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91.
Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling 下载免费PDF全文
Edwige Roy Zoltan Neufeld Luca Cerone Ho Yi Wong Samantha Hodgson Jean Livet Kiarash Khosrotehrani 《The EMBO journal》2016,35(24):2658-2670
Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones. Two modes of clonal progression could be observed in the adult murine dorsal skin. Clones attached to hair follicles showed rapid increase in size during the growth phase of the hair cycle. On the other hand, clones distant from hair follicles were slow cycling, but could be mobilized by a proliferative stimulus. Reinforced by mathematical modelling, these data support a model where progenitor cycling characteristics are differentially regulated in areas surrounding or away from growing hair follicles. Thus, while IFE progenitors follow a non‐hierarchical mode of development, spatiotemporal control by their environment can change their potentialities, with far‐reaching implications for epidermal homeostasis, wound repair and cancer development. 相似文献
92.
Fausto Machicao Andreas Peter Jürgen Machann Ingmar K?nigsrainer Anja B?hm Stefan Zoltan Lutz Martin Heni Andreas Fritsche Fritz Schick Alfred K?nigsrainer Norbert Stefan Hans-Ulrich H?ring Harald Staiger 《PloS one》2016,11(1)
Circadian rhythms govern vital functions. Their disruption provokes metabolic imbalance favouring obesity and type-2 diabetes. The aim of the study was to assess the role of clock genes in human prediabetes. To this end, genotype-phenotype associations of 121 common single nucleotide polymorphisms (SNPs) tagging ARNTL, ARNTL2, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIMELESS were assessed in a study population of 1,715 non-diabetic individuals metabolically phenotyped by 5-point oral glucose tolerance tests. In subgroups, hyperinsulinaemic-euglycaemic clamps, intravenous glucose tolerance tests, and magnetic resonance imaging/spectroscopy were performed. None of the tested SNPs was associated with body fat content, insulin sensitivity, or insulin secretion. Four CRY2 SNPs were associated with fasting glycaemia, as reported earlier. Importantly, carriers of these SNPs’ minor alleles revealed elevated fasting glycaemia and, concomitantly, reduced liver fat content. In human liver tissue samples, CRY2 mRNA expression was directly associated with hepatic triglyceride content. Our data may point to CRY2 as a novel switch in hepatic fuel metabolism promoting triglyceride storage and, concomitantly, limiting glucose production. The anti-steatotic effects of the glucose-raising CRY2 alleles may explain why these alleles do not increase type-2 diabetes risk. 相似文献
93.
Norihisa Ishii Constantin N. Baxevanis Zoltan A. Nagy Jan Klein 《Immunogenetics》1981,14(3-4):283-292
T lymphocytes recognize the synthetic polypeptides GA and GLT and the natural antigen LDHB and are thereby stimulated to proliferate in vitro. Simultaneously with the antigen, T cells recognize class II MHC molecules of the antigen-presenting cell and the T-cell proliferation can therefore be inhibited by the addition of monoclonal antibodies specific for either A (AA
) or E (EF
) molecules. Antibody blocking of in vitro responses thus provides an opportunity to test the rules governing the selection of class II molecules (A versus E) in the recognition of different antigens. To determine these rules we tested T cells for some 40 strains (classical inbred strains and B10.W lines) carrying H-2 haplotypes derived from wild mice) for their proliferative response to GA, GLT, and LDHB. Strains that responded were then tested in the antibody-blocking assay to determine the class II context of the response. The response to GA occurred always in the context of the A molecule; no single instance was found of the response being channelled through the E molecule. Of the 19 different A molecules (A allomorphs) that could be tested, nine (47 percent) were able to provide the context for GA recognition (and hence conferred responsiveness), while the rest failed to do so (conferred nonresponsiveness). Of the 17 informative cases tested for the response to LDHB, 14 channelled the response through the A molecule, while, in the remaining cases, the cells failed to respond altogether. And again, there was no case where the response was channelled through the E molecule. However, in two instances (of 14) the E molecule provided the context for the stimulation of suppressor T cells, which then suppressed the response of helper T cells occurring in the context of the A molecule. Of the 19 cases tested for the response to GLT, eight channelled the response through the E molecule and two through the A molecule. The two cases of an E A switch were those in which the strains failed to express cell-surface E molecules as a result of a mutation in one of the E-encoding loci. These data indicate a remarkable but puzzling consistency in the channelling of the response to a given antigen via either A or E molecules. This consistency may be a hint that there is a link between the specificity of antigen (nonself) and MHC (self) recognition by T lymphocytes.Abbreviations used in this paper APC
antigen-presenting cell
- GA
poly (Glu40Ala60)
- GLT
poly (Glu51Lys34Tyr15)
- Ir
immune response
- LDHB
lactate dehydrogenase 134
- MHC
major histocompatibility complex
- TH
T helper (cell)
- TS
T suppressor (cell) 相似文献
94.
Mario Sanchez Borges Yoshihiro Kumagai Ko Okumura Nakami Hirayama Zoltan Ovary Tomio Tada 《Immunogenetics》1981,13(6):499-507
Two alloantisera against hybridoma-derived IgE detected allotypic determinants expressed on the murine s chain. An antiserum raised in BALB/c mice against monoclonal IgE of C57BL/6 origin reacted exclusively with IgE of strains having Igh-1b (IgG2a) allotype. The second antiserum, C57BL/6 anti-BALB/c monoclonal IgE, reacted with IgE of strains having Igh-1a, Igh-1d, Igh-1e and Igh-1j allotypes. The genetic studies of (BALB/c x C57BL/6)F1 and backcross F2 animals indicated that the locus controlling the IgE allotype is linked to the Igh-1 locus. This was further confirmed by the possession of respective IgE allotypes by Igh-C congenic mice, BALB/c and BAB-14, C3H.SW/Hz and CWB/Hz. Thus, the allotype detected on the chain is controlled by the seventh murine immunoglobulin allotype locus, and should be designated as the Igh-7 allotype.Abbreviations used in this paper PCA
passive cutaneous anaphylaxis
- RID
radioimmunodiffusion
- i.p.
intraperitoneally
- EA
egg albumin
- Igh-C
immunoglobulin heavy chain constant region locus
- DNP
2,4-dinitrophenyl
- PBS
phosphate-buffered saline
- NMS
normal mouse serum
- KLH
keyhole limpet hemocyanin
Visiting investigator supported by the Scientific and Humanistic Development Council from the Central University of Venezuela, currently at the following address: Consejo de Desarrollo Cientifico y Universidad Central de Venezuela, Av. Principal Urb. La Floresta Ota., Silenia Caracas, Venezuela. 相似文献
95.
96.
Nabil A. Mansour James J. Valdes Adil E. Shamoo Zoltan Annau 《Journal of biochemical and molecular toxicology》1987,2(1):25-42
Purified Torpedo nobiliana electric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)-stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3-H]-phencyclidine ([3-H]-PCP) binding to the channel sites, acting as a weak agonist. The activation of [3-H]-PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb-activated [3-H]-PCP binding with Ki values of 10, 20, and 1,600 μM, respectively. The inhibition was mixed competitivenoncompetitive in nature. The characteristic response of CRPVF to carb-stimulated [22-Na] influx was inhibited by the three carbamates, with IC-50 values of 6,50, and 1,000 μM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb-stimulated [22-Na] influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125-I]-α- bungarotoxin ([125-I]-α-BGT) with the following decreasing order of potency: Neo < Physo < Eco < Pyrido. Calcium has a direct modulatory role on the time-course inhibition of [125-I]-α-BGT binding by these drugs. While we observed a high potency of Neo and Physo in inhibiting [125-I]-α-BGT binding, it was undetectable for the carbamate insecticide 2-methyl-2-(methylthio)propionaldehyde-O-(methylcarbamoyl)oxime (aldicarb). These data suggest that the potent anticholinesterase carbamate agents interact differently with the AChR and its ionic channel. Their interactions with the nicotinic AChR channel system can be described as (a) weakly agonist, (b) directly acting on the open conformation of the channel, and (c) blocking the AChR-binding sites. 相似文献
97.
98.
Laurence Jones Jacqueline Hollinshead George W.J. Fleet Amber L. Thompson David J. Watkin Zoltan A. Gal Sarah F. Jenkinson Atsushi Kato Robert J. Nash 《Phytochemistry letters》2010,3(3):133-135
The Australian leguminous tree Castanospermum australe contains the anti-viral glucose analogue indolizidine alkaloid castanospermine. As the result of a search for new bioactive carbohydrate-like compounds we now report the isolation of the novel polyhydroxylated pyrrolizidine alkaloid, 1-epialexine, from the leaves and stems of C. australe. 1-Epialexine is a weak inhibitor of β-mannosidase from Cellullomonas fimi. 相似文献
99.
ABA Increases the Desiccation Tolerance of Photosynthesis in the Afromontane Understorey Moss Atrichum androgynum 总被引:1,自引:0,他引:1
Mayaba Nosisa; Beckett Richard P.; Csintalan Zsolt; Tuba Zoltan 《Annals of botany》2001,88(6):1093-1100
The effect of pretreatment with abscisic acid (ABA) on the physiologyof the moss Atrichum androgynum during a desiccationrehydrationcycle was examined. During rehydration following desiccationfor 16 h, net CO2fixation recovered much more slowly than photosystemII (PSII) activity, conditions conducive to the formation ofreactive oxygen species (ROS) in the photosynthetic apparatus.Pretreatment with ABA increased the rate of recovery of photosynthesisand PSII activity, and also doubled non-photochemical quenching(NPQ). Increased NPQ activity will reduce ROS formation, andmay explain in part how ABA hardens the moss to desiccation.In ABA-pretreated, but not untreated mosses, desiccation significantlyincreased the concentration of soluble sugars. Sugar accumulationmay promote vitrification of the cytoplasm and protect membranesduring desiccation. Starch concentrations in freshly collectedA. androgynum were only approx. 40 mg g-1dry mass; they roseslightly during desiccation but were only slightly affectedby ABA pretreatment. ABA did not reduce chlorophyll breakdownduring desiccation. Copyright 2001 Annals of Botany Company Moss, desiccation, abscisic acid, photosynthesis, chlorophyll fluorescence 相似文献
100.