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Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
3.
T. M. MacDonald S. V. Morant G. C. Robinson M. J. Shield M. M. McGilchrist F. E. Murray D. G. McDevitt 《BMJ (Clinical research ed.)》1997,315(7119):1333-1337
OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs. 相似文献
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Kevin D. Shield Gerrit Gmel Tara Kehoe-Chan Deborah A. Dawson Bridget F. Grant Jürgen Rehm 《PloS one》2013,8(1)
Background
Alcohol has been linked to health disparities between races in the US; however, race-specific alcohol-attributable mortality has never been estimated. The objective of this article is to estimate premature mortality attributable to alcohol in the US in 2005, differentiated by race, age and sex for people 15 to 64 years of age.Methods and Findings
Mortality attributable to alcohol was estimated based on alcohol-attributable fractions using indicators of exposure from the National Epidemiologic Survey on Alcohol and Related Conditions and risk relations from the Comparative Risk Assessment study. Consumption data were corrected for undercoverage (the observed underreporting of alcohol consumption when using survey as compared to sales data) using adult per capita consumption from WHO databases. Mortality data by cause of death were obtained from the US Department of Health and Human Services. For people 15 to 64 years of age in the US in 2005, alcohol was responsible for 55,974 deaths (46,461 for men; 9,513 for women) representing 9.0% of all deaths, and 1,288,700 PYLL (1,087,280 for men; 201,420 for women) representing 10.7% of all PYLL. Per 100,000 people, this represents 29 deaths (29 for White; 40 for Black; 82 for Native Americans; 6 for Asian/Pacific Islander) and 670 PYLL (673 for White; 808 for Black; 1,808 for Native American; 158 for Asian/Pacific Islander). Sensitivity analyses showed a lower but still substantial burden without adjusting for undercoverage.Conclusions
The burden of mortality attributable to alcohol in the US is unequal among people of different races and between men and women. Racial differences in alcohol consumption and the resulting harms explain in part the observed disparities in the premature mortality burden between races, suggesting the need for interventions for specific subgroups of the population such as Native Americans. 相似文献6.
Background
In addition to known protein-coding genes, large amounts of apparently non-coding sequence are conserved between the human and mouse genomes. It seems reasonable to assume that these conserved regions are more likely to contain functional elements than less-conserved portions of the genome. 相似文献7.
van Dijken JP Bauer J Brambilla L Duboc P Francois JM Gancedo C Giuseppin ML Heijnen JJ Hoare M Lange HC Madden EA Niederberger P Nielsen J Parrou JL Petit T Porro D Reuss M van Riel N Rizzi M Steensma HY Verrips CT Vindeløv J Pronk JT 《Enzyme and microbial technology》2000,26(9-10):706-714
To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation. 相似文献
8.
9.
Shield JP 《Hormone research》2007,67(2):77-83
It has become increasingly apparent over the last few years that the seemingly ubiquitous auto-immune aetiology to pre-pubertal diabetes does not apply to those diagnosed under 6 months of age. In this age group, disease appears, in the vast majority of cases, to be conferred by single gene disorders mainly related to pancreatic development. The unravelling of these disorders has resulted in a far greater understanding of pancreatic development and some startling changes in treatment, resulting in improved quality of life and diabetes control. The progress made in our scientific and clinical understanding of these extremely rare diseases is a perfect example of how studying seemingly rare illnesses can improve our overall knowledge of much more common conditions. 相似文献
10.
E.?Tapia-VenegasEmail author L.?Cabrol B.?Brandhoff J.?Hamelin E.?Trably JP?Steyer G.?Ruiz-Filippi 《Applied microbiology and biotechnology》2015,99(19):8295-8308
Hydrogen is a promising alternative as an energetic carrier and its production by dark fermentation from wastewater has been recently proposed, with special attention to crude glycerol as potential substrate. In this study, two different feeding strategies were evaluated for replacing the glucose substrate by glycerol substrate: a one-step strategy (glucose was replaced abruptly by glycerol) and a step-by-step strategy (progressive decrease of glucose concentration and increase of glycerol concentration from 0 to 5 g L?1), in a continuous stirred tank reactor (12 h of hydraulic retention time (HRT), pH 5.5, 35 °C). While the one-step strategy led to biomass washout and unsuccessful H2 production, the step-by-step strategy was efficient for biomass adaptation, reaching acceptable hydrogen yields (0.4?±?0.1 molH2?mol?1 glycerol consumed) around 33 % of the theoretical yield independently of the glycerol concentration. Microbial community structure was investigated by single-strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) fingerprinting techniques, targeting either the total community (16S ribosomal RNA (rRNA) gene) or the functional Clostridium population involved in H2 production (hydA gene), as well as by 454 pyrosequencing of the total community. Multivariate analysis of fingerprinting and pyrosequencing results revealed the influence of the feeding strategy on the bacterial community structure and suggested the progressive structural adaptation of the community to increasing glycerol concentrations, through the emergence and selection of specific species, highly correlated to environmental parameters. Particularly, this work highlighted an interesting shift of dominant community members (putatively responsible of hydrogen production in the continuous stirred tank reactor (CSTR)) according to the gradient of glycerol proportion in the feed, from the family Veillonellaceae to the genera Prevotella and Clostridium sp., putatively responsible of hydrogen production in the CSTR. 相似文献