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131.
Temple CA George GN Hilton JC George MJ Prince RC Barber MJ Rajagopalan KV 《Biochemistry》2000,39(14):4046-4052
Conditions for heterologous expression of Rhodobacter sphaeroides biotin sulfoxide reductase in Escherichia coli were modified, resulting in a significant improvement in the yield of recombinant enzyme and enabling structural studies of the molybdenum center. Quantitation of the guanine and the molybdenum as compared to that found in R. sphaeroides DMSO reductase demonstrated the presence of the bis(MGD)molybdenum cofactor. UV-visible absorption spectra were obtained for the oxidized, NADPH-reduced, and dithionite-reduced enzyme. EPR spectra were obtained for the Mo(V) state of the enzyme. X-ray absorption spectroscopy at the molybdenum K-edge has been used to probe the molybdenum coordination of the enzyme. The molybdenum site of the oxidized protein possesses a Mo(VI) mono-oxo site (Mo=O at 1.70 A) with additional coordination by approximately four thiolate ligands at 2.41 A and probably one oxygen or nitrogen at 1.95 A. The NADPH- and dithionite-reduced Mo(IV) forms of the enzyme are des-oxo molybdenum sites with approximately four thiolates at 2.33 A and two different Mo-O/N ligands at 2.19 and 1.94 A. 相似文献
132.
Despite the potential for many possible secondary-structure conformations, the native sequence of ribosomal RNA (rRNA) is able to find the correct and universally conserved core fold. This study reports a computational analysis investigating two mechanisms that appear to constrain rRNA secondary-structure conformational space: ribosomal proteins and rRNA sequence composition. The analysis was carried out by using rRNA–ribosomal protein interaction data for the Escherichia coli 16S rRNA and free energy minimization software for secondary-structure prediction. The results indicate that selection pressures on rRNA sequence composition and ribosomal protein–rRNA interaction play a key role in constraining the rRNA secondary structure to a single stable form. 相似文献
133.
Kant SG van der Weij AM Oostdijk W Wit JM Robinson DO Temple IK Mackay DJ 《Human genetics》2005,117(4):398-401
Transient neonatal diabetes mellitus (TNDM) is associated with paternal over-expression of an imprinted locus on chromosome 6q24, which contains one differentially methylated region (DMR); maternal demethylation at the DMR accounts for ~20% of cases. Here we report female monozygous triplets, two of whom have TNDM arising from loss of maternal methylation within the TNDM DMR. 相似文献
134.
Neural progenitor cells can be derived from a variety of developmental stages when they are preferentially proliferating, undergoing neurogenesis or undergoing gliogenesis. We used FACS sorting and the LeX surface marker to enrich neural progenitor cells from different embryonic stages and adult and compared their gene expression profiles using Affymetrix Microarrays. Our results show that, while there are common genes expressed in the progenitor cell population from all stages, there are also significant differences in gene expression patterns that correlate with stage-related behaviors. These data indicate that progenitor cells change during development and that adult and embryonic neural progenitor cells are intrinsically different. 相似文献
135.
Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells 总被引:3,自引:0,他引:3
It has been debated whether asymmetric distribution of cell surface receptors during mitosis could generate asymmetric cell divisions by yielding daughters with different environmental responsiveness and, thus, different fates. We have found that in mouse embryonic forebrain ventricular and subventricular zones, the EGFR can distribute asymmetrically during mitosis in vivo and in vitro. This occurs during divisions yielding two Nestin+ progenitor cells, via an actin-dependent mechanism. The resulting sibling progenitor cells respond differently to EGFR ligand in terms of migration and proliferation. Moreover, they express different phenotypic markers: the EGFRhigh daughter usually has radial glial/astrocytic markers, while its EGFRlow sister lacks them, indicating fate divergence. Lineage trees of cultured cortical glioblasts reveal repeated EGFR asymmetric distribution, and asymmetric divisions underlie formation of oligodendrocytes and astrocytes in clones. These data suggest that asymmetric EGFR distribution contributes to forebrain development by creating progenitors with different proliferative, migratory, and differentiation responses to ligand. 相似文献
136.
Methamphetamine abuse has increased rapidly in the United States over the last few years. Besides socioeconomic hardships acquired from using the drug, there are several adverse medical outcomes. Although there have been many reports of cardiovascular and central nervous system toxicities, there are few case reports of bowel ischemia induced by the drug. We report an unusual case of methamphetamine-associated intestinal infarction. 相似文献
137.
Temple R 《Molecular interventions》2004,4(6):313-317
Robert Temple has spent more than thirty years of his career at the Food and Drug Administration-and he still likes it! After medical school, internship, and residency, Temple pursued endocrinology research at the NIH before deciding, in the early 70s, to apply his interests in science to consumer advocacy at the FDA. The FDA was undergoing enormous changes at that time, and Temple enjoyed the challenges associated with improving drug development and patient safety. Always relying on a critical evaluation of data, he is comfortable discussing mechanisms of drug action, experimental design, and regulatory policies, as well as the social implications of direct-to-consumer advertising of drugs. Currently, Temple is Director of one of the six Offices of Drug Evaluation and also serves as the Associate Director for Medical Policy. 相似文献
138.
Thomas N Plasterer Temple F Smith Scott C Mohr 《Genome biology》2001,2(6):research0021.1-research002116
Background
We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three-dimensional structures that aid in the interpretation of effects of missense mutations.Results
This survey reports such an analysis for 15 missense mutations, one insertion and three deletions involved in Leber's hereditary optic neuropathy, Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Mohr-Tranebjaerg syndrome, iron-storage disorders related to Friedreich's ataxia, and hereditary spastic paraplegia. We present structural correlations for seven of the mutations.Conclusions
Of the 19 mutations analyzed, 14 involved changes in very highly conserved parts of the affected proteins. Five out of seven structural correlations provided reasonable explanations for the malfunctions. As additional genetic and structural data become available, this methodology can be extended. It has the potential for assisting in identifying new disease-related genes. Furthermore, profiles with structural homologs can generate mechanistic hypotheses concerning the underlying biochemical processes - and why they break down as a result of the mutations. 相似文献139.
Nicole E. Bowen Joshua Temple Caitlin Shepard Adrian Oo Fidel Arizaga Priya Kapoor-Vazirani Mirjana Persaud Corey H. Yu Dong-Hyun Kim Raymond F. Schinazi Dmitri N. Ivanov Felipe Diaz-Griffero David S. Yu Yong Xiong Baek Kim 《The Journal of biological chemistry》2021,297(4)
Elevated intracellular levels of dNTPs have been shown to be a biochemical marker of cancer cells. Recently, a series of mutations in the multifunctional dNTP triphosphohydrolase (dNTPase), sterile alpha motif and histidine–aspartate domain–containing protein 1 (SAMHD1), have been reported in various cancers. Here, we investigated the structure and functions of SAMHD1 R366C/H mutants, found in colon cancer and leukemia. Unlike many other cancer-specific mutations, the SAMHD1 R366 mutations do not alter cellular protein levels of the enzyme. However, R366C/H mutant proteins exhibit a loss of dNTPase activity, and their X-ray structures demonstrate the absence of dGTP substrate in their active site, likely because of a loss of interaction with the γ-phosphate of the substrate. The R366C/H mutants failed to reduce intracellular dNTP levels and restrict HIV-1 replication, functions of SAMHD1 that are dependent on the ability of the enzyme to hydrolyze dNTPs. However, these mutants retain dNTPase-independent functions, including mediating dsDNA break repair, interacting with CtIP and cyclin A2, and suppressing innate immune responses. Finally, SAMHD1 degradation in human primary-activated/dividing CD4+ T cells further elevates cellular dNTP levels. This study suggests that the loss of SAMHD1 dNTPase activity induced by R366 mutations can mechanistically contribute to the elevated dNTP levels commonly found in cancer cells. 相似文献
140.
Temple Grandin 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2009,364(1522):1437-1442
My mind is similar to an Internet search engine that searches for photographs. I use language to narrate the photo-realistic pictures that pop up in my imagination. When I design equipment for the cattle industry, I can test run it in my imagination similar to a virtual reality computer program. All my thinking is associative and not linear. To form concepts, I sort pictures into categories similar to computer files. To form the concept of orange, I see many different orange objects, such as oranges, pumpkins, orange juice and marmalade. I have observed that there are three different specialized autistic/Asperger cognitive types. They are: (i) visual thinkers such as I who are often poor at algebra, (ii) pattern thinkers such as Daniel Tammet who excel in math and music but may have problems with reading or writing composition, and (iii) verbal specialists who are good at talking and writing but they lack visual skills. 相似文献