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131.
Marcos G Godoy Alejandra Aedo Molly JT Kibenge David B Groman Carmencita V Yason Horts Grothusen Angelica Lisperguer Marlene Calbucura Fernando Avendaño Marcelo Imilán Miguel Jarpa Frederick SB Kibenge 《BMC veterinary research》2008,4(1):1-13
Background
Several forms of progressive retinal atrophy (PRA) segregate in more than 100 breeds of dog with each PRA segregating in one or a few breeds. This breed specificity may be accounted for by founder effects and genetic drift, which have reduced the genetic heterogeneity of each breed, thereby facilitating the identification of causal mutations. We report here a new form of PRA segregating in the Border Collie breed. The clinical signs, including the loss of night vision and a progressive loss of day vision, resulting in complete blindness, occur at the age of three to four years and may be detected earlier through systematic ocular fundus examination and electroretinography (ERG). 相似文献132.
133.
Matthew W Strobeck David N Reisman Ranjaka W Gunawardena Bryan L Betz Steven P Angus Karen E Knudsen Timothy F Kowalik Bernard E Weissman Erik S Knudsen 《The Journal of biological chemistry》2002,277(7):4782-4789
The BRG-1 subunit of the SWI-SNF complex is involved in chromatin remodeling and has been implicated in the action of the retinoblastoma tumor suppressor (RB). Given the importance of BRG-1 in RB function, germ line BRG-1 mutations in tumorigenesis may be tantamount to RB inactivation. Therefore, in this study we assessed the behavior of cells harboring discrete BRG-1 alleles for the RB-signaling pathway. Using p16ink4a, an upstream activator of endogenous RB, or a constitutively active RB construct (PSM-RB), we determined that the majority of tumor lines with germ line defects in BRG-1 were sensitive to RB-mediated cell cycle arrest. By contrast, A427 (lung carcinoma) cells were resistant to expression of p16ink4a and PSM-RB. Analysis of the SWI-SNF subunits in the different tumor lines revealed that A427 are deficient for BRG-1 and its homologue, Brm, whereas RB-sensitive cell lines retained Brm expression. Similarly, the RB-resistant SW13 and C33A cell lines were also deficient for both BRG-1/Brm. Reintroduction of either BRG-1 or Brm into A427 or C33A cells restored RB-mediated signaling to cyclin A to cause cell cycle arrest. Consistent with this compensatory role, we observed that Brm could also drive expression of CD44. We also determined that loss of these core SWI-SNF subunits renders SW13 cells resistant to activation of the RB pathway by the chemotherapeutic agent cisplatin, since reintroduction of either BRG-1 or Brm into SW13 cells restored the cisplatin DNA-damage checkpoint. Together, these data demonstrate that Brm can compensate for BRG-1 loss as pertains to RB sensitivity. 相似文献
134.
Study of the Infectivity of Saline-Stored Campylobacter jejuni for Day-Old Chicks 总被引:1,自引:0,他引:1
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The culturability of three Campylobacter jejuni strains and their infectivity for day-old chicks were assessed following storage of the strains in saline. The potential for colonization of chicks was weakened during the storage period and terminated 3 to 4 weeks before the strains became nonculturable. The results from this study suggest that the role of starved and aged but still culturable campylobacters may be diminutive, but even more, that the role of viable but nonculturable stages in campylobacter epidemiology may be negligible. Even high levels of maternally derived anti-campylobacter outer membrane protein serum antibodies in day-old chicks did not protect the chicks from campylobacter colonization. 相似文献
135.
136.
Mitochondrial localization of p53 has been observed in several cell systems, but an understanding of its organelle-based physiological activity remains incomplete. The purpose of the present study was to investigate the mitochondrial DNA genomic response to dominant-negative p53 mutant miniprotein (p53DD) fused to a mitochondrial import signal. Constructs were generated to express mitochondrial targeted enhanced green fluorescent protein (mEGFP) or dominant-negative mutant p53 miniprotein (m53DD) by in-frame fusion to the signal peptide sequence of murine Cox8l. Control cytosolic vectors (cEGFP, c53DD) had the signal sequence placed in antisense orientation. NIH 3T3 cells were transiently transfected with these vectors in various combinations. Mitochondrial 16S ribosomal RNA (16S rRNA) expression and fluorochrome staining with Mitotracker Red CMXRos (DeltaPsim) were decreased in cells expressing m53DD. Both alterations were specific for mitochondrial import competence (e.g., m53DD vs. c53DD) as well as the passenger protein (e.g., m53DD vs. mEGFP). The normal functional state of mitochondria was restored with PK11195, a specific ligand of the mitochondrial peripheral-type benzodiazepine receptor. Negative dominance of m53DD on 16S rRNA expression and CMXRos staining, and rescue of these parameters with PK11195, imply a direct positive effect of p53 on mitochondrial biogenesis and function. 相似文献
137.
Cyanobacteria are only prokaryotes known so far to have a circadian system. It may be based either on two (kaiB and kaiC) or three (kaiA, kaiB and kaiC) circadian genes. The homologs of two circadian proteins, KaiB and KaiC, form four major subfamilies (K1–K4) and also occur
in some other prokaryotes. Using the likelihood-ratio tests, we studied a rate shift at the functional divergence of the proteins
from the different subfamilies. It appears that only two of the subfamilies (K1 and K2) perform circadian functions. We identified
in total 92 sites that have significantly different rates of evolution between the clades K1/K2 and K3/K4; 67 sites (15 in
KaiB and 52 in KaiC) been evolving significantly slower in K1/K2 than the overall average for the entire sequence. Many critical
sites are located in the identified functionally important motifs and regions, e.g. one of the Walker’s motif As, DXXG motif,
and two KaiA-binding domains of KaiC. There are also 36 sites (~5%) with rate shift between K1 and K2. The rate shift at these
sites may be related to the interaction with KaiA. Rate shift analyses have identified residues whose manipulation in the
Kai proteins may lead to better understanding of their functions in the two different types of the cyanobacterial circadian
system. 相似文献
138.
Christopher A. Reed Christopher N. Mayhew A. Kathleen McClendon Erik S. Knudsen 《The Journal of biological chemistry》2010,285(2):1089-1096
The retinoblastoma (RB) tumor suppressor pathway is disrupted at high frequency in hepatocellular carcinoma. However, the mechanisms through which RB modulates physiological responses in the liver remain poorly defined. Despite the well established role of RB in cell cycle control, the deletion of RB had no impact on the kinetics of cell cycle entry or the restoration of quiescence during the course of liver regeneration. Although these findings indicated compensatory effects from the RB-related proteins p107 and p130, even the dual deletion of RB with p107 or p130 failed to deregulate hepatic proliferation. Furthermore, although these findings suggested a modest role for the RB-pathway in the context of proliferative control, RB loss had striking effects on response to the genotoxic hepatocarcinogen diethylnitrosamine. With diethylnitrosamine, RB deletion resulted in inappropriate cell cycle entry that facilitated secondary genetic damage and further uncoupling of DNA replication with mitotic entry. Analysis of the mechanism underlying the differential impact of RB status on liver biology revealed that, while liver regeneration is associated with the conventional induction of cyclin D1 expression, the RB-dependent cell cycle entry, occurring with diethylnitrosamine treatment, was independent of cyclin D1 levels and associated with the specific induction of E2F1. Combined, these studies demonstrate that RB loss has disparate effects on the response to unique tumorigenic stresses, which is reflective of distinct mechanisms of cell cycle entry. 相似文献
139.
A method for the extraction of acyl-CoA esters from tissue, and their subsequent analysis by HPLC is described. The lipids are removed by a two-phase extraction in a chloroform/methanol/water system. The long-chain acyl-CoA esters are extracted using methanol and a high salt concentration (2 M ammonium acetate). Reextraction of the dry residue after evaporation of extraction solvent results in low overall recoveries (20%). By adding 1 mg/ml acyl-CoA-binding protein to the extraction solvent the overall recovery was increased to 55%. The method is easy and fast to perform and is thereby suitable for analysis of a large number of samples. The advantages of the method over previously published methods are discussed. 相似文献
140.