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61.
Foxp3-mediated suppression of CD95L expression confers resistance to activation-induced cell death in regulatory T cells 总被引:1,自引:0,他引:1
62.
Carrai M Steinke V Vodicka P Pardini B Rahner N Holinski-Feder E Morak M Schackert HK Görgens H Stemmler S Betz B Kloor M Engel C Büttner R Naccarati A Vodickova L Novotny J Stein A Hemminki K Propping P Försti A Canzian F Barale R Campa D 《PloS one》2011,6(6):e20464
Molecular sensing in the lingual mucosa and in the gastro-intestinal tract play a role in the detection of ingested harmful drugs and toxins. Therefore, genetic polymorphisms affecting the capability of initiating these responses may be critical for the subsequent efficiency of avoiding and/or eliminating possible threats to the organism. By using a tagging approach in the region of Taste Receptor 2R38 (TAS2R38) gene, we investigated all the common genetic variation of this gene region in relation to colorectal cancer risk with a case-control study in a German population (709 controls and 602 cases) and in a Czech population (623 controls and 601 cases). We found that there were no significant associations between individual SNPs of the TAS2R38 gene and colorectal cancer in the Czech or in the German population, nor in the joint analysis. However, when we analyzed the diplotypes and the phenotypes we found that the non-taster group had an increased risk of colorectal cancer in comparison to the taster group. This association was borderline significant in the Czech population, (OR = 1.28, 95% CI 0.99–1.67; Pvalue = 0.058) and statistically significant in the German population (OR = 1.36, 95% CI 1.06–1.75; Pvalue = 0.016) and in the joint analysis (OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001). In conclusion, we found a suggestive association between the human bitter tasting phenotype and the risk of CRC in two different populations of Caucasian origin. 相似文献
63.
Deoxyribonucleic Acid Replication in Simian Virus 40-Infected Cells: II. Detection and Characterization of Simian Virus 40 Pseudovirions 总被引:3,自引:14,他引:3 下载免费PDF全文
Purified simian virus 40 (SV40) virions, grown in primary African green monkey kidney cells labeled prior to infection with (3)H-thymidine, contain a variable quantity of (3)H-labeled deoxyribonucleic acid (DNA). This DNA is resistant to deoxyribonuclease, sediments at 250S, and is enclosed in a particle that can be precipitated with SV40-specific antiserum. DNA-DNA hybridization experiments demonstrate that this (3)H-labeled component in purified SV40 virions is cellular DNA. When this (3)H-labeled DNA is released from purified virus with sodium dodecyl sulfate, it has an average sedimentation constant of 14S. Sedimentation through neutral and alkaline sucrose gradients shows that this 14S DNA is composed of a collection of different sizes of DNA molecules that sediment between 11 and 15S. As a result of this size heterogeneity, SV40 virions containing cellular DNA (pseudovirions) have a variable DNA to capsid protein ratio and exhibit a spectrum of buoyant densities in a CsCl equilibrium gradient. Pseudovirions are enriched, relative to true virions, on the lighter density side of infectious SV40 virus banded to equilibrium in a CsCl gradient. Little or no cellular DNA was found in purified SV40 virus preparations grown in BSC-1 or CV-1 cells. 相似文献
64.
The Perceived Temperature (PT) is an equivalent temperature based on a complete heat budget model of the human body. It has
proved its suitability for numerous applications across a wide variety of scales from micro to global and is successfully
used both in daily forecasts and climatological studies. PT is designed for staying outdoors and is defined as the air temperature
of a reference environment in which the thermal perception would be the same as in the actual environment. The calculation
is performed for a reference subject with an internal heat production of 135 W m−2 (who is walking at 4 km h−1 on flat ground). In the reference environment, the mean radiant temperature equals the air temperature and wind velocity
is reduced to a slight draught. The water vapour pressure remains unchanged. Under warm/humid conditions, however, it is implicitly
related to a relative humidity of 50%. Clothing is adapted in order to achieve thermal comfort. If this is impossible, cold
or heat stress will occur, respectively. The assessment of thermal perception by means of PT is based on Fanger’s Predicted
Mean Vote (PMV) together with additional model extensions taking account of stronger deviations from thermal neutrality. This
is performed using a parameterisation based on a two-node model. In the cold, it allows the mean skin temperature to drop
below the comfort value. In the heat, it assesses additionally the enthalpy of sweat-moistened skin and of wet clothes. PT
has the advantages of being self-explanatory due to its deviation from air temperature and being—via PMV—directly linked to
a thermo-physiologically-based scale of thermal perception that is widely used and has stood the test of time. This paper
explains in detail the basic equations of the human heat budget and the coefficients of the parameterisations. 相似文献
65.
66.
A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin 总被引:3,自引:0,他引:3
Orlova VV Choi EY Xie C Chavakis E Bierhaus A Ihanus E Ballantyne CM Gahmberg CG Bianchi ME Nawroth PP Chavakis T 《The EMBO journal》2007,26(4):1129-1139
High-mobility group box 1 (HMGB1) is released extracellularly upon cell necrosis acting as a mediator in tissue injury and inflammation. However, the molecular mechanisms for the proinflammatory effect of HMGB1 are poorly understood. Here, we define a novel function of HMGB1 in promoting Mac-1-dependent neutrophil recruitment. HMGB1 administration induced rapid neutrophil recruitment in vivo. HMGB1-mediated recruitment was prevented in mice deficient in the beta2-integrin Mac-1 but not in those deficient in LFA-1. As observed by bone marrow chimera experiments, Mac-1-dependent neutrophil recruitment induced by HMGB1 required the presence of receptor for advanced glycation end products (RAGE) on neutrophils but not on endothelial cells. In vitro, HMGB1 enhanced the interaction between Mac-1 and RAGE. Consistently, HMGB1 activated Mac-1 as well as Mac-1-mediated adhesive and migratory functions of neutrophils in a RAGE-dependent manner. Moreover, HMGB1-induced activation of nuclear factor-kappaB in neutrophils required both Mac-1 and RAGE. Together, a novel HMGB1-dependent pathway for inflammatory cell recruitment and activation that requires the functional interplay between Mac-1 and RAGE is described here. 相似文献
67.
Vimal A. Patel Daniel J. Lee Lanfei Feng Angelika Antoni Wilfred Lieberthal John H. Schwartz Joyce Rauch David S. Ucker Jerrold S. Levine 《The Journal of biological chemistry》2010,285(3):1829-1840
During apoptosis, cells acquire new activities that enable them to modulate the fate and function of interacting phagocytes, particularly macrophages (mϕ). Although the best known of these activities is anti-inflammatory, apoptotic targets also influence mϕ survival and proliferation by modulating proximal signaling events, such as MAPK modules and Akt. We asked whether modulation of these same signaling events extends to epithelial cells, a minimally phagocytic cell type. We used BU.MPT cells, a mouse kidney epithelial cell line, as our primary model, but we also evaluated several epithelial cell lines of distinct tissue origins. Like mϕ, mouse kidney epithelial cells recognized apoptotic and necrotic targets through distinct non-competing receptors, albeit with lower binding capacity and markedly reduced phagocytosis. Also, modulation of inflammatory activity and MAPK-dependent signaling by apoptotic and necrotic targets was indistinguishable in kidney epithelial cells and mϕ. In contrast, modulation of Akt-dependent signaling differed dramatically between kidney epithelial cells and mϕ. In kidney epithelial cells, modulation of Akt was linked to target cell recognition, independently of phagocytosis, whereas in mϕ, modulation was linked to phagocytosis. Moreover, recognition of apoptotic and necrotic targets by kidney epithelial cells elicited opposite responses; apoptotic targets inhibited whereas necrotic targets stimulated Akt activity. These data confirm that nonprofessional phagocytes recognize and respond to dying cells, albeit in a manner partially distinct from mϕ. By acting as sentinels of environmental change, apoptotic and necrotic targets may permit neighboring viable cells, especially non-migratory epithelial cells, to monitor and adapt to local stresses. 相似文献
68.
Eggert S Paliga K Soba P Evin G Masters CL Weidemann A Beyreuther K 《The Journal of biological chemistry》2004,279(18):18146-18156
Amyloid precursor protein (APP) processing is of major interest in Alzheimer's disease research, since sequential cleavages by beta- and gamma-secretase lead to the formation of the 4-kDa amyloid Abeta protein peptide that accumulates in Alzheimer's disease brain. The processing of APP involves proteolytic conversion by different secretases leading to alpha-, beta-, gamma-, delta-, and epsilon-cleavages. Since modulation of these cleavages represents a rational therapeutic approach to control amyloid formation, its interference with the processing of the members of the APP gene family is of considerable importance. By using C-terminally tagged constructs of APLP-1 and APLP-2 and the untagged proteins, we have characterized their proteolytic C-terminal fragments produced in stably transfected SH-SY5Y cells. Pharmacological manipulation with specific protease inhibitors revealed that both homologues are processed by alpha- and gamma-secretase-like cleavages, and that their intracellular domains can be released by cleavage at epsilon-sites. APLP-2 processing appears to be the most elaborate and to involve alternative cleavage sites. We show that APLP-1 is the only member of the APP gene family for which processing can be influenced by N-glycosylation. Additionally, we were able to detect p3-like fragments of APLP-1 and p3-like and Abeta-like fragments of APLP-2 in the media of stably transfected SH-SY5Y cells. 相似文献
69.
70.
Boris Wilmes Angelika Hartung Michael Lalk Manuel Liebeke Thomas Schweder Peter Neubauer 《Microbial cell factories》2010,9(1):72