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41.
A genomewide search finds major susceptibility loci for gallbladder disease on chromosome 1 in Mexican Americans 总被引:5,自引:0,他引:5 下载免费PDF全文
Puppala S Dodd GD Fowler S Arya R Schneider J Farook VS Granato R Dyer TD Almasy L Jenkinson CP Diehl AK Stern MP Blangero J Duggirala R 《American journal of human genetics》2006,78(3):377-392
Gallbladder disease (GBD) is one of the major digestive diseases. Its risk factors include age, sex, obesity, type 2 diabetes, and metabolic syndrome (MS). The prevalence of GBD is high in minority populations, such as Native and Mexican Americans. Ethnic differences, familial aggregation of GBD, and the identification of susceptibility loci for gallstone disease by use of animal models suggest genetic influences on GBD. However, the major susceptibility loci for GBD in human populations have not been identified. Using ultrasound-based information on GBD occurrence and a 10-cM gene map, we performed multipoint variance-components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in the San Antonio Family Diabetes/Gallbladder Study were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. With use of the National Cholesterol Education Program/Adult Treatment Panel III criteria, five MS risk factors were defined: increased waist circumference, hypertriglyceredemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The MS risk-factor score (range 0-5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and MS risk-factor score, we found stronger linkage signals for the symptomatic GBD phenotype. The highest LOD scores (3.7 and 3.5) occurred on chromosome 1p between markers D1S1597 and D1S407 (1p36.21) and near marker D1S255 (1p34.3), respectively. Other genetic locations (chromosomes 2p, 3q, 4p, 8p, 9p, 10p, and 16q) across the genome exhibited some evidence of linkage (LOD >or=1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of Lith loci, which influence gallstone formation in mouse models. In conclusion, we found significant evidence of major genetic determinants of symptomatic GBD on chromosome 1p in Mexican Americans. 相似文献
42.
Response of Campylobacter jejuni to combinations of ferrous sulphate and cadmium chloride 总被引:1,自引:0,他引:1
N.J. Stern S.U. Kazmi B.S. Roberson† K. Ono‡ B.J. Juven§ 《Journal of applied microbiology》1988,64(3):247-256
On Mueller Hinton (MH) agar, Campylobacter jejuni showed 20.0 and 30.9mm zones of inhibition surrounding discs impregnated with 2.5 and 20 μg CdCl2 respectively. The minimal inhibitory concentration (MIC) ranged from 0.64 to 3.2 μg CdCl2 /ml of MH agar for four C. jejuni strains. In the presence of 23 μg FeSO4 /ml of MH the MIC increased to a range of 1.5–5.4 μg CdCl2 /ml of MH. Moreover, the numbers of colonies present on MH supplemented with FeSO4 were greater than on MH without iron. The growth response of C. jejuni in the presence of 0.025% (w/v) FeSO4 in MH broth was increased about 10000 fold in three of four strains when compared with the growth in unsupplemented MH broth. Zones of inhibition surrounding 20 μg discs of CdCl2 were 50.6 and 24.4 mm on MH and Campy-BAP media respectively, with cells grown on MH. These results suggest that the blood-containing medium 'neutralized' the biocidal influence of the CdCl2 . In comparison, C. jejuni inoculum from fluid thioglycollate (FT) medium showed smaller zones of inhibition. These decreased from 34.9 mm on MH agar to 19.6 mm on Campy-BAP agar, suggesting that components in the FT growth medium ameliorated the toxic influence of CdCl2 . Atomic absorption spectroscopy analysis indicated mean values (mg/100 g dry weight) of selected metals bound by C. jejuni as: Cu, 10.4; Mg, 146; Na, 2385; Fe, 45.1; Zn, 13.0; and K, 172. 相似文献
43.
44.
The atomic environment around the iron site in the nonheme iron sulfur protein rubredoxin was studied by the extended X-ray absorption fine structure (EXAFS) technique. Within experimental error, the Fe-S bonds in oxidized Clostridium pasteurianum rubredoxin are the same as in the analogue anion [Fe(S2-o-xyl)2]-synthesized by Holm. The average Fe-S bond length is 2.267 +/- 0.003A and the root mean square deviation about this average due to structural disorder is 0.032 + 0.013 - 0.032. 相似文献
45.
Marc Yudkoff Yevgeny Daikhin Zhi-Ping Lin Liana Nissim Janet Stern David Pleasure Itzhak Nissim 《Journal of neurochemistry》1994,62(3):1192-1202
Abstract: The aim was to study the extent to which leu-cine furnishes α-NH2 groups for glutamate synthesis via branched-chain amino acid aminotransferase. The transfer of N from leucine to glutamate was determined by incubating astrocytes in a medium containing [15N]leucine and 15 unlabeled amino acids; isotopic abundance was measured with gas chromatography-mass spectrometry. The ratio of labeling in both [15N]glutamate/[15N]leucine and [2-15N]glutamine/[15N]leucine suggested that at least one-fifth of all glutamate N had been derived from leucine nitrogen. At the same time, enrichment in [15N]leucine declined, reflecting dilution of the 16N label by the unlabeled amino acids that were in the medium. Isotopic abundance in [16N]-isoleucine increased very quickly, suggesting the rapidity of transamination between these amino acids. The appearance of 15N in valine was more gradual. Measurement of branched-chain amino acid transaminase showed that the reaction from leucine to glutamate was approximately six times more active than from glutamate to leucine (8.72 vs. 1.46 nmol/min/mg of protein). However, when the medium was supplemented with α-ketoisocaproate (1 mM), the ketoacid of leucine, the reaction readily ran in the “reverse” direction and intraastrocytic [glutamate] was reduced by ~50% in only 5 min. Extracellular concentrations of α-ketoisocaproate as low as 0.05 mM significantly lowered intracellular [glutamate]. The relative efficiency of branched-chain amino acid transamination was studied by incubating astrocytes with 15 unlabeled amino acids (0.1 mM each) and [15N]glutamate. After 45 min, the most highly labeled amino acid was [15N]alanine, which was closely followed by [15N]leucine and [15N]isoleucine. Relatively little 15N was detected in any other amino acids, except for [15N]serine. The transamination of leucine was ~17 times greater than the rate of [1-14C]leucine oxidation. These data indicate that leucine is a major source of glutamate nitrogen. Conversely, reamination of a-ketoisocaproate, the ketoacid of leucine, affords a mechanism for the temporary “buffering” of intracellular glutamate. 相似文献
46.
Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis 总被引:1,自引:0,他引:1
Group B and C Neisseria meningitidis are the major cause of meningococcal
disease in the United States and in Europe. N . meningitidis
lipooligosaccharide (LOS), a major surface antigen, can be divided into 12
immunotypes of which L1 through L8 were found among Group B and C
organisms. Groups B and C but not Group A may sialylate their LOSs with
N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they
synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as
probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4,
L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis
leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc
sequence, but not to Sambucus nigra agglutinin, which binds
NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot
analyses revealed that these six LOSs contained only the
NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS
components, which have a common terminal lacto-N-neotetraose (LNnT,
Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown
by previous studies. The LOS-lectin binding was abolished when the LOSs
were treated with Newcastle disease viral neuraminidase which cleaves
alpha2-->3 linked sialic acid. Methylation analysis of a representative
LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs
structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide)
and sialylparagloboside and some glycoproteins in having LNnT and
N-acetyllactosamine sequences, respectively, with or without alpha2-->3
linked NeuNAc. The molecular mimicry of the LOSs may play a role in the
pathogenesis of N.meningitidis by assisting the organism to evade host
immune defenses in man.
相似文献
47.
Evaluating the Ribosomal Internal Transcribed Spacer (ITS) as a Candidate Dinoflagellate Barcode Marker 总被引:4,自引:0,他引:4
RF Stern RA Andersen I Jameson FC Küpper MA Coffroth D Vaulot F Le Gall B Véron JJ Brand H Skelton F Kasai EL Lilly PJ Keeling 《PloS one》2012,7(8):e42780
Background
DNA barcoding offers an efficient way to determine species identification and to measure biodiversity. For dinoflagellates, an ancient alveolate group of about 2000 described extant species, DNA barcoding studies have revealed large amounts of unrecognized species diversity, most of which is not represented in culture collections. To date, two mitochondrial gene markers, Cytochrome Oxidase I (COI) and Cytochrome b oxidase (COB), have been used to assess DNA barcoding in dinoflagellates, and both failed to amplify all taxa and suffered from low resolution. Nevertheless, both genes yielded many examples of morphospecies showing cryptic speciation and morphologically distinct named species being genetically similar, highlighting the need for a common marker. For example, a large number of cultured Symbiodinium strains have neither taxonomic identification, nor a common measure of diversity that can be used to compare this genus to other dinoflagellates.Methodology/Principal Findings
The purpose of this study was to evaluate the Internal Transcribed Spacer units 1 and 2 (ITS) of the rDNA operon, as a high resolution marker for distinguishing species dinoflagellates in culture. In our study, from 78 different species, the ITS barcode clearly differentiated species from genera and could identify 96% of strains to a known species or sub-genus grouping. 8.3% showed evidence of being cryptic species. A quarter of strains identified had no previous species identification. The greatest levels of hidden biodiversity came from Scrippsiella and the Pfiesteriaceae family, whilst Heterocapsa strains showed a high level of mismatch to their given species name.Conclusions/Significance
The ITS marker was successful in confirming species, revealing hidden diversity in culture collections. This marker, however, may have limited use for environmental barcoding due to paralogues, the potential for unidentifiable chimaeras and priming across taxa. In these cases ITS would serve well in combination with other markers or for specific taxon studies. 相似文献48.
Hot topic or hot air? Climate change and malaria resurgence in East African highlands 总被引:1,自引:0,他引:1
Hay SI Rogers DJ Randolph SE Stern DI Cox J Shanks GD Snow RW 《Trends in parasitology》2002,18(12):530-534
Climate has a significant impact on malaria incidence and we have predicted that forecast climate changes might cause some modifications to the present global distribution of malaria close to its present boundaries. However, it is quite another matter to attribute recent resurgences of malaria in the highlands of East Africa to climate change. Analyses of malaria time-series at such sites have shown that malaria incidence has increased in the absence of co-varying changes in climate. We find the widespread increase in resistance of the malaria parasite to drugs and the decrease in vector control activities to be more likely driving forces behind the malaria resurgence. 相似文献
49.
Stern LE Falcone RA Kemp CJ Braun MC Erwin CR Warner BW 《American journal of physiology. Gastrointestinal and liver physiology》2000,278(6):G871-G877
Salivary epidermal growth factor (sEGF) levels are increased in male mice after small bowel resection (SBR) and may be important during intestinal adaptation. Since males have greater sEGF than females, the influence of sex on postresection adaptation was tested. Females had lower sEGF; however, sEGF substantially increased in both sexes after a massive (50%) SBR. Adaptive increases in DNA and protein content, villus height, and crypt depth, as well as crypt cell proliferation rates in the remnant ileum, were not different between males and females. Although significant postresection increases in sEGF were identified, EGF mRNA and protein did not change within the submandibular gland. Glandular kallikrein-13 and ileal EGF receptor expression were greater after SBR in female mice. Intestinal adaptation is equivalent in female and male mice after SBR. Despite lower sEGF, females demonstrated increased expression of a kallikrein responsible for sEGF precursor cleavage as well as amplified ileal EGF receptor expression. These results endorse an important differential response between sexes regarding sEGF mobilization and intestinal receptor availability during adaptation. 相似文献
50.
Nathalie Jeanray Rapha?l Marée Benoist Pruvot Olivier Stern Pierre Geurts Louis Wehenkel Marc Muller 《PloS one》2015,10(1)
Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo survival and development are generally evaluated manually through microscopic observation by an expert and documented by several typical photographs. Here, we present a methodology to automatically classify brightfield images of wildtype zebrafish embryos according to their defects by using an image analysis approach based on supervised machine learning. We show that, compared to manual classification, automatic classification results in 90 to 100% agreement with consensus voting of biological experts in nine out of eleven considered defects in 3 days old zebrafish larvae. Automation of the analysis and classification of zebrafish embryo pictures reduces the workload and time required for the biological expert and increases the reproducibility and objectivity of this classification. 相似文献