5.0 prior to light activation and its protonation before activation greatly enhances the rate of MII formation.     

Cis-vaccenic acid and the Framingham risk score predict chronic kidney disease: the multi-ethnic study of atherosclerosis (MESA)

IntroductionData on the associations of fatty acids with chronic kidney disease (CKD) are sparse.Materials and methodsWe performed a cross-sectional study of 2792 men and women from the MESA cohort of African–American, Caucasian, Chinese and Hispanic adults without known cardiovascular disease. Plasma phospholipid fatty acid proportions were associated with estimated glomerular filtration rate (eGFR) and the albumin/creatinine ratio.ResultsCis-vaccenic acid (18:1n?7), adjusted for other fatty acids using multivariate logistic regression (CI: 1.0–1.4), and step-wise logistic regression (CI: 1.02–1.42), was positively associated with reduced eGFR. The Framingham Risk Score, when adjusting for fatty acid proportions and demographic factors, was positively associated with CKD as measured by the eGFR and the albumin/creatinine ratio.Discussion and conclusionsPlasma phospholipid proportions of the 18 carbon monounsaturated cis-vaccenic acid {18:1n?7}) and the Framingham Risk Score are associated with kidney function. The potential role of 18:1n?7 in the development of CKD warrants further investigation.     

Mechanism of ATP quench of phosphodiesterase activation in rod disc membranes

GTP-dependent light activation of cyclic GMP phosphodiesterase in bovine rod disc membranes was quenched by ATP. ATP reduced both initial velocity (V0) and turn off time (toff) of phosphodiesterase activated by a flash that bleached 1.5 X 10(-5) of the rhodopsin present. In the absence of rhodopsin kinase, ATP had no effect on either V0 or toff of reconstituted preparations containing phosphodiesterase and GTP*-binding protein. Addition of partially purified rhodopsin kinase to such reconstitutions again permitted ATP to quench both initial velocity and turn off time. It is thus likely that kinase-mediated phosphorylation of bleached rhodopsin reduces and arrests light-induced phosphodiesterase activation. Thermolysin cleavage of rhodopsin's COOH-terminal dodecapeptide eliminated ATP's effect on toff, but did not diminish its effect on V0. Thus, the effects of ATP and kinase on V0 may be mediated by sites proximal to and effects on toff by sites distal to the thermolysin cleavage point at rhodopsin's COOH-terminal end.     

Prion formation and polyglutamine aggregation are controlled by two classes of genes

Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of prions. De novo appearance of the [PSI ⁺] prion, which is the aggregated form of the Sup35 protein, is dramatically enhanced by transient overexpression of SUP35 in the presence of the prion form of the Rnq1 protein, [PIN ⁺]. When fused to GFP and overexpressed in [ps⁻] [PIN ⁺] cells, Sup35 forms fluorescent rings, and cells with these rings bud off [PSI ⁺] daughters. We investigated the effects of over 400 gene deletions on this de novo induction of [PSI ⁺]. Two classes of gene deletions were identified. Class I deletions (bug1Δ, bem1Δ, arf1Δ, and hog1Δ) reduced the efficiency of [PSI ⁺] induction, but formed rings normally. Class II deletions (las17Δ, vps5Δ, and sac6Δ) inhibited both [PSI⁺] induction and ring formation. Furthermore, class II deletions reduced, while class I deletions enhanced, toxicity associated with the expanded glutamine repeats of the huntingtin protein exon 1 that causes Huntington''s disease. This suggests that prion formation and polyglutamine aggregation involve a multi-phase process that can be inhibited at different steps.     

The story of stolen chaperones

Prions are self-seeding alternate protein conformations. Most yeast prions contain glutamine/asparagine (Q/N)-rich domains that promote the formation of amyloid-like prion aggregates. Chaperones, including Hsp104 and Sis1, are required to continually break these aggregates into smaller “seeds.” Decreasing aggregate size and increasing the number of growing aggregate ends facilitates both aggregate transmission and growth. Our previous work showed that overexpression of 11 proteins with Q/N-rich domains facilitates the de novo aggregation of Sup35 into the [PSI⁺] prion, presumably by a cross-seeding mechanism. We now discuss our recent paper, in which we showed that overexpression of most of these same 11 Q/N-rich proteins, including Pin4C and Cyc8, destabilized pre-existing Q/N rich prions. Overexpression of both Pin4C and Cyc8 caused [PSI⁺] aggregates to enlarge. This is incompatible with a previously proposed “capping” model where the overexpressed Q/N-rich protein poisons, or “caps,” the growing aggregate ends. Rather the data match what is expected of a reduction in prion severing by chaperones. Indeed, while Pin4C overexpression does not alter chaperone levels, Pin4C aggregates sequester chaperones away from the prion aggregates. Cyc8 overexpression cures [PSI⁺] by inducing an increase in Hsp104 levels, as excess Hsp104 binds to [PSI⁺] aggregates in a way that blocks their shearing.     

Determinants of Heterogeneous Blood Feeding Patterns by Aedes aegypti in Iquitos,Peru

Background

Heterogeneous mosquito biting results in different individuals in a population receiving an uneven number of bites. This is a feature of many vector-borne disease systems that, if understood, could guide preventative control efforts toward individuals who are expected to contribute most to pathogen transmission. We aimed to characterize factors determining biting patterns of Aedes aegypti, the principal mosquito vector of dengue virus.

Methodology/Principal Findings

Engorged female Ae. aegypti and human cheek swabs were collected from 19 houses in Iquitos, Peru. We recorded the body size, age, and sex of 275 consenting residents. Movement in and out of the house over a week (time in house) and mosquito abundance were recorded on eight separate occasions in each household over twelve months. We identified the individuals bitten by 96 engorged mosquitoes over this period by amplifying specific human microsatellite markers in mosquito blood meals and human cheek swabs. Using a multinomial model assuming a saturating relationship (power), we found that, relative to other residents of a home, an individual''s likelihood of being bitten in the home was directly proportional to time spent in their home and body surface area (p<0.05). A linear function fit the relationship equally well (ΔAIC<1).

Conclusions/Significance

Our results indicate that larger people and those who spend more time at home are more likely to receive Ae. aegypti bites in their homes than other household residents. These findings are consistent with the idea that measurable characteristics of individuals can inform predictions of the extent to which different people will be bitten. This has implications for an improved understanding of heterogeneity in different people''s contributions to pathogen transmission, and enhanced interventions that include the people and places that contribute most to pathogen amplification and spread.