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101.
Background
Combining data from different ethnic populations in a study can increase efficacy of methods designed to identify expression quantitative trait loci (eQTL) compared to analyzing each population independently. In such studies, however, the genetic diversity of minor allele frequencies among populations has rarely been taken into account. Due to the fact that allele frequency diversity and population-level expression differences are present in populations, a consensus regarding the optimal statistical approach for analysis of eQTL in data combining different populations remains inconclusive. 相似文献102.
103.
Li D Parks SB Kushner JD Nauman D Burgess D Ludwigsen S Partain J Nixon RR Allen CN Irwin RP Jakobs PM Litt M Hershberger RE 《American journal of human genetics》2006,79(6):1030-1039
Two common disorders of the elderly are heart failure and Alzheimer disease (AD). Heart failure usually results from dilated cardiomyopathy (DCM). DCM of unknown cause in families has recently been shown to result from genetic disease, highlighting newly discovered disease mechanisms. AD is the most frequent neurodegenerative disease of older Americans. Familial AD is caused most commonly by presenilin 1 (PSEN1) or presenilin 2 (PSEN2) mutations, a discovery that has greatly advanced the field. The presenilins are also expressed in the heart and are critical to cardiac development. We hypothesized that mutations in presenilins may also be associated with DCM and that their discovery could provide new insight into the pathogenesis of DCM and heart failure. A total of 315 index patients with DCM were evaluated for sequence variation in PSEN1 and PSEN2. Families positive for mutations underwent additional clinical, genetic, and functional studies. A novel PSEN1 missense mutation (Asp333Gly) was identified in one family, and a single PSEN2 missense mutation (Ser130Leu) was found in two other families. Both mutations segregated with DCM and heart failure. The PSEN1 mutation was associated with complete penetrance and progressive disease that resulted in the necessity of cardiac transplantation or in death. The PSEN2 mutation showed partial penetrance, milder disease, and a more favorable prognosis. Calcium signaling was altered in cultured skin fibroblasts from PSEN1 and PSEN2 mutation carriers. These data indicate that PSEN1 and PSEN2 mutations are associated with DCM and heart failure and implicate novel mechanisms of myocardial disease. 相似文献
104.
Capture of wild, juvenile herring Clupea pallasii from Puget Sound (Washington, USA) and confinement in laboratory tanks resulted in outbreaks of viral hemorrhagic septicemia (VHS), viral erythrocytic necrosis (VEN) and ichthyophoniasis; however, the timing and progression of the 3 diseases differed. The VHS epidemic occurred first, characterized by an initially low infection prevalence that increased quickly with confinement time, peaking at 93 to 98% after confinement for 6 d, then decreasing to negligible levels after 20 d. The VHS outbreak was followed by a VEN epidemic that, within 12 d of confinement, progressed from undetectable levels to 100% infection prevalence with >90% of erythrocytes demonstrating inclusions. The VEN epidemic persisted for 54 d, after which the study was terminated, and was characterized by severe blood dyscrasias including reduction of mean hematocrit from 42 to 6% and replacement of mature erythrocytes with circulating erythroblasts and ghost cells. All fish with ichthyophoniasis at capture died within the first 3 wk of confinement, probably as a result of the multiple stressors associated with capture, transport, confinement, and progression of concomitant viral diseases. The results illustrate the differences in disease ecology and possible synergistic effects of pathogens affecting marine fish and highlight the difficulty in ascribing a single causation to outbreaks of disease among populations of wild fishes. 相似文献
105.
C Nageswara Raju S Sailaja S Pavan Kumari SJ Dhoble V Ramesh Kumar MV Ramanaiah B Sudhakar Reddy 《Luminescence》2013,28(2):162-168
This article reports on the optical properties of 0.5% mol of Sm3+, Dy3+ ion‐doped B2O3‐TeO2‐Li2O‐AlF3 (LiAlFBT) glasses. The glass samples were characterized by optical absorption and emission spectra. Judd‐Ofelt theory was applied to analyze the optical absorption spectra and calculate the intensity parameters and radiative properties of the emission transitions. The emission spectra of Sm3+ and Dy3+:LiAlFBT glasses showed a bright reddish‐orange emission at 598 nm (4G5/2 → 6H7/2) and an intense yellow emission at 574 nm (4F9/2 → 6H13/2), respectively. Full width at half maximum (FWHM), stimulated emission cross section, gain bandwidth and optical gain values were also calculated to extend the applications of the Sm3+ and Dy3+:LiAlFBT glasses. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
106.
Lopez JV; Culver M; Stephens JC; Johnson WE; O'Brien SJ 《Molecular biology and evolution》1997,14(3):277-286
Differential rates of nucleotide substitution among different gene segments
and between distinct evolutionary lineages is well documented among
mitochondrial genes and is likely a consequence of locus-specific selective
constraints that delimit mutational divergence over evolutionary time. We
compared sequence variation of 18 homologous loci (15 coding genes and 3
parts of the control region) among 10 mammalian mitochondrial DNA genomes
which allowed us to describe different mitochondrial evolutionary patterns
and to produce an estimation of the relative order of gene divergence. The
relative rates of divergence of mitochondrial DNA genes in the family
Felidae were estimated by comparing their divergence from homologous
counterpart genes included in nuclear mitochondrial DNA (Numt, pronounced
"new might"), a genomic fossil that represents an ancient transfer of 7.9
kb of mitochondrial DNA to the nuclear genome of an ancestral species of
the domestic cat (Felis catus). Phylogenetic analyses of mitochondrial
(mtDNA) sequences with multiple outgroup species were conducted to date the
ancestral node common to the Numt and the cytoplasmic (Cymt) mtDNA genes
and to calibrate the rate of sequence divergence of mitochondrial genes
relative to nuclear homologous counterparts. By setting the fastest
substitution rate as strictly mutational, an empirical "selective
retardation index" is computed to quantify the sum of all constraints,
selective and otherwise, that limit sequence divergence of mitochondrial
gene sequences over time.
相似文献
107.
Sigma factor-anti-sigma factor interaction in alginate synthesis: inhibition of AlgT by MucA. 总被引:13,自引:8,他引:5
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Z D Xie C D Hershberger S Shankar R W Ye A M Chakrabarty 《Journal of bacteriology》1996,178(16):4990-4996
108.
The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry 总被引:1,自引:0,他引:1
Wilson LJ Morris TW Wu Q Renick PJ Parker CN Davis MC McKeever HD Hershberger PM Switzer AG Shrum G Sunder S Jones DR Soper SS Dobson RL Burt T Morand KL Stella M 《Bioorganic & medicinal chemistry letters》2001,11(9):1149-1152
An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway. 相似文献
109.
Multiunit or single unit activity recorded simultaneously from frontal cortex (FC) and locus coeruleus (LC) under ketamine anesthesia revealed that both regions show slow oscillatory activity, together or separately. If, however, both regions are engaged in this oscillatory activity, there is a systematic relationship between their phases with peak LC firing always following FC firing by 200–400 ms. This was confirmed by cross-correlational analyses, which indicated that the two structures temporarily form a resonant system. The FC-LC resonant state is, however, loose enough to remain open to other intrinsic or extrinsic influences, keeping the measured frequencies of oscillations at each site slightly different, as demonstrated by a delailed analysis of the autocorrelograms. An injection of lidocaine at the frontal cortex site, while sharply reducing the prefrontal activity to essentially zero, leads to an increase of the LC activity and to a modification of the shape of the LC autocorrelogram, but does not change appreciably the phase relationship between the activity in the two structures during the diminishing activity in FC. 相似文献