排序方式: 共有168条查询结果,搜索用时 15 毫秒
71.
Hoffman LM Garcha K Karamboulas K Cowan MF Drysdale LM Horton WA Underhill TM 《The Journal of cell biology》2006,174(1):101-113
The bone morphogenetic protein (BMP) and growth and differentiation factor (GDF) signaling pathways have well-established and essential roles within the developing skeleton in coordinating the formation of cartilaginous anlagen. However, the identification of bona fide targets that underlie the action of these signaling molecules in chondrogenesis has remained elusive. We have identified the gene for the retinoic acid (RA) synthesis enzyme Aldh1a2 as a principal target of BMP signaling; prochondrogenic BMPs or GDFs lead to attenuation of Aldh1a2 expression and, consequently, to reduced activation of the retinoid signaling pathway. Consistent with this, antagonism of retinoid signaling phenocopies BMP4 action, whereas RA inhibits the chondrogenic stimulatory activity of BMP4. BMP4 also down-regulates Aldh1a2 expression in organ culture and, consistent with this, Aldh1a2 is actively excluded from the developing cartilage anlagens. Collectively, these findings provide novel insights into BMP action and demonstrate that BMP signaling governs the fate of prechondrogenic mesenchyme, at least in part, through regulation of retinoid signaling. 相似文献
72.
A population level computational model of the basal ganglia that generates parkinsonian local field potential activity 总被引:1,自引:0,他引:1
George L. Tsirogiannis George A. Tagaris Damianos Sakas Konstantina S. Nikita 《Biological cybernetics》2010,102(2):155-176
Recordings from the basal ganglia’s subthalamic nucleus are acquired via microelectrodes immediately prior to the application
of Deep Brain Stimulation (DBS) treatment for Parkinson’s Disease (PD) to assist in the selection of the final point for the
implantation of the DBS electrode. The acquired recordings reveal a persistent characteristic beta band peak in the power
spectral density function of the Local Field Potential (LFP) signals. This peak is considered to lie at the core of the causality–effect
relationships of the parkinsonian pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we constructed
a computational model of the basal ganglia on the population level that generates LFPs to identify the critical pathophysiological
alterations that lead to the expression of the beta band peak. To this end, we used experimental data reporting that the strengths
of the synaptic connections are modified under dopamine depletion. The hypothesis that the altered dopaminergic modulation
may affect both the amplitude and the time course of the postsynaptic potentials is validated by the model. The results suggest
a pivotal role of both of these parameters to the pathophysiology of PD. 相似文献
73.
Background
One of the earliest activation events following stimulation of the T cell receptor (TCR) is the phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs) within the CD3-associated complex by the Src family kinase Lck. There is accumulating evidence that a large pool of Lck is constitutively active in T cells but how the TCR is connected to Lck and to the downstream signaling cascade remains elusive.Methodology/Principal Findings
We have analyzed the phosphorylation state of Lck and Fyn and TCR signaling in human naïve CD4+ T cells and in the transformed T cell line, Hut-78. The latter has been shown to be similar to primary T cells in TCR-inducible phosphorylations and can be highly knocked down by RNA interference. In both T cell types, basal phosphorylation of Lck and Fyn on their activatory tyrosine was observed, although this was much less pronounced in Hut-78 cells. TCR stimulation led to the co-precipitation of Lck with the transmembrane adaptor protein LAT (linker for activation of T cells), Erk-mediated phosphorylation of Lck and no detectable dephosphorylation of Lck inhibitory tyrosine. Strikingly, upon LAT knockdown in Hut-78 cells, we found that LAT promoted TCR-induced phosphorylation of Lck and Fyn activatory tyrosines, TCRζ chain phosphorylation and Zap-70 activation. Notably, LAT regulated these events at low strength of TCR engagement.Conclusions/Significance
Our results indicate for the first time that LAT promotes TCR signal initiation and suggest that this adaptor may contribute to maintain active Lck in proximity of their substrates. 相似文献74.
Golfinopoulos A Kopsahelis N Tsaousi K Koutinas AA Soupioni M 《Bioresource technology》2011,102(5):4204-4209
The present investigation examines the effect of pH, temperature and cell concentration on lactose uptake rate, in relation with kinetics of whey fermentation using kefir and determines the optimum conditions of these parameters. Lactose uptake rate was measured by adding 14C-labelled lactose in whey. The results reveal the role of lactose uptake rate, being the main factor that affects the rate of fermentation, in contrast to the activity of the enzymes involved in lactose bioconversion process. Lactose uptake rate results discussion showed that mainly Ca2+ is responsible for the reduced whey fermentation rate in comparison with fermentations using synthetic media containing lactose. Likewise, the results draw up perspectives on whey fermentation research to improve whey fermentation rate. Those perspectives are research to remove Ca2+ from whey, the use of nano and microtubular biopolymers and promoters such as γ-alumina pellets and volcan foaming rock kissiris in order to accelerate whey fermentation. 相似文献
75.
Romain Roncagalli Guo Fu Nicholas RJ Gascoigne Konstantina Nika Andre Cohnen Stephan M Feller Philip C Simister Kelly C Molder Shaun‐Paul Cordoba Omer Dushek Bernard Malissen Oreste Acuto 《The EMBO journal》2015,34(3):393-409
THEMIS is critical for conventional T‐cell development, but its precise molecular function remains elusive. Here, we show that THEMIS constitutively associates with the phosphatases SHP1 and SHP2. This complex requires the adapter GRB2, which bridges SHP to THEMIS in a Tyr‐phosphorylation‐independent fashion. Rather, SHP1 and THEMIS engage with the N‐SH3 and C‐SH3 domains of GRB2, respectively, a configuration that allows GRB2‐SH2 to recruit the complex onto LAT. Consistent with THEMIS‐mediated recruitment of SHP to the TCR signalosome, THEMIS knock‐down increased TCR‐induced CD3‐ζ phosphorylation, Erk activation and CD69 expression, but not LCK phosphorylation. This generalized TCR signalling increase led to augmented apoptosis, a phenotype mirrored by SHP1 knock‐down. Remarkably, a KI mutation of LCK Ser59, previously suggested to be key in ERK‐mediated resistance towards SHP1 negative feedback, did not affect TCR signalling nor ligand discrimination in vivo. Thus, the THEMIS:SHP complex dampens early TCR signalling by a previously unknown molecular mechanism that favours T‐cell survival. We discuss possible implications of this mechanism in modulating TCR output signals towards conventional T‐cell development and differentiation. 相似文献
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77.
We numerically assess the effects of head properties (anatomy and dielectric parameters) on the performance of a scalp‐implantable antenna for telemetry in the Medical Implant Communications Service band (402.0–405.0 MHz). Safety issues and performance (resonance, radiation) are analyzed for an experimentally validated implantable antenna (volume of 203.6 mm3), considering five head models (3‐ and 5‐layer spherical, 6‐, 10‐, and 13‐tissue anatomical) and seven scenarios (variations ± 20% in the reference permittivity and conductivity values). Simulations are carried out at 403.5 MHz using the finite‐difference time‐domain method. Anatomy of the head model around the implantation site is found to mainly affect antenna performance, whereas overall tissue anatomy and dielectric parameters are less significant. Compared to the reference dielectric parameter scenario within the 3‐layer spherical head, maximum variations of ?19.9%, +3.7%, ?55.1%, and ?39.2% are computed in the maximum allowable net input power imposed by the IEEE Std C95.1‐1999 and Std C95.1‐2005 safety guidelines, return loss, and maximum far‐field gain, respectively. Compliance with the recent IEEE Std C95.1‐2005 is found to be almost insensitive to head properties, in contrast with IEEE Std C95.1‐1999. Taking tissue property uncertainties into account is highlighted as crucial for implantable antenna design and performance assessment. Bioelectromagnetics 34:167–179, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
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79.
Konstantina Fragaki Vincent Procaccio Sylvie Bannwarth Valrie Serre Sean OHearn Prasanth Potluri Gaelle Aug Florence Casagrande Cline Caruba Jean Claude Lambert Vronique Paquis-Flucklinger 《Mitochondrion》2009,9(5):346-352
Mutations within the mitochondrially encoded cytochrome b (MTCYB) gene are heteroplasmic and lead to severe exercise intolerance. We describe an unusual clinical presentation secondary to a novel homoplasmic mutation within MTCYB. The m.15635T > C transition (S297P) was carried by a newborn who presented with a polyvisceral failure. This mutation was responsible for a complex III deficiency. It was homoplasmic in all tissues tested and was undetectable in patient’s mother. Functional analyses, including studies on patient’s cybrid cell lines, demonstrate the pathogenicity of this variant. Our data show that mutations within MTCYB can be responsible for severe phenotype at birth. 相似文献
80.
Carotene production from waste cooking oil by Blakeslea trispora in a bubble column reactor: The role of oxidative stress 下载免费PDF全文
Konstantina Nanou Triantafyllos Roukas Emmanuel Papadakis Parthena Kotzekidou 《Engineering in Life Science》2017,17(7):775-780
The oxidative stress induced by hydroperoxides and reactive oxygen species (ROS) during carotene production from waste cooking oil (WCO) and corn steep liquor (CSL) by the fungus Blakeslea trispora in a bubble column reactor was investigated. The specific activities of the intracellular enzymes superoxide dismutase (SOD) and catalase (CAT) as well as the micromorphology of the fungus were measured in order to study the response of the fungus to oxidative stress. The changes of the morphology of microorganism leaded to pellets formation and documented using a computerized image analysis system. As a consequence of the mild oxidative stress induced by hydroperoxides of WCO and ROS a significant increase in carotene production was obtained. The highest carotene concentration (980.0 mg/l or 51.5 mg/g dry biomass) was achieved in a medium consisted of CSL (80.0 g/L) and WCO (50.0 g/L) at an aeration rate of 5 vvm after 6 days of fermentation. In this case the carotenes produced consisted of β‐carotene (71%), γ‐carotene (26%), and lycopene (3%). The strong oxidative stress in the fungus caused a significant increase of γ‐carotene concentration. Bubble column reactor is a useful fermentation system for carotene production in industrial scale. 相似文献