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171.
Deanna M Church Valerie A Schneider Karyn Meltz Steinberg Michael C Schatz Aaron R Quinlan Chen-Shan Chin Paul A Kitts Bronwen Aken Gabor T Marth Michael M Hoffman Javier Herrero M Lisandra Zepeda Mendoza Richard Durbin Paul Flicek 《Genome biology》2015,16(1)
The human genome reference assembly is crucial for aligning and analyzing sequence data, and for genome annotation, among other roles. However, the models and analysis assumptions that underlie the current assembly need revising to fully represent human sequence diversity. Improved analysis tools and updated data reporting formats are also required. 相似文献
172.
Contrasting genetic diversity and population structure among three sympatric Madagascan shorebirds: parallels with rarity,endemism, and dispersal 下载免费PDF全文
Luke J. Eberhart‐Phillips Joseph I. Hoffman Edward G. Brede Sama Zefania Martina J. Kamrad Tamás Székely Michael W. Bruford 《Ecology and evolution》2015,5(5):997-1010
Understanding the relative contributions of intrinsic and extrinsic factors to population structure and genetic diversity is a central goal of conservation and evolutionary genetics. One way to achieve this is through comparative population genetic analysis of sympatric sister taxa, which allows evaluation of intrinsic factors such as population demography and life history while controlling for phylogenetic relatedness and geography. We used ten conserved microsatellites to explore the population structure and genetic diversity of three sympatric and closely related plover species in southwestern Madagascar: Kittlitz's plover (Charadrius pecuarius), white‐fronted plover (C. marginatus), and Madagascar plover (C. thoracicus). Bayesian clustering revealed strong population structure in the rare and endemic Madagascar plover, intermediate population structure in the white‐fronted plover, and no detectable population structure in the geographically widespread Kittlitz's plover. In contrast, allelic richness and heterozygosity were highest for the Kittlitz's plover, intermediate for the white‐fronted plover and lowest for the Madagascar plover. No evidence was found in support of the “watershed mechanism” proposed to facilitate vicariant divergence of Madagascan lemurs and reptiles, which we attribute to the vagility of birds. However, we found a significant pattern of genetic isolation by distance among populations of the Madagascar plover, but not for the other two species. These findings suggest that interspecific variation in rarity, endemism, and dispersal propensity may influence genetic structure and diversity, even in highly vagile species. 相似文献
173.
Weiss HA Paz Bailey G Phiri S Gresenguet G LeGoff J Pepin J Lewis DA Belec L Hoffman IF Miller WC Mayaud P 《PloS one》2011,6(7):e22601
Background
A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations.Methodology/Principal Findings
Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm2), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors.Conclusions/Significance
There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing. 相似文献174.
Hoffman GG Ellington WR 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2011,6(2):171-177
The genome of the choanoflagellate Monosiga brevicollis contains at least three genes for the phosphoryl transfer enzyme, arginine kinase (AK; EC 2.7.3.3). Bioinformatic analyses of the deduced amino acid sequences of the proteins coded for by two of these genes showed that one of these AKs is cytoplasmic (denoted AK1) while the other appears to have an N-terminal mitochondrial targeting peptide (denoted AK2). Cloning and expression of the cDNA for AK1 yielded considerable soluble AK activity. Three AK2 constructs were expressed - one corresponding to the full length protein and two corresponding to truncated versions in which the signal peptide had been deleted. Expression of the former construct yielded minimal soluble activity. In contrast, significant AK activity was found in both truncated constructs confirming the importance of removal of the targeting peptide for proper folding and catalytic activity. Both AK1 and AK2 are functional oligomers unlike typical AKs which are monomeric. A phylogenetic analysis showed that these choanoflagellate AKs group more closely with a supercluster consisting of cytoplasmic and mitochondrial CKs and invertebrate AKs that evolved secondarily from a CK-like ancestor. Reaction-diffusion constraints in choanoflagellates are likely mitigated by the presence of AK isoforms which facilitate energy transport in these highly polarized cells. 相似文献
175.
Retrovirus-mediated transfer of an adenovirus gene encoding an integral membrane protein is sufficient to down regulate the receptor for epidermal growth factor. 总被引:7,自引:1,他引:7 下载免费PDF全文
We have used retrovirus-mediated gene transfer to introduce sequences encoding a 10,400-molecular-weight (10.4K) adenovirus protein previously shown to down regulate the receptor for epidermal growth factor (EGF) into two murine cell lines that possess human EGF receptors (EGF-Rs). Assays for receptor expression showed that acute infection resulted in rapid, constitutive down regulation of the EGF-R via a pathway that appears to be endosome mediated. This represents the first demonstration that 10.4K expression in the absence of other virus-encoded proteins is sufficient to elicit this response. The usefulness of this approach for the study of 10.4K-mediated signal transduction in cells with a nontransformed phenotype is discussed. 相似文献
176.
Yukihiko Hiroshima Yong Zhang Nan Zhang Ali Maawy Sumiyuki Mii Mako Yamamoto Fuminari Uehara Shinji Miwa Shuya Yano Takashi Murakami Masashi Momiyama Takashi Chishima Kuniya Tanaka Yasushi Ichikawa Michael Bouvet Takuya Murata Itaru Endo Robert M. Hoffman 《PloS one》2015,10(2)
Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient’s cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient’s cervical tumors resulted in primary growth but not metastasis. 相似文献
177.
The role of membrane phosphoglycerate kinase in the control of glycolytic rate by active cation transport in human red blood cells 总被引:12,自引:5,他引:12 下载免费PDF全文
When the internal Na of human red cells is raised, both K influx and lactate production increase and become more sensitive to the inhibitory action of ouabain. This occurs with either glucose or purine nucleoside as substrate. Fresh whole hemolysates enriched with Na and Mg will convert intermediates above the triose phosphate dehydrogenase step to lactate at a rate which is slowed by ouabain. Intermediates beyond the phosphoglycerate kinase step (PGK) are metabolized at a very rapid rate which is not affected by ouabain. No metabolic effects of ouabain were found in ghost-free hemolysates. Hemoglobin-free ghosts were shown to have both triose phosphate dehydrogenase and PGK activity. The rate of this two-enzyme sequence was found to be a function of the ADP concentration, being maximal when ADP > 0.35 mM. Initial addition of ATP to the ghost system rendered the forward rate of the sequence sensitive to the inhibitory action of ouabain. When the sequence was run in reverse, no inhibitory effect of ouabain could be demonstrated. It is concluded that membrane PGK is a point at which the Na-K transport system can influence the metabolic rate and that this action is possibly exerted via a compartmentalized form of ADP which is an immediate substrate for the ghost PGK. 相似文献
178.
Subthreshold-activating A-type K(+) currents are essential for the proper functioning of the brain, where they act to delay excitation and regulate firing frequency. In CA1 hippocampal pyramidal neuron dendrites, the density of A-type K(+) current increases with distance from the soma, playing an important role in synaptic integration and plasticity. The mechanism underlying this gradient has, however, remained elusive. Here, dendritic recordings from mice lacking the Kv4 transmembrane auxiliary subunit DPP6 revealed that this protein is critical for generating the A-current gradient. Loss of DPP6 led to a decrease in A-type current, specifically in distal dendrites. Decreased current density was accompanied by a depolarizing shift in the voltage dependence of channel activation. Together these changes resulted in hyperexcitable dendrites with enhanced dendritic AP back-propagation, calcium electrogenesis, and induction of synaptic long-term potentiation. Despite enhanced dendritic excitability, firing behavior evoked by somatic current injection was mainly unaffected in DPP6-KO recordings, indicating compartmentalized regulation of neuronal excitability. 相似文献
179.
180.
A. Kleinhofs A. Kilian M. A. Saghai Maroof R. M. Biyashev P. Hayes F. Q. Chen N. Lapitan A. Fenwick T. K. Blake V. Kanazin E. Ananiev L. Dahleen D. Kudrna J. Bollinger S. J. Knapp B. Liu M. Sorrells M. Heun J. D. Franckowiak D. Hoffman R. Skadsen B. J. Steffenson 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1993,86(6):705-712
A map of the barley genome consisting of 295 loci was constructed. These loci include 152 cDNA restriction fragment length polymorphism (RFLP), 114 genomic DNA RFLP, 14 random amplified polymorphic DNA (RAPD), five isozyme, two morphological, one disease resistance and seven specific amplicon polymorphism (SAP) markers. The RFLP-identified loci include 63 that were detected using cloned known function genes as probes. The map covers 1,250 centiMorgans (cM) with a 4.2 cM average distance between markers. The genetic lengths of the chromosomes range from 124 to 223 cM and are in approximate agreement with their physical lengths. The centromeres were localized to within a few markers on all of the barley chromosomes except chromosome 5. Telomeric regions were mapped for the short (plus) arms of chromosomes 1, 2 and 3 and the long (minus) arm of chromosomes 7.This research was also supported by other members of the NABGMP: K. Kasha, Department of Crop Science, University of Guelph, Guelph, Ontario, Canada NIG 2W1; W. Kim, Agriculture Canada Research Station, 195 Dafoe Road, Winnipeg, Manitoba, Canada R3T 2M9; A. Laroche, Agriculture Canada Research Station, P.O. Box 3000 Main, Lethbridge, Alberta, Canada,TU 4B1; S. Molnar, Plant Research Centre Agriculture Canada, Central Experimental farm, Ottawa, Ontario, Canada K1A 0C6; G. Scoles, Department of Crop Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N OWOThis research is part of the North American Barley Genome Mapping Project, R. A. Nilan and K. Kasha, Coordinator and Associate Coordinator, respectively
Permanent address: Department of Plant Genetics, NI Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 相似文献