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1.
Plasma lipidome is now increasingly recognized as a potentially important marker of chronic diseases, but the exact extent of its contribution to the interindividual phenotypic variability in family studies is unknown. Here, we used the rich data from the ongoing San Antonio Family Heart Study (SAFHS) and developed a novel statistical approach to quantify the independent and additive value of the plasma lipidome in explaining metabolic syndrome (MS) variability in Mexican American families recruited in the SAFHS. Our analytical approach included two preprocessing steps: principal components analysis of the high-resolution plasma lipidomics data and construction of a subject-subject lipidomic similarity matrix. We then used the Sequential Oligogenic Linkage Analysis Routines software to model the complex family relationships, lipidomic similarities, and other important covariates in a variance components framework. Our results suggested that even after accounting for the shared genetic influences, indicators of lipemic status (total serum cholesterol, TGs, and HDL cholesterol), and obesity, the plasma lipidome independently explained 22% of variability in the homeostatic model of assessment-insulin resistance trait and 16% to 22% variability in glucose, insulin, and waist circumference. Our results demonstrate that plasma lipidomic studies can additively contribute to an understanding of the interindividual variability in MS.  相似文献   
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In bacteria, membrane transporters of the cation diffusion facilitator (CDF) family participate in Zn2 +, Fe2 +, Mn2 +, Co2 + and Ni2 + homeostasis. The functional role during infection processes for several members has been shown to be linked to the specificity of transport. Sinorhizobium meliloti has two homologous CDF genes with unknown transport specificity. Here we evaluate the role played by the CDF SMc02724 (SmYiiP). The deletion mutant strain of SmYiiP (ΔsmyiiP) showed reduced in vitro growth fitness only in the presence of Mn2 +. Incubation of ΔsmyiiP and WT cells with sub-lethal Mn2 + concentrations resulted in a 2-fold increase of the metal only in the mutant strain. Normal levels of resistance to Mn2 + were attained by complementation with the gene SMc02724 under regulation of its endogenous promoter. In vitro, liposomes with incorporated heterologously expressed pure protein accumulated several transition metals. However, only the transport rate of Mn2 + was increased by imposing a transmembrane H+ gradient. Nodulation assays in alfalfa plants showed that the strain ΔsmyiiP induced a lower number of nodules than in plants infected with the WT strain. Our results indicate that Mn2 + homeostasis in S. meliloti is required for full infection capacity, or nodule function, and that the specificity of transport in vivo of SmYiiP is narrowed down to Mn2 + by a mechanism involving the proton motive force.  相似文献   
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A new genetic polymorphism of an unidentified plasma protein (PLP1) in pigs was described by using a method of two-dimensional gel electrophoresis and protein staining. Two codominant alleles, with frequencies of 0.83 and 0.17, were found in the Swedish Yorkshire breed. The PLP1 marker was typed in a three-generation pedigree and tested for linkage against a set of 128 markers. The PLP1 locus showed significant LOD score values with three different microsatellite markers (S0092, DAGK and S005), previously assigned to chromosome 5.  相似文献   
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The metatolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13±0.07 mg/L (range 0.06–0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28±0.22 mg/L (range 0.06–0.87 mg/L) (P<0.01, Student'st-test with correction for unequal variances). Using the mean of the control group +2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.  相似文献   
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A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay.  相似文献   
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There is a diverse range of microbiological challenges facing the food, healthcare and clinical sectors. The increasing and pervasive resistance to broad‐spectrum antibiotics and health‐related concerns with many biocidal agents drives research for novel and complementary antimicrobial approaches. Biofilms display increased mechanical and antimicrobial stability and are the subject of extensive research. Cold plasmas (CP) have rapidly evolved as a technology for microbial decontamination, wound healing and cancer treatment, owing to the chemical and bio‐active radicals generated known collectively as reactive oxygen and nitrogen species. This review outlines the basics of CP technology and discusses the interactions with a range of microbiological targets. Advances in mechanistic insights are presented and applications to food and clinical issues are discussed. The possibility of tailoring CP to control specific microbiological challenges is apparent. This review focuses on microbiological issues in relation to food‐ and healthcare‐associated human infections, the role of CP in their elimination and the current status of plasma mechanisms of action.  相似文献   
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Background

Hydrogen peroxide (H2O2) is an important signaling compound that has recently been identified as a new substrate for several members of the aquaporin superfamily in various organisms. Evidence is emerging about the physiological significance of aquaporin-facilitated H2O2 diffusion.

Scope of review

This review summarizes current knowledge about aquaporin-facilitated H2O2 diffusion across cellular membranes. It focuses on physicochemical and experimental evidence demonstrating the involvement of aquaporins in the transport of this redox signaling compound and discusses the regulation and structural prerequisites of these channels to transmit this signal. It also provides perspectives about the potential importance of aquaporin-facilitated H2O2 diffusion processes and places this knowledge in the context of the current understanding of transmembrane redox signaling processes.

Major conclusions

Specific aquaporin isoforms facilitate the passive diffusion of H2O2 across biological membranes and control H2O2 membrane permeability and signaling in living organisms.

General significance

Redox signaling is a very important process regulating the physiology of cells and organisms in a similar way to the well-characterized hormonal and calcium signaling pathways. Efficient transmembrane diffusion of H2O2, a key molecule in the redox signaling network, requires aquaporins and makes these channels important players in this signaling process. Channel-mediated membrane transport allows the fine adjustment of H2O2 levels in the cytoplasm, intracellular organelles, the apoplast, and the extracellular space, which are essential for it to function as a signal molecule. This article is part of a Special Issue entitled Aquaporins.  相似文献   
10.
The endoplasmic reticulum is the main intracellular Ca2+ store for Ca2+ release during cell signaling. There are different strategies to avoid ER Ca2+ depletion. Release channels utilize first Ca2+-bound to proteins and this minimizes the reduction of the free luminal [Ca2+]. However, if release channels stay open after exhaustion of Ca2+-bound to proteins, then the reduction of the free luminal ER [Ca2+] (via STIM proteins) activates Ca2+ entry at the plasma membrane to restore the ER Ca2+ load, which will work provided that SERCA pump is active. Nevertheless, there are several noxious conditions that result in decreased activity of the SERCA pump such as oxidative stress, inflammatory cytokines, and saturated fatty acids, among others. These conditions result in a deficient restoration of the ER [Ca2+] and lead to the ER stress response that should facilitate recovery of the ER. However, if the stressful condition persists then ER stress ends up triggering cell death and the ensuing degenerative process leads to diverse pathologies; particularly insulin resistance, diabetes and several of the complications associated with diabetes. This scenario suggests that limiting ER stress should decrease the incidence of diabetes and the mobility and mortality associated with this illness.  相似文献   
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