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101.
B?rbel Maus Camille Jung Jestinah M. Mahachie John Jean-Pierre Hugot Emmanuelle Génin Kristel Van Steen 《PloS one》2013,8(10)
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn’s disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn’s disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. 相似文献
102.
Glutamate is the main excitatory amino acid, but its presence in the extracellular milieu has deleterious consequences. It
may induce excitotoxicity and also compete with cystine for the use of the cystine–glutamate exchanger, blocking glutathione
neosynthesis and inducing an oxidative stress-induced cell death. Both mechanisms are critical in the brain where up to 20%
of total body oxygen consumption occurs. In normal conditions, the astrocytes ensure that extracellular concentration of glutamate
is kept in the micromolar range, thanks to their coexpression of high-affinity glutamate transporters (EAATs) and glutamine
synthetase (GS). Their protective function is nevertheless sensitive to situations such as oxidative stress or inflammatory
processes. On the other hand, macrophages and microglia do not express EAATs and GS in physiological conditions and are the
principal effector cells of brain inflammation. Since the late 1990s, a number of studies have now shown that both microglia
and macrophages display inducible EAAT and GS expression, but the precise significance of this still remains poorly understood.
Brain macrophages and microglia are sister cells but yet display differences. Both are highly sensitive to their microenvironment
and can perform a variety of functions that may oppose each other. However, in the very particular environment of the healthy
brain, they are maintained in a repressed state. The aim of this review is to present the current state of knowledge on brain
macrophages and microglial cells activation, in order to help clarify their role in the regulation of glutamate under pathological
conditions as well as its outcome. 相似文献
103.
Arginine, agmatine, putrescine and spermidine were found in the apical parts and leaves of chayote ( Sechium edule Swartz ) at various stages of development. The concentration of agmatine, the immediate decarboxylation product of L-arginine, increased considerably in young leaves at the first emergence of floral buds. Young leaves always had a relatively higher content of agmatine than older ones. There was a decrease in the concentration of agmatine from the apical part to the basal leaves. Agmatine was the predominant amine in young leaves at every stage of development (50–90% of the whole amine pool). It was also predominant in mature leaves when the floral buds appeared (70% of the total amine content). An accumulation of agmatine could not be found in other Cucurbitaceae species. 相似文献
104.
Proteolytic degradation of ribosomal proteins occurs during the preparation of subunits of the cytoplasmic ribosomes of the protozoa Tetrahymena thermophila and the isolated subunits are inactive. Addition of 5 mM iodoacetamide to cell suspensions before extraction inhibits proteolytic activity and permits isolation of active subunits. The protein complements of these subunits have been characterized in two different two-dimensional electrophoretic systems, and their molecular weights have been determined. 相似文献
105.
106.
We investigated the mechanisms implicated in beta-cell mass reduction observed during late fetal and early postnatal malnutrition in the rat. Beta-cell regeneration, including proliferation and neogenesis, was studied after neonatal beta-cell destruction by streptozotocin (STZ). STZ was injected at birth and maternal food restriction was continued until weaning. Beta-cell mass, proliferation, and islet number were quantified by morphometrical measurements on pancreatic sections in STZ-injected normal (C-STZ) and malnourished (R-STZ) rats, with noninjected C and R rats as controls. At day 4, only 20% of the beta cell-mass remained in C-STZ rats. It regenerated to 50% that of noninjected controls, mainly through active neogenesis, as shown by the entire recovery of islet number/cm(2), and also through moderately increased beta-cell proliferation. In contrast, beta-cell mass from R-STZ animals poorly regenerated, despite a dramatic increase of beta-cell proliferation, because islet number/cm(2) recovered insufficiently. In conclusion, perinatal malnutrition impairs neogenesis and the capacity of beta-cell regeneration by neogenesis but preserves beta-cell proliferation, which remains the elective choice to increase beta-cell mass. These results provide an explanation for the impaired capacity of malnourished animals to adapt their beta-cell mass during aging or pregnancy, which aggravate glucose tolerance. 相似文献
107.
Anna Nilsson Thomas E. Fehniger Lena Gustavsson Malin Andersson Kerstin Kenne Gy?rgy Marko-Varga Per E. Andrén 《PloS one》2010,5(7)
Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention. 相似文献
108.
109.
Neurosecretory granules from the rat and bovine neurohypophysis were isolated and some of their biochemical and biophysical properties studied. Neurosecretory granules (NSG) from rat neurohypophysis were labeled, in vivo, with [35S]cysteine and isolated on isoosmotic gradients. Whereas 1 day after labeling most of the radioactivity was found in the lower part of the gradient, 35 days later the isotope was also located in the lighter NSG-containing fraction. Different analytical procedures showed that the lighter fraction, both in bovine and rat NSG, contain more subpopulations of neurophysin-like material than the heavier fraction. The first material to be released during stimulation of secretion, in vivo or in vitro, is mobilized from the heavy NSG. Isolation of rat NSG, at different times during and after dehydration of the animals, reveals that the newly synthesized material is found in the heavy NSG-containing fraction. Furthermore, the results indicate that the newly synthesized NSG are more resistant to lysis than the lighter granules. The results are discussed in relation to the maturation and degradation processes of the granule content and to the functional state of the NSG. 相似文献
110.
Rats were trained to run spontaneously, without stress, in running wheels. The running activity increased gradually and could reach a plateau of 7 km/night after 3–4 weeks. During the first hour of running in the dark phase the squeak threshold increased significantly and remained high in the morning. The degree of increased threshold was correlated to the amount of running activity. The squeak threshold declined during the following 6 hours of inactivity. A rapid decrease in threshold occurred after naloxone (1–2 mg/kg i.p.). It is suggested that long-lasting muscle exercise (e.g. jogging), acupuncture, and low frequency electrical stimulation of afferent nerve fibres produce discharges in muscle afferents which influence central endorphin mechanics giving analgetic effects. 相似文献