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1.
The ATP-binding-cassette transmembrane transporters (ABC transporters)
known from vertebrates belong to four major subfamilies: (1) the P-
glycoproteins (Pgp); (2) the cystic fibrosis transmembrane conductance
regulators (CFTR); (3) the Tap proteins encoded with the major
histocompatibility complex of mammals; and (4) the peroxisomal membrane
proteins. Both Pgp and CFTR have a structure suggesting a past internal
gene duplication; a phylogenetic analysis indicated that these duplications
occurred independently, while an independent tandem gene duplication
occurred in the case of the Tap family. Both the Pgp and Tap proteins show
evidence of relationship to bacterial ABC transporters lacking internal
duplication, and both are significantly more closely related to the HlyB
and MsbA families of transporters from purple bacteria than they are to ABC
transporters from nonpurple bacteria. The simplest hypothesis to explain
this observation is that eukaryotic Pgp and Tap genes are descended from a
mitochondrial gene or genes that were subsequently translocated to the
nuclear genome. The Pgp genes of eukaryotes are characterized by a
remarkable degree of convergent evolution between the ATP-binding cassettes
of their N- terminal and C-terminal halves, whereas no such convergence is
seen between the two halves of CFTR genes or between the duplicated Tap
genes. Exon 13 of the CFTR gene, which encodes a putative regulatory domain
not found in other ABC transporters apart from CFTR, showed high levels of
both synonymous and nonsynonymous difference in comparisons among different
mammalian species, suggesting that this region is a mutational hot spot.
相似文献
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3.
X Xiao G Hintermann AL Demanin J Piret 《Journal of industrial microbiology & biotechnology》1996,16(4):261-262
Streptomyces glaucescens is shown to possess -lactamase activity which is inhibitable by clavulanate. This is important in regard to its use as a cloning host for enzymes of \-lactam biosynthesis. 相似文献
4.
ERIC S. BONO PATRICK SMOLINSKI AL CASAGRANDA JUNDE XU 《Computer methods in biomechanics and biomedical engineering》2013,16(2):125-131
The Shear-slip Mesh Update Method (SSMUM) is being used in flow simulations involving large but regular displacements of one or more boundaries of the computational domain. We follow up the earlier discussion of the method with notes on practical implementation aspects. In order to establish a benchmark problem for this class of flow problems, we define and report results from a two-dimensional viscous flow around a rotating stirrer in a square chamber. The application potential of the method is demonstrated in the context of biomedical design problem, as we perform an analysis of blood flow in a centrifugal left ventricular assist device, or blood pump, which involves a rotating impeller in a non-axisymmetric housing. 相似文献
5.
6.
HENRY SILVERMAN BABIKER AHMED SAMAR AJEILET SUMAIA AL‐FADIL SUHAIL AL‐AMAD HADIR EL‐DESSOUKY IBRAHIM EL‐GENDY MOHAMED EL‐GUINDI MUSTAFA EL‐NIMEIRI RANA MUZAFFAR AZZA SALEH 《Developing world bioethics》2010,10(2):70-77
To help ensure the ethical conduct of research, many have recommended educational efforts in research ethics to investigators and members of research ethics committees (RECs). One type of education activity involves multi‐day workshops in research ethics. To be effective, such workshops should contain the appropriate content and teaching techniques geared towards the learning styles of the targeted audiences. To ensure consistency in content and quality, we describe the development of a curriculum guide, core competencies and associated learning objectives and activities to help educators organize research ethics workshops in their respective institutions. The curriculum guide is divided into modular units to enable planners to develop workshops of different lengths and choose content materials that match the needs, abilities, and prior experiences of the target audiences. The content material in the curriculum guide is relevant for audiences in the Middle East, because individuals from the Middle East who participated in a Certificate Program in research ethics selected and developed the training materials (e.g., articles, powerpoint slides, case studies, protocols). Also, many of the activities incorporate active‐learning methods, consisting of group work activities analyzing case studies and reviewing protocols. The development of such a workshop training curriculum guide represents a sustainable educational resource to enhance research ethics capacity in the Middle East. 相似文献
7.
Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development 总被引:10,自引:0,他引:10
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Gangloff YG Mueller M Dann SG Svoboda P Sticker M Spetz JF Um SH Brown EJ Cereghini S Thomas G Kozma SC 《Molecular and cellular biology》2004,24(21):9508-9516
The mammalian target of rapamycin (mTOR) is a key component of a signaling pathway which integrates inputs from nutrients and growth factors to regulate cell growth. Recent studies demonstrated that mice harboring an ethylnitrosourea-induced mutation in the gene encoding mTOR die at embryonic day 12.5 (E12.5). However, others have shown that the treatment of E4.5 blastocysts with rapamycin blocks trophoblast outgrowth, suggesting that the absence of mTOR should lead to embryonic lethality at an earlier stage. To resolve this discrepancy, we set out to disrupt the mTOR gene and analyze the outcome in both heterozygous and homozygous settings. Heterozygous mTOR (mTOR(+/-)) mice do not display any overt phenotype, although mouse embryonic fibroblasts derived from these mice show a 50% reduction in mTOR protein levels and phosphorylation of S6 kinase 1 T389, a site whose phosphorylation is directly mediated by mTOR. However, S6 phosphorylation, raptor levels, cell size, and cell cycle transit times are not diminished in these cells. In contrast to the situation in mTOR(+/-) mice, embryonic development of homozygous mTOR(-/-) mice appears to be arrested at E5.5; such embryos are severely runted and display an aberrant developmental phenotype. The ability of these embryos to implant corresponds to a limited level of trophoblast outgrowth in vitro, reflecting a maternal mRNA contribution, which has been shown to persist during preimplantation development. Moreover, mTOR(-/-) embryos display a lesion in inner cell mass proliferation, consistent with the inability to establish embryonic stem cells from mTOR(-/-) embryos. 相似文献
8.
Tenkanen M Kontkanen H Isoniemi R Spetz P Holmbom B 《Applied microbiology and biotechnology》2002,60(1-2):120-127
A well-known lipase, Lip 3 of Candida rugosa, was purified to homogeneity from a commercial lipase preparation, using hydrophobic interaction and anion exchange chromatography. Lip 3, which has been reported to act on cholesteryl esters, was also found to be active on plant-derived steryl esters. Lip 3 had optimal activity at pH 5-7 and below 55 degrees C. It was able to hydrolyse steryl esters totally in a clear micellar aqueous solution. However, the action on a dispersed colloidal steryl ester solution was limited and only about half of the steryl esters were degraded. The degree of hydrolysis was not improved by addition of fresh enzyme. The composition of released fatty acids and sterols was, however, almost identical to that obtained by alkaline hydrolysis, showing that all the different steryl esters were hydrolysed equally and that none of the individual components were responsible for incomplete hydrolysis. Thus, it appeared that the physical state of the colloidal steryl ester dispersion limited the action of Lip 3. Wood resins contain both triglycerides and steryl esters among the hydrophobic components, which create problems in papermaking. The simultaneous enzymatic hydrolysis of triglycerides and steryl ester is therefore of considerable interest and Lip 3 is the first enzyme reported to act on both triglycerides and steryl esters. 相似文献
9.
Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1 总被引:8,自引:1,他引:7
There are 10 gene families that have members on both human chromosome 6
(6p21.3, the location of the human major histocompatibility complex [MHC])
and human chromosome 9 (mostly 9q33-34). Six of these families also have
members on mouse chromosome 17 (the mouse MHC chromosome) and mouse
chromosome 2. In addition, four of these families have members on human
chromosome 1 (1q21-25 and 1p13), and two of these have members on mouse
chromosome 1. One hypothesis to explain these patterns is that members of
the 10 gene families of human chromosomes 6 and 9 were duplicated
simultaneously as a result of polyploidization or duplication of a
chromosome segment ("block duplication"). A subsequent block duplication
has been proposed to account for the presence of representatives of four of
these families on human chromosome 1. Phylogenetic analyses of the 9 gene
families for which data were available decisively rejected the hypothesis
of block duplication as an overall explanation of these patterns. Three to
five of the genes on human chromosomes 6 and 9 probably duplicated
simultaneously early in vertebrate history, prior to the divergence of
jawed and jawless vertebrates, and shortly after that, all four of the
genes on chromosomes 1 and 9 probably duplicated as a block. However, the
other genes duplicated at different times scattered over at least 1.6
billion years. Since the occurrence of these clusters of related genes
cannot be explained by block duplication, one alternative explanation is
that they cluster together because of shared functional characteristics
relating to expression patterns.
相似文献
10.
Evolutionary distances for protein-coding sequences: modeling site- specific residue frequencies 总被引:13,自引:8,他引:5
Estimation of evolutionary distances from coding sequences must take into
account protein-level selection to avoid relative underestimation of longer
evolutionary distances. Current modeling of selection via site-to-site rate
heterogeneity generally neglects another aspect of selection, namely
position-specific amino acid frequencies. These frequencies determine the
maximum dissimilarity expected for highly diverged but functionally and
structurally conserved sequences, and hence are crucial for estimating long
distances. We introduce a codon- level model of coding sequence evolution
in which position-specific amino acid frequencies are free parameters. In
our implementation, these are estimated from an alignment using methods
described previously. We use simulations to demonstrate the importance and
feasibility of modeling such behavior; our model produces linear distance
estimates over a wide range of distances, while several alternative models
underestimate long distances relative to short distances. Site-to-site
differences in rates, as well as synonymous/nonsynonymous and
first/second/third-codon-position differences, arise as a natural
consequence of the site-to-site differences in amino acid frequencies.
相似文献