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21.
Han Y Gu S Oota H Osier MV Pakstis AJ Speed WC Kidd JR Kidd KK 《American journal of human genetics》2007,80(3):441-456
The alcohol dehydrogenase (ADH) family of enzymes catalyzes the reversible oxidation of alcohol to acetaldehyde. Seven ADH genes exist in a segment of ~370 kb on 4q21. Products of the three class I ADH genes that share 95% sequence identity are believed to play the major role in the first step of ethanol metabolism. Because the common belief that selection has operated at the ADH1B*47His allele in East Asian populations lacks direct biological or statistical evidence, we used genomic data to test the hypothesis. Data consisted of 54 single-nucleotide polymorphisms (SNPs) across the ADH clusters in a global sampling of 42 populations. Both the F(st) statistic and the long-range haplotype (LRH) test provided positive evidence of selection in several East Asian populations. The ADH1B Arg47His functional polymorphism has the highest F(st) of the 54 SNPs in the ADH cluster, and it is significantly above the mean F(st) of 382 presumably neutral sites tested on the same 42 population samples. The LRH test that uses cores including that site and extending on both sides also gives significant evidence of positive selection in some East Asian populations for a specific haplotype carrying the ADH1B*47His allele. Interestingly, this haplotype is present at a high frequency in only some East Asian populations, whereas the specific allele also exists in other East Asian populations and in the Near East and Europe but does not show evidence of selection with use of the LRH test. Although the ADH1B*47His allele conveys a well-confirmed protection against alcoholism, that modern phenotypic manifestation does not easily translate into a positive selective force, and the nature of that selective force, in the past and/or currently, remains speculative. 相似文献
22.
Sumi Biswas Prateek Choudhary Sean C. Elias Kazutoyo Miura Kathryn H. Milne Simone C. de Cassan Katharine A. Collins Fenella D. Halstead Carly M. Bliss Katie J. Ewer Faith H. Osier Susanne H. Hodgson Christopher J. A. Duncan Geraldine A. O’Hara Carole A. Long Adrian V. S. Hill Simon J. Draper 《PloS one》2014,9(9)
The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite – MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors – ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases targets, these data should help to guide further immuno-monitoring studies of vaccine-induced human antibody responses. 相似文献
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In vertebrates and the cephalochordate, amphioxus, the closest vertebrate
relative, Hox genes are linked in a single cluster. Accompanying the
emergence of higher vertebrates, the Hox gene cluster duplicated in either
a single step or multiple steps, resulting in the four-cluster state
present in teleosts and tetrapods. Mammalian Hox clusters (designated A, B,
C, and D) extend over 100 kb and are located on four different chromosomes.
Reconstructing the history of the duplications and its relation to
vertebrate evolution has been problematic due to the lack of alignable
sequence information. In this study, the problem was approached by
conducting a statistical analysis of sequences from the fibrillar-type
collagens (I, II, III, and IV), genes closely linked to each Hox cluster
which likely share the same duplication history as the Hox genes. We find
statistical support for the hypothesis that the cluster duplication
occurred as multiple distinct events and that the four-cluster situation
arose by a three- step sequential process.
相似文献
25.
Olga Pivovarova Christian von Loeffelholz Iryna Ilkavets Carsten Sticht Sergei Zhuk Veronica Murahovschi Sonja Lukowski Stephanie D?cke Jennifer Kriebel Tonia de las Heras Gala Anna Malashicheva Anna Kostareva Johan F Lock Martin Stockmann Harald Grallert Norbert Gretz Steven Dooley Andreas FH Pfeiffer Natalia Rudovich 《Cell cycle (Georgetown, Tex.)》2015,14(14):2293-2300
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28.
M Onderci K Sahin N Sahin MF Gursu D Doerge FH Sarkar 《Archives of animal nutrition》2013,67(6):463-471
Genistein, a phytoestrogen found in soybeans, is a powerful antioxidant. We evaluated the effects of genistein supplementation on performance, carcass characteristics, levels of malondialdehyde (MDA), homocysteine, vitamins C, E, A in Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature of 34°C. Two hundred and forty Japanese quails (10 d old) were randomly assigned to eight treatment groups consisting of 10 replicates of three birds. The birds were kept in an environmental controlled room either for 24 h/d at 22°C with (thermoneutral, TN groups) or for 16 h/d at 22°C and for 8 h/d (09.00 am to 05.00 pm) at 34°C (heat stress, HS groups). Birds were fed either a basal (control) diet (TN and HS) or the basal diet supplemented with 200, 400 or 800 mg of genistein per kg of diet. Heat exposure decreased birds' performance when basal diet was fed. Increase in feed intake and body weight, and improvement of feed efficiency and carcass traits were found in genistein-supplemented quails reared under heat stress conditions. Growth rate and feed efficiency improved in quails reared under thermo-neutral conditions as well. Concentration of serum vitamins C, E, and A increased in supplemented birds reared at high temperature, while non-significant changes occurred in TN groups. With genistein supplementation homocysteine levels in serum and MDA levels in serum and liver decreased in all birds of both TN and HS groups. Effects of genistein were relatively greater in heat-stressed quails than in quails kept under thermo-neutral conditions. Results of the present study suggest that supplementation with genistein can be considered to be protective by reducing the negative effects of oxidative stress induced by heat stress in quail. 相似文献
29.
Gathoni Kamuyu Christian Bottomley James Mageto Brett Lowe Patricia P. Wilkins John C. Noh Thomas B. Nutman Anthony K. Ngugi Rachael Odhiambo Ryan G. Wagner Angelina Kakooza-Mwesige Seth Owusu-Agyei Kenneth Ae-Ngibise Honorati Masanja Faith H. A. Osier Peter Odermatt Charles R. Newton 《PLoS neglected tropical diseases》2014,8(5)
Background
Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa.Methods and Findings
A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52–2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23–1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04–1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30–2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas.Conclusion
This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated. 相似文献30.
Urine metabolomic analysis identifies potential biomarkers and pathogenic pathways in kidney cancer 总被引:1,自引:0,他引:1
Kim K Taylor SL Ganti S Guo L Osier MV Weiss RH 《Omics : a journal of integrative biology》2011,15(5):293-303
Kidney cancer is the seventh most common cancer in the Western world, its incidence is increasing, and it is frequently metastatic at presentation, at which stage patient survival statistics are grim. In addition, there are no useful biofluid markers for this disease, such that diagnosis is dependent on imaging techniques that are not generally used for screening. In the present study, we use metabolomics techniques to identify metabolites in kidney cancer patients' urine, which appear at different levels (when normalized to account for urine volume and concentration) from the same metabolites in nonkidney cancer patients. We found that quinolinate, 4-hydroxybenzoate, and gentisate are differentially expressed at a false discovery rate of 0.26, and these metabolites are involved in common pathways of specific amino acid and energetic metabolism, consistent with high tumor protein breakdown and utilization, and the Warburg effect. When added to four different (three kidney cancer-derived and one "normal") cell lines, several of the significantly altered metabolites, quinolinate, α-ketoglutarate, and gentisate, showed increased or unchanged cell proliferation that was cell line-dependent. Further evaluation of the global metabolomics analysis, as well as confirmation of the specific potential biomarkers using a larger sample size, will lead to new avenues of kidney cancer diagnosis and therapy. 相似文献