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Edith Sim Lesley A. Stanley Angela Risch Peter Thygesen 《Trends in genetics : TIG》1995,11(12):509-512
Susceptibility to multifactorial disease includes both genetic and environmental components. These two aspects of susceptibility are interlinked through genetic control of an individual's response to the environment. As a first step in identifying disease susceptibility genes that influence the response of an individual to foreign compounds (xenobiotics), it is necessary to study disorders in which there is an identified environmental trigger. Establishing a DNA resource from individuals with known environmental exposure (‘a xenogenetic register’) for diseases with an established environmental aetiology is an essential step in beginning to understand how environmental factors contribute to the susceptibility to polygenic diseases. A complementary approach to identification of environmental factors is suggested using a comparison of genetically homogeneous subdivisions of individuals with polygenic disease where there is no clue to the environmental trigger. 相似文献
63.
Monophyly of the order Rodentia inferred from mitochondrial DNA sequences of the genes for 12S rRNA, 16S rRNA, and tRNA-valine 总被引:3,自引:2,他引:1
A recent analysis of amino acid sequence data (Graur et al.) suggested that
the mammalian order Rodentia is polyphyletic, in contrast to most
morphological data, which support rodent monophyly. At issue is whether the
hystricognath rodents, such as the guinea pig, represent an independent
evolutionary lineage within mammals, separate from the sciurognath rodents.
To resolve this problem, we sequenced a region (2,645 bp) of the
mitochondrial genome of the guinea pig containing the complete 12S
ribosomal RNA, 16S ribosomal RNA, and transfer RNA(VAL) genes for
comparison with the available sciurognath and other mammalian sequences.
Several methods of analysis and statistical tests of the data all show
strong support for rodent monophyly (91%-98% bootstrap probability, or BP).
Calibration with the mammalian fossil record suggests a Cretaceous date
(107 mya) for the divergence of sciurognaths and hystricognaths. An older
date (38 mya) for the controversial Mus- Rattus divergence also is
supported by these data. Our neighbor-joining analyses of all available
sequence data (25 genes) confirm that some individual genes support rodent
polyphyly but that tandem analysis of all data does not. We propose that
the conflicting results are due to several compounding factors. The unique
biochemical properties of some hystricognath metabolic proteins, largely
responsible for generating this controversy, may have a single explanation:
a cascade effect resulting from inactivation of the zinc-binding abilities
of insulin. After excluding six genes possibly affected by insulin
inactivation, analyses of all available sequence data (7,117 nucleotide
sites, 3,099 amino acid sites) resulted in strong support for rodent
monophyly (94% BP for DNA sequences, 90% for protein sequences), which
lends support to the insulin-cascade hypothesis.
相似文献
64.
Higher-level snake phylogeny inferred from mitochondrial DNA sequences of 12S rRNA and 16S rRNA genes 总被引:3,自引:0,他引:3
Portions of two mitochondrial genes (12S and 16S ribosomal RNA) were
sequenced to determine the phylogenetic relationships among the major
clades of snakes. Thirty-six species, representing nearly all extant
families, were examined and compared with sequences of a tuatara and three
families of lizards. Snakes were found to constitute a monophyletic group
(confidence probability [CP] = 96%), with the scolecophidians (blind
snakes) as the most basal lineages (CP = 99%). This finding supports the
hypothesis that snakes underwent a subterranean period early in their
evolution. Caenophidians (advanced snakes), excluding Acrochordus, were
found to be monophyletic (CP = 99%). Among the caenophidians, viperids were
monophyletic (CP = 98%) and formed the sister group to the elapids plus
colubrids (CP = 94%). Within the viperids, two monophyletic groups were
identified: true vipers (CP = 98%) and pit vipers plus Azemiops (CP = 99%).
The elapids plus Atractaspis formed a monophyletic clade (CP = 99%). Within
the paraphyletic Colubridae, the largely Holarctic Colubrinae was found to
be a monophyletic assemblage (CP = 98%), and the Xenodontinae was found to
be polyphyletic (CP = 91%). Monophyly of the henophidians (primitive
snakes) was neither supported nor rejected because of the weak resolution
of relationships among those taxa, except for the clustering of Calabaria
with a uropeltid, Rhinophis (CP = 94%).
相似文献
65.
Cutting edge: expression of the NF of activated T cells in eosinophils: regulation by IL-4 and IL-5. 总被引:4,自引:0,他引:4
T Jinquan S Quan H H Jacobi C M Reimert A Millner J B Hansen C Thygesen L P Ryder H O Madsen H J Malling L K Poulsen 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(1):21-24
We report that NF-AT1 and NF-AT4 are expressed cytoplasmically in resting eosinophils, whereas NF-AT2 and NF-AT3 have not been seen. Likewise, NF-AT1 mRNA and NF-AT4 mRNA have been detected in resting eosinophils, and their levels can be significantly up-regulated by the Th2-associated cytokines IL-4 and IL-5. There is no detectable NF-AT protein expression in the nuclei of resting eosinophils. However NF-ATs appear in the nuclei of IL-4-, IL-5-, or ionomycin-stimulated eosinophils. Only NF-AT1 and NF-AT4, but not NF-AT2 and NF-AT3, have translocated into the nuclei in IL-4- or IL-5-stimulated eosinophils. These findings delineate a novel pathway in the cytokine network in which Th2 lymphocytes "control" eosinophils via the release of IL-4 and IL-5, and activation of NF-AT in eosinophils. The findings also suggest that a later feedback "talking" may exist between eosinophils and Th2 lymphocytes. 相似文献
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Larsen K Thygesen MB Guillaumie F Willats WG Jensen KJ 《Carbohydrate research》2006,341(10):1209-1234
Techniques involving solid supports have played crucial roles in the development of genomics, proteomics, and in molecular biology in general. Similarly, methods for immobilization or attachment to surfaces and resins have become ubiquitous in sequencing, synthesis, analysis, and screening of oligonucleotides, peptides, and proteins. However, solid-phase tools have been employed to a much lesser extent in glycobiology and glycomics. This review provides a comprehensive overview of solid-phase chemical tools for glycobiology including methodologies and applications. We provide a broad perspective of different approaches, including some well-established ones, such as immobilization in microtiter plates and to cross-linked polymers. Emerging areas such as glycan microarrays and glycan sequencing, quantum dots, and gold nanoparticles for nanobioscience applications are also discussed. The applications reviewed here include enzymology, immunology, elucidation of biosynthesis, and systems biology, as well as first steps toward solid-supported sequencing. From these methods and applications emerge a general vision for the use of solid-phase chemical tools in glycobiology. 相似文献
69.
Herbert SB Baraf Michael A Becker Sergio R Gutierrez-Urena Edward L Treadwell Janitzia Vazquez-Mellado Claudia D Rehrig Faith D Ottery John S Sundy Robert A Yood 《Arthritis research & therapy》2013,15(5):R137
Introduction
Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.Methods
Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.Results
Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).Conclusions
Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.Trial registrations
, NCT00325195 NCT01356498相似文献70.
Post ‘omic’ era has resulted in the development of many primary, secondary and derived databases. Many analytical and
visualization bioinformatics tools have been developed to manage and analyze the data available through large sequencing
projects. Availability of heterogeneous databases and tools make it difficult for researchers to access information from varied
sources and run different bioinformatics tools to get desired analysis done. Building integrated bioinformatics platforms is one of
the most challenging tasks that bioinformatics community is facing. Integration of various databases, tools and algorithm is a
challenging problem to deal with. This article describes the bioinformatics analysis workflow management systems that are
developed in the area of gene sequence analysis and phylogeny. This article will be useful for biotechnologists, molecular
biologists, computer scientists and statisticians engaged in computational biology and bioinformatics research. 相似文献