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By incorporating annotation information into the analysis of next-generation sequencing DNA methylation data, we provide an improvement in performance over current testing procedures. Methylation analysis using genome information (MAGI) is applicable for both unreplicated and replicated data, and provides an effective analysis for studies with low sequencing depth. When compared with current tests, the annotation-informed tests provide an increase in statistical power and offer a significance-based interpretation of differential methylation. 相似文献
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Mitochondrial Sirtuins and Molecular Mechanisms of Aging 总被引:1,自引:0,他引:1
Robert A.H. van de Ven Daniel Santos Marcia C. Haigis 《Trends in molecular medicine》2017,23(4):320-331
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A highly conserved nuclear gene for low-level phylogenetics: elongation factor-1 alpha recovers morphology-based tree for heliothine moths 总被引:6,自引:2,他引:6
Cho S; Mitchell A; Regier JC; Mitter C; Poole RW; Friedlander TP; Zhao S 《Molecular biology and evolution》1995,12(4):650-656
Molecular systematists need increased access to nuclear genes. Highly
conserved, low copy number protein-encoding nuclear genes have attractive
features for phylogenetic inference but have heretofore been applied mostly
to very ancient divergences. By virtue of their synonymous substitutions,
such genes should contain a wealth of information about lower-level
taxonomic relationships as well, with the advantage that amino acid
conservatism makes both alignment and primer definition straightforward. We
tested this postulate for the elongation factor-1 alpha (EF-1 alpha) gene
in the noctuid moth subfamily Heliothinae, which has probably diversified
since the middle Tertiary. We sequenced 1,240 bp in 18 taxa representing
heliothine groupings strongly supported by previous morphological and
allozyme studies. The single most parsimonious gene tree and the
neighbor-joining tree for all nucleotides show almost complete concordance
with the morphological tree. Homoplasy and pairwise divergence levels are
low, transition/transversion ratios are high, and phylogenetic information
is spread evenly across gene regions. The EF-1 alpha gene and presumably
other highly conserved genes hold much promise for phylogenetics of
Tertiary age eukaryote groups.
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Carlos Sebastián F. Kyle Satterstrom Marcia C. Haigis Raul Mostoslavsky 《The Journal of biological chemistry》2012,287(51):42444-42452
Originally rising to notoriety for their role in the regulation of aging, sirtuins are a family of NAD+-dependent enzymes that have been connected to a steadily growing set of biological processes. In addition to regulating aging, sirtuins play key roles in the maintenance of organismal metabolic homeostasis. These enzymes also have primarily protective functions in the development of many age-related diseases, including cancer, neurodegeneration, and cardiovascular disease. In this minireview, we provide an update on the known roles for each of the seven mammalian sirtuins in these areas. 相似文献
16.
The aging stress response 总被引:1,自引:0,他引:1
Aging is the outcome of a balance between damage and repair. The rate of aging and the appearance of age-related pathology are modulated by stress response and repair pathways that gradually decline, including the proteostasis and DNA damage repair networks and mitochondrial respiratory metabolism. Highly conserved insulin/IGF-1, TOR, and sirtuin signaling pathways in turn control these critical cellular responses. The coordinated action of these signaling pathways maintains cellular and organismal homeostasis in the face of external perturbations, such as changes in nutrient availability, temperature, and oxygen level, as well as internal perturbations, such as protein misfolding and DNA damage. Studies in model organisms suggest that changes in signaling can augment these critical stress response systems, increasing life span and reducing age-related pathology. The systems biology of stress response signaling thus provides a new approach to the understanding and potential treatment of age-related diseases. 相似文献
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P. Kása RW. Dames† Z. Rakonczay K. Gulya F. Joó‡ RJ. R. Wolff† 《Journal of neurochemistry》1985,44(5):1363-1372
gamma-Aminobutyric acid (GABA) was applied to the superior cervical ganglion (SCG) of CFY rats in vitro and in vivo, with or without implantation of a hypoglossal nerve, to evaluate the effects of these experimental interventions on the acetylcholine (ACh) system, which mainly serves the synaptic transmission of the preganglionic input. Long-lasting GABA microinfusion into the SCG in vivo apparently resulted in a "functional denervation." This treatment reduced the acetylcholinesterase (AChE; EC 3.1.1.7) activity by 30% (p less than 0.01) and transiently increased the number of nicotinic acetylcholine receptors, but had no significant effect on the choline acetyltransferase (acetyl-coenzyme A:choline-O-acetyltransferase; EC 2.3.1.6) activity, the ACh level, or the number of muscarinic acetylcholine receptors. The relative amounts of the different molecular forms of AChE did not change under these conditions. In vivo GABA application to the SCG with a hypoglossal nerve implanted in the presence of intact preganglionic afferent synapses exerted a significant modulatory effect on the AChE activity and its molecular forms. The "hyperinnervation" of the ganglia led to increases in the AChE activity (to 142.5%, p less than 0.01) and the 16S molecular form (to 200%, p less than 0.01). It is concluded that in vivo GABA microinfusion and GABA treatment in the presence of additional cholinergic synapses has a modulatory effect on the elements of the ACh system in the SCG of CFY rats. 相似文献
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Multiple nuclear-gene phylogenies: application to pinnipeds and comparison with a mitochondrial DNA gene phylogeny 总被引:7,自引:1,他引:7
Phylogenetic analyses of closely related species should use information
from multiple, independent genes with relatively high rates of sequence
evolution. To investigate species for which there are few prior sequence
data for single-copy nuclear (scnDNA) genes, primers for gene amplification
can be designed to highly conserved regions of exons in order to amplify
both coding (exons) and noncoding (introns) sequences. We have explored
this approach in a phylogenetic analysis of six species of pinnipeds that,
together with terrestrial carnivore outgroups, encompass divergence times
< or = 40-50 Mya. We sequenced one intron from each of the aldolase A
(ALD-A), aldolase C (ALD-C), and histone H2AF genes; one exon from the
major-histocompatibility-complex DQA gene; a H2AF processed pseudogene (psi
H2AF); and, for comparison with the nuclear genes, the 5' portion of the
mitochondrial DNA (mtDNA) control region. The pinniped psi H2AF genes were
found to be of limited use because they were paralogous with the gene in
the outgroup. The rate of silent substitution in scnDNA (primarily introns)
was 5-10-fold lower than that for mtDNA control region I, and scnDNA
sequence divergence increased linearly with time < or = 40-50 Mya.
Alleles at three polymorphic scnDNA loci (ALD-A, H2AF, and DQA) in the
southern elephant seal were paraphyletic with respect to the allele from
the closely related northern elephant seal, while the more numerous mtDNA
alleles were monophyletic. This we attribute to the consequences of a
higher mutation rate rather than to a lower effective population size of
mtDNA compared with scnDNA. Within the short (i.e., < 500-bp) sequences
of individual scnDNA sequences, phylogenetically informative variation was
insufficient to obtain robust phylogenies. However, the combined scnDNA
sequences produced a well-supported phylogeny congruent with that derived
from mtDNA. This analysis illustrates the high resolution of mtDNA
sequences compared with a similar length of scnDNA sequence, but it also
demonstrates the utility of combining information from multiple short
scnDNA sequences obtained using broadly applicable primers.
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20.