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排序方式: 共有650条查询结果,搜索用时 234 毫秒
71.
Parimala R. Vajjhala Ruth E. Mirams Justine M. Hill 《The Journal of biological chemistry》2012,287(50):41732-41743
A key process underlying an innate immune response to pathogens or cellular stress is activation of members of the NOD-like receptor family, such as NLRP3, to assemble caspase-1-activating inflammasome complexes. Activated caspase-1 processes proinflammatory cytokines into active forms that mediate inflammation. Activation of the NLRP3 inflammasome is also associated with common diseases including cardiovascular disease, diabetes, chronic kidney disease, and Alzheimer disease. However, the molecular details of NLRP3 inflammasome assembly are not established. The adaptor protein ASC plays a key role in inflammasome assembly. It is composed of an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain, which are protein interaction domains of the death fold superfamily. ASC interacts with NLRP3 via a homotypic PYD interaction and recruits procaspase-1 via a homotypic caspase recruitment domain interaction. Here we demonstrate that ASC PYD contains two distinct binding sites important for self-association and interaction with NLRP3 and the modulatory protein POP1. Modeling of the homodimeric ASC PYD complex formed via an asymmetric interaction using both sites resembles a type I interaction found in other death fold domain complexes. This interaction mode also permits assembly of ASC PYDs into filaments. Furthermore, a type I binding mode is likely conserved in interactions with NLRP3 and POP1, because residues critical for interaction of ASC PYD are conserved in these PYDs. We also demonstrate that ASC PYD can simultaneously self-associate and interact with NLRP3, rationalizing the model whereby ASC self-association upon recruitment to NLRP3 promotes clustering and activation of procaspase-1. 相似文献
72.
McClain CR Gullett T Jackson-Ricketts J Unmack PJ 《Evolution; international journal of organic evolution》2012,66(7):2204-2215
Variation in chemical energy, that is food availability, is posited to cause variation in body size. However, examinations of the relationship are rare and primarily limited to amniotes and zooplankton. Moreover, the relationship between body size and chemical energy may be impacted by phylogenetic history, clade-specific ecology, and heterogeneity of chemical energy in space and time. Considerable work remains to both document patterns in body size over gradients in food availability and understanding the processes potentially generating them. Here, we examine the functional relationship between body size and chemical energy availability over a broad assortment of marine mollusks varying in habitat and mobility. We demonstrate that chemical energy availability is likely driving body size patterns across habitats. We find that lower food availability decreases size-based niche availability by setting hard constraints on maximum size and potentially on minimum size depending on clade-specific ecology. Conversely, higher food availability promotes greater niche availability and potentially promotes evolutionary innovation with regard to size. We posit based on these findings and previous work that increases in chemical energy are important to the diversification of Metazoans through size-mediated niche processes. 相似文献
73.
Gaofeng Dong Kylie Gross Fangfang Qiao Justine Ferguson Eduardo A. Callegari Khosrow Rezvani Dong Zhang Christian J. Gloeckner Marius Ueffing Hongmin Wang 《Journal of neurochemistry》2012,123(3):437-446
Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats encoding for polyglutamine (polyQ) in the huntingtin (Htt) gene. Despite considerable effort, the mechanisms underlying the toxicity of the mutated Htt protein remains largely uncertain. To identify novel therapeutic targets, we recently employed the approach of tandem affinity purification and discovered that calretinin (Cr), a member of the EF‐hand family of calcium‐binding proteins, is preferentially associated with mHtt, although it also interacts with wild‐type Htt. These observations were supported by coimmunoprecipitation and by colocalization of Cr with mHtt in neuronal cultures. Over‐ expression of Cr reduced mHtt‐caused cytotoxicity in both non‐neuronal and neuronal cell models of HD, whereas knockdown of Cr expression in the cells enhanced mHtt‐caused neuronal cell death. In addition, over‐expression of Cr was also associated with reduction of intracellular free calcium and activation of Akt. These results suggest that Cr may be a potential therapeutic target for treatment of HD. 相似文献
74.
Vincourt JB Etienne S Grossin L Cottet J Bantsimba-Malanda C Netter P Mainard D Libante V Gillet P Magdalou J 《Matrix biology》2012,31(5):290-298
The extracellular matrix (ECM) has long been viewed primarily as an organized network of solid-phase ligands for integrin receptors. During degenerative processes, such as osteoarthritis, the ECM undergoes deterioration, resulting in its remodeling and in the release of some of its components. Matrilin-3 (MATN3) is an almost cartilage specific, pericellular protein acting in the assembly of the ECM of chondrocytes. In the past, MATN3 was found required for cartilage homeostasis, but also involved in osteoarthritis-related pro-catabolic functions. Here, to better understand the pathological and physiological functions of MATN3, its concentration as a circulating protein in articular fluids of human osteoarthritic patients was determined and its functions as a recombinant protein produced in human cells were investigated with particular emphasis on the physical state under which it is presented to chondrocytes. MATN3 down-regulated cartilage extracellular matrix (ECM) synthesis and up-regulated catabolism when administered as a soluble protein. When artificially immobilized, however, MATN3 induced chondrocyte adhesion via a α5β1 integrin-dependent mechanism, AKT activation and favored survival and ECM synthesis. Furthermore, MATN3 bound directly to isolated α5β1 integrin in vitro. TGFβ1 stimulation of chondrocytes allowed integration of exogenous MATN3 into their ECM and ECM-integrated MATN3 induced AKT phosphorylation and improved ECM synthesis and accumulation. In conclusion, the integration of MATN3 to the pericellular matrix of chondrocytes critically determines the direction toward which MATN3 regulates cartilage metabolism. These data explain how MATN3 plays either beneficial or detrimental functions in cartilage and highlight the important role played by the physical state of ECM molecules. 相似文献
75.
Malkusch S Endesfelder U Mondry J Gelléri M Verveer PJ Heilemann M 《Histochemistry and cell biology》2012,137(1):1-10
Colocalization of differently labeled biomolecules is a valuable tool in fluorescence microscopy and can provide information
on biomolecular interactions. With the advent of super-resolution microscopy, colocalization analysis is getting closer to
molecular resolution, bridging the gap to other technologies such as fluorescence resonance energy transfer. Among these novel
microscopic techniques, single-molecule localization-based super-resolution methods offer the advantage of providing single-molecule
coordinates that, rather than intensity information, can be used for colocalization analysis. This requires adapting the existing
mathematical algorithms for localization microscopy data. Here, we introduce an algorithm for coordinate-based colocalization
analysis which is suited for single-molecule super-resolution data. In addition, we present an experimental configuration
for simultaneous dual-color imaging together with a robust approach to correct for optical aberrations with an accuracy of
a few nanometers. We demonstrate the potential of our approach for cellular structures and for two proteins binding actin
filaments. 相似文献
76.
ABSTRACT: BACKGROUND: Due to the limitations of face-to-face communication to teach families how to manage, control and prevent malaria, national and local malaria programmes try to reach people through the radio. However, information regarding the timing of radio messages for the target audiences is lacking. METHODS: Within a large-scale trial (Clinicaltrials.gov: NCT00565071), data regarding the time at which people listen to the radio was collected from 1,628 consenting outpatients (and caregivers for minors) attending six rural government primary level health care centres in Bushenyi and Iganga districts of Uganda from February to July 2011. RESULTS: The majority of households, 1,099 (67.5%) owned a radio. The majority, 1,221 (86.3%), participants had heard about malaria from the radio. Some participants started listening to the radio at about 06.00 East African local time (EAT). The peak hours at which people listen to the radio are 12.00-14.00 and 18.00-23.00 local time. The median time of listening to the radio by men is 20.00 (inter-quartile range (IQR): 18.30-21.00) and women 19.30 (IQR: 13.00-20.30). CONCLUSION: Planners of malaria radio interventions need to broadcast their messages within the two peak EAT of 12.00-14.00 and 18.00-23.00. 相似文献
77.
JM Barker CE Cooper PC Withers AP Cruz-Neto 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2012,163(3-4):336-342
We examine here the thermal physiology of the ash-grey mouse, as there is a paucity of data to explain how Australian rodents meet thermoregulatory demands. Most ash-grey mice remained normothermic over a range of ambient temperatures (10°C to 30°C), although they became hyperthermic at high ambient temperatures. One individual entered torpor at ambient temperatures of 20°C and 25°C, with minimal body temperatures of 24.5°C and 28.4°C respectively, before spontaneously arousing. This is the first evidence of torpor use by an Australian murine rodent. Our data suggest that although ash-grey mice have the physiological ability to use torpor, it is used rarely, presumably due to other behavioural and physiological adaptations. Their higher-than-expected basal metabolic rate (1.56±0.25mLO(2)g(-1)h(-1)) indicates that ash-grey mice do not have a frugal approach to energy expenditure. Other standard physiological variables were typical of a generalised rodent. A readily-available omnivorous diet, nocturnal activity, semi-fossorial habit and social behaviour presumably allow a high energy lifestyle. A reluctance to use torpor, despite an apparent physiological ability to do so, supports the idea that the use of torpor reflects a net balance between the costs and benefits of a heterothermic thermoregulatory strategy. 相似文献
78.
DM Greif M Kumar JK Lighthouse J Hum A An L Ding K Red-Horse FH Espinoza L Olson S Offermanns MA Krasnow 《Developmental cell》2012,23(3):482-493
Some of the most serious diseases involve altered size and structure of the arterial wall. Elucidating how arterial walls are built could aid understanding of these diseases, but little is known about how concentric layers of muscle cells and the outer adventitial layer are assembled and patterned around endothelial tubes. Using histochemical, clonal, and genetic analysis in mice, here we show that the pulmonary artery wall is constructed radially, from the inside out, by two separate but coordinated processes. One is sequential induction of successive cell layers from surrounding mesenchyme. The other is controlled invasion of outer layers by inner layer cells through developmentally regulated cell reorientation and radial migration. We propose that a radial signal gradient controls these processes and provide?evidence that PDGF-B and at least one other signal contribute. Modulation of such radial signaling pathways may underlie vessel-specific differences and pathological changes in arterial wall size and structure. VIDEO ABSTRACT: 相似文献
79.
Justine JL Beveridge I Boxshall GA Bray RA Miller TL Moravec FE Trilles JP Whittington ID 《Aquatic biosystems》2012,8(1):1-29
ABSTRACT: BACKGROUND: Coral reefs are areas of maximum biodiversity, but the parasites of coral reef fishes, and especially their species richness, are not well known. Over an 8-year period, parasites were collected from 24 species of Lutjanidae, Nemipteridae and Caesionidae off New Caledonia, South Pacific. RESULTS: Host-parasite and parasite-host lists are provided, with a total of 207 host-parasite combinations and 58 parasite species identified at the species level, with 27 new host records. Results are presented for isopods, copepods, monogeneans, digeneans, cestodes and nematodes. When results are restricted to well-sampled reef fish species (sample size[THIN SPACE]>[THIN SPACE]30), the number of host-parasite combinations is 20[EN DASH]25 per fish species, and the number of parasites identified at the species level is 9[EN DASH]13 per fish species. Lutjanids include reef-associated fish and deeper sea fish from the outer slopes of the coral reef: fish from both milieus were compared. Surprisingly, parasite biodiversity was higher in deeper sea fish than in reef fish (host-parasite combinations: 12.50 vs 10.13, number of species per fish 3.75 vs 3.00); however, we identified four biases which diminish the validity of this comparison. Finally, these results and previously published results allow us to propose a generalization of parasite biodiversity for four major families of reef-associated fishes (Lutjanidae, Nemipteridae, Serranidae and Lethrinidae): well-sampled fish have a mean of 20 host-parasite combinations per fish species, and the number of parasites identified at the species level is 10 per fish species. CONCLUSIONS: Since all precautions have been taken to minimize taxon numbers, it is safe to affirm than the number of fish parasites is at least ten times the number of fish species in coral reefs, for species of similar size or larger than the species in the four families studied; this is a major improvement to our estimate of biodiversity in coral reefs. Our results suggest that extinction of a coral reef fish species would eventually result in the coextinction of at least ten species of parasites. 相似文献
80.