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41.
Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation, investigations have predominately focused on Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFalpha). However, to date no studies have investigated the expression of these cytokines simultaneously in IVD degeneration or herniation, or determined which may be the predominant cytokine associated with these disease states. Using quantitative real time PCR and immunohistochemistry we investigated gene and protein expression for IL-1beta, TNFalpha and their receptors in non-degenerate, degenerate and herniated human IVDs. IL-1beta gene expression was observed in a greater proportion of IVDs than TNFalpha (79% versus 59%). Degenerate and herniated IVDs displayed higher levels of both cytokines than non-degenerate IVDs, although in degenerate IVDs higher levels of IL-1beta gene expression (1,300 copies/100 ng cDNA) were observed compared to those of TNFalpha (250 copies of TNFalpha/100 ng cDNA). Degenerate IVDs showed ten-fold higher IL-1 receptor gene expression compared to non-degenerate IVDs. In addition, 80% of degenerate IVD cells displayed IL-1 receptor immunopositivity compared to only 30% of cells in non-degenerate IVDs. However, no increase in TNF receptor I gene or protein expression was observed in degenerate or herniated IVDs compared to non-degenerate IVDs. We have demonstrated that although both cytokines are produced by human IVD cells, IL-1beta is expressed at higher levels and in more IVDs, particularly in more degenerate IVDs (grades 4 to 12). Importantly, this study has highlighted an increase in gene and protein production for the IL-1 receptor type I but not the TNF receptor type I in degenerate IVDs. The data thus suggest that although both cytokines may be involved in the pathogenesis of IVD degeneration, IL-1 may have a more significant role than TNFalpha, and thus may be a better target for therapeutic intervention. 相似文献
42.
43.
Abstract
Integration of habitat heterogeneity into spatially realistic metapopulation approaches reveals the potential for key cross-scale
interactions. Broad-scale environmental gradients and land-use practices can create autocorrelation of habitat quality of
suitable patches at intermediate spatial scales. Patch occupancy then depends not only on habitat quality at the patch scale
but also on feedbacks from surrounding neighborhoods of autocorrelated patches. Metapopulation dynamics emerge from how demographic
and dispersal processes interact with relevant habitat heterogeneity. We provide an empirical example from a metapopulation
of round-tailed muskrats (Neofiber
alleni) in which habitat quality of suitable patches was spatially autocorrelated most strongly within 1,000 m, which was within
the expected dispersal range of the species. After controlling for factors typically considered in metapopulation studies—patch
size, local patch quality, patch connectivity—we use a cross-variogram analysis to demonstrate that patch occupancy by muskrats
was correlated with habitat quality across scales ≤1,171 m. We also discuss general consequences of spatial heterogeneity
of habitat quality for metapopulations related to potential cross-scale interactions. We focus on spatially correlated extinctions
and metapopulation persistence, hierarchical scaling of source–sink dynamics, and dispersal decisions by individuals in relation
to information constraints. 相似文献
44.
Lyn Dimond 《BMJ (Clinical research ed.)》1915,2(2865):778-779
45.
Molecular basis for the potency of IL-10-deficient dendritic cells as a highly efficient APC system for activating Th1 response 总被引:2,自引:0,他引:2
46.
Beauregard A Chalamcharla VR Piazza CL Belfort M Coros CJ 《Molecular microbiology》2006,62(3):709-722
Group II introns are mobile genetic elements that invade their cognate intron-minus alleles via an RNA intermediate, in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. In Escherichia coli, retrotransposition of the lactococcal group II intron, Ll.LtrB, occurs preferentially within the Ori and Ter macrodomains of the E. coli chromosome. These macrodomains migrate towards the poles of the cell, where the intron-encoded protein, LtrA, localizes. Here we investigate whether alteration of nucleoid condensation, chromosome partitioning and replication affect retrotransposition frequencies, as well as bipolar localization of the Ll.LtrB intron integration and LtrA distribution in E. coli. We thus examined these properties in the absence of the nucleoid-associated proteins H-NS, StpA and MukB, in variants of partitioning functions including the centromere-like sequence migS and the actin homologue MreB, as well as in the replication mutants DeltaoriC, seqA, tus and topoIV (ts). Although there were some dramatic fluctuations in retrotransposition levels in these hosts, bipolar localization of integration events was maintained. LtrA was consistently found in nucleoid-free regions, with its localization to the cellular poles being largely preserved in these hosts. Together, these results suggest that bipolar localization of group II intron retrotransposition results from the residence of the intron-encoded protein at the poles of the cell. 相似文献
47.
Santos RL Hassan MJ Sikandar S Lee K Ali G Martin PE Wambangco MA Ahmad W Leal SM 《Human genetics》2006,120(1):85-92
From a large collection of families with autosomal recessive non-syndromic hearing impairment (NSHI) from Pakistan, linkage has been established for two unrelated consanguineous families to 19p13.2. This new locus was assigned the name DFNB68. A 10 cM genome scan and additional fine mapping were carried out using microsatellite marker loci. Linkage was established for both families to DFNB68 with maximum multipoint LOD scores of 4.8 and 4.6. The overlap of the homozygous regions between the two families was bounded by D19S586 and D19S584, which limits the locus interval to 1.9 cM and contains 1.4 Mb. The genes CTL2, KEAP1 and CDKN2D were screened but were negative for functional sequence variants.Regie Lyn P. Santos and Muhammad Jawad Hassan contributed equally to this work. 相似文献
48.
Hassan MJ Santos RL Rafiq MA Chahrour MH Pham TL Wajid M Hijab N Wambangco M Lee K Ansar M Yan K Ahmad W Leal SM 《Human genetics》2006,118(5):605-610
Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual
HI account for ~75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried
out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and
D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the
three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers
combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes,
KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants. 相似文献
49.
A parA homolog selectively influences positioning of the large chromosome origin in Vibrio cholerae 下载免费PDF全文
A Vibrio cholerae deletion mutant lacking VS2773, a parA partitioning gene homolog located in a parAB operon on the large chromosome, displays altered positioning of the large chromosome origin. Deletion of a second parA homolog on the large chromosome (VC2061) does not affect its origin positioning. The origin position of the small chromosome is unchanged by either or both of these deletions, suggesting that VC2773 function is specific to the replicon on which it is carried. VC2773 and VC2772 form a parABS system with inverted repeats found near the large chromosome origin. 相似文献
50.
Stawski CY Grigg GC Booth DT Beard LA 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2006,143(2):173-183
We investigated the capacity of two reptiles, an agamid lizard Pogona barbata and a chelid turtle Emydura signata, to compensate for the effects of temperature by making changes in their whole blood respiratory properties. This was accomplished by measuring the P50 (at 10, 20 and 30 degrees C), hematocrit (Hct), haemoglobin concentration ([Hb]) and mean cell haemoglobin concentration (MCHC) in field acclimatised and laboratory acclimated individuals. The acute effect of temperature on P50 in P. barbata, expressed as heat of oxygenation (deltaH), ranged from -16.8+/-1.84 to -28.5+/-2.73 kJ/mole. P50 of field acclimatised P. barbata increased significantly from early spring to summer at the test temperatures of 20 degrees C (43.1+/-1.2 to 48.8+/-2.1 mmHg) and 30 degrees C (54.7+/-1.2 to 65.2+/-2.3 mmHg), but showed no acclimation under laboratory conditions. For E. signata, deltaH ranged from -31.1+/-6.32 to -48.2+/-3.59 kJ/mole. Field acclimatisation and laboratory acclimation of P50 did not occur. However, in E. signata, there was a significant increase in [Hb] and MCHC from early spring to summer in turtles collected from the wild (1.0+/-0.1 to 1.7+/-0.2 mmol/L and 4.0+/-0.3 to 6.7+/-0.7 mmol/L, respectively). 相似文献