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排序方式: 共有65条查询结果,搜索用时 15 毫秒
1.
Jeff A Johnson Heather RL Lerner Pamela C Rasmussen David P Mindell 《BMC evolutionary biology》2006,6(1):65-12
Background
Populations of the Oriental White-backed Vulture (Gyps bengalensis) have declined by over 95% within the past decade. This decline is largely due to incidental consumption of the non-steroidal anti-inflammatory veterinary pharmaceutical diclofenac, commonly used to treat domestic livestock. The conservation status of other Gyps vultures in southern Asia is also of immediate concern, given the lack of knowledge regarding status of their populations and the continuing existence of taxonomic uncertainties. In this study, we assess phylogenetic relationships for all recognized species and the majority of subspecies within the genus Gyps. The continuing veterinary use of diclofenac is an unknown but potential risk to related species with similar feeding habits to Gyps bengalensis. Therefore, an accurate assessment of the phylogenetic relationships among Gyps vultures should aid in their conservation by clarifying taxonomic uncertainties, and enabling inference of their respective relatedness to susceptible G. bengalensis. 相似文献2.
3.
Adrianna Z. Herskovits Joseph J. Locascio Elaine R. Peskind Ge Li Bradley T. Hyman 《PloS one》2013,8(7)
Amyloid beta (aβ) protein assembles into larger protein aggregates during the pathogenesis of Alzheimer’s disease (AD) and there is increasing evidence that soluble aβ oligomers are a critical pathologic species. Diagnostic evaluations rely on the measurement of increased tau and decreased aβ42 in the cerebrospinal fluid (CSF) from AD patients and evidence for oligomeric aβ in patient CSF is conflicting. In this study, we have adapted a monoclonal single antibody sandwich ELISA assay to a Luminex platform and found that this assay can detect oligomerized aβ42 and sAPPα fragments. We evaluated oligomeric aβ reactivity in 20 patients with AD relative to 19 age matched controls and compared these values with a commercially available Alzbio3 kit that detects tau, phosphorylated tau and aβ42 on the same diagnostic platform. We found that CSF samples of patients with AD had elevated aβ oligomers compared to control subjects (p < 0.05) and the ratio of aβ oligomers to aβ42 was also significantly elevated (p < 0.0001). Further research to develop high sensitivity analytical platforms and rigorous methods of developing stable assay standards will be needed before the analysis of oligomeric aβ becomes a routine diagnostic assay for the evaluation of late onset AD patients. 相似文献
4.
VLJ Whitehall TD Dumenil DM McKeone CE Bond ML Bettington RL Buttenshaw L Bowdler GW Montgomery LF Wockner BA Leggett 《Epigenetics》2014,9(11):1454-1460
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features. 相似文献
5.
6.
Ge Li Elaine R. Peskind Steven P. Millard Peter Chi Izabela Sokal Chang-En Yu Lynn M. Bekris Murray A. Raskind Douglas R. Galasko Thomas J. Montine 《PloS one》2009,4(5)
Background
Brain-derived neurotrophic factor (BDNF) is an activity-dependent secreted protein that is critical to organization of neuronal networks and synaptic plasticity, especially in the hippocampus. We tested hypothesis that reduced CSF BDNF is associated with age-related cognitive decline.Methodology/Principal Findings, and Conclusions/Significance
CSF concentration of BDNF, Aβ42 and total tau were measured in 128 cognitively normal adults (Normals), 21 patients with Alzheimer''s disease (AD), and nine patients with Mild Cognitive Impairment. Apolipoprotein E and BDNF SNP rs6265 genotype were determined. Neuropsychological tests were performed at baseline for all subjects and at follow-up visits in 50 Normals. CSF BDNF level was lower in AD patients compared to age-matched Normals (p = 0.02). CSF BDNF concentration decreased with age among Normals and was higher in women than men (both p<0.001). After adjusting for age, gender, education, CSF Aβ42 and total tau, and APOE and BDNF genotypes, lower CSF BDNF concentration was associated poorer immediate and delayed recall at baseline (both p<0.05) and in follow up of approximately 3 years duration (both p<0.01).Conclusions/Significance
Reduced CSF BDNF was associated with age-related cognitive decline, suggesting a potential mechanism that may contribute in part to cognitive decline in older individuals. 相似文献7.
Perrin RJ Craig-Schapiro R Malone JP Shah AR Gilmore P Davis AE Roe CM Peskind ER Li G Galasko DR Clark CM Quinn JF Kaye JA Morris JC Holtzman DM Townsend RR Fagan AM 《PloS one》2011,6(1):e16032
Background
Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the ‘preclinical’ stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.Methods and Findings
CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85–0.94 95% confidence interval [CI]) and 0.88 (0.81–0.94 CI), respectively.Conclusions
Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions. 相似文献8.
Zhang H Loriaux P Eng J Campbell D Keller A Moss P Bonneau R Zhang N Zhou Y Wollscheid B Cooke K Yi EC Lee H Peskind ER Zhang J Smith RD Aebersold R 《Genome biology》2006,7(8):R73-12
There has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N-linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep http://www.unipep.org--a database of human N-linked glycosites--as a resource for biomarker discovery. 相似文献
9.
alpha 1-Proteinase inhibitor (alpha 1-PI), a member of the serine
proteinase inhibitor superfamily, has a primary role in controlling
neutrophil elastase activity within the mammalian circulation. Several
studies have indicated that the reactive center region of alpha 1-PI, the
amino acid sequence of which is critical to recognition of and binding to
target proteinases, is highly divergent within and among species. This
appears to be a consequence of accelerated rates of evolution that may have
been driven by positive Darwinian selection. In order to examine this and
other features of alpha 1-PI evolution in more detail, we have isolated and
sequenced cDNAs representing alpha 1- PI mRNAs of the mouse species Mus
saxicola and Mus minutoides and have compared these with a number of other
mammalian alpha 1-PI mRNAs. Relative to other mammalian mRNAs, the extent
of nonsynonymous substitution is generally high throughout the alpha 1-PI
mRNA molecule, indicating greater overall rates of amino acid substitution.
Within and among mouse species, the 5'-half of the mRNA, but not the
3'-half, has been homogenized by concerted evolution. Finally, the reactive
center is under diversifying or positive Darwinian selection in murid
rodents (rats, mice) and guinea pigs yet is under purifying selection in
primates and artiodactyls. The significance of these findings to alpha 1-PI
function and the possible selective forces driving evolution of serpins in
general are discussed.
相似文献
10.
Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae 总被引:10,自引:2,他引:8
Arginine decarboxylase (ADC) is an important enzyme in the production of
putrescine and polyamines in plants. It is encoded by a single or low-copy
nuclear gene that lacks introns in sequences studied to date. The rate of
Adc amino acid sequence evolution is similar to that of ndhF for the
angiosperm family studied. Highly conserved regions provide several target
sites for PCR priming and sequencing and aid in nucleotide and amino acid
sequence alignment across a range of taxonomic levels, while a variable
region provides an increased number of potentially informative characters
relative to ndhF for the taxa surveyed. The utility of the Adc gene in
plant molecular systematic studies is demonstrated by analysis of its
partial nucleotide sequences obtained from 13 representatives of
Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order
Capparales) and 1 from the related order Malvales. Two copies of the Adc
gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied
to data except the basal genus Aethionema. The resulting Adc gene tree
provides robust phylogenetic data regarding relationships within the
complex mustard family, as well as independent support for proposed tribal
realignments based on other molecular data sets such as those from
chloroplast DNA.
相似文献