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1.
A family of mammalian Na+-dependent L-ascorbic acid transporters. 总被引:10,自引:0,他引:10
H Tsukaguchi T Tokui B Mackenzie U V Berger X Z Chen Y Wang R F Brubaker M A Hediger 《Nature》1999,399(6731):70-75
Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs. 相似文献
2.
Relationship between mitosis and the ordered structure of the stratum corneum in mouse epidermis 总被引:1,自引:0,他引:1
I C Mackenzie 《Nature》1970,226(5246):653-655
3.
Elimination of ribosomes during meiotic prophase 总被引:3,自引:0,他引:3
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O'Roak BJ Deriziotis P Lee C Vives L Schwartz JJ Girirajan S Karakoc E Mackenzie AP Ng SB Baker C Rieder MJ Nickerson DA Bernier R Fisher SE Shendure J Eichler EE 《Nature genetics》2011,43(6):585-589
Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs. 相似文献
6.
Tom Flanagan Janet McIntyre-Mills Tony Made Kelly Mackenzie Charles Morse Gayle Underwood Ken Bausch 《Systemic Practice and Action Research》2012,25(2):171-193
Sustainability is not simply about changing practices but more centrally about agreeing to change practices together. To achieve
such an end, groups need to improve processes for making complex decisions together. An online course was designed and tested
linking students in the United States and in Australia. Students engaged in a re-enactment of deliberations based on Hasan
Ozbekhan’s “Predicament of Mankind,” which was constructed originally under assignment from the founders of the Club of Rome
in 1970. This re-enactment included contemporary research for examples of a set of 49 continuous critical problems of mankind,
asynchronous clarification of these problems using a wiki, pair-wise construction of a systems view of problems assessed to
be of highest priority by the class, narrative analysis of the structure, and creative suggestions for resolving the systems
problem based on resources available today. This report comments on the strengths and challenges identified in an initial
application of an approach for building collaborative and systems thinking skills through an online course in a general education
curriculum. Findings are particularly meaningful for contemporary policy makers as well as online educators. 相似文献
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Baker M Mackenzie IR Pickering-Brown SM Gass J Rademakers R Lindholm C Snowden J Adamson J Sadovnick AD Rollinson S Cannon A Dwosh E Neary D Melquist S Richardson A Dickson D Berger Z Eriksen J Robinson T Zehr C Dickey CA Crook R McGowan E Mann D Boeve B Feldman H Hutton M 《Nature》2006,442(7105):916-919
Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival. 相似文献
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Ordered structure of the stratum corneum of mammalian skin 总被引:4,自引:0,他引:4
J C Mackenzie 《Nature》1969,222(5196):881-882