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The focus of experiments presented in this dissertation is to determine how signals created by exposure to environmental stimuli are integrated at the level of transcription, resulting in the generation of specific patterns of gene expression. The model system used was expression of the neurotensinl neuromedin N (NT/N) neuropeptide gene in the neuroendocrine PC12 cell line. This gene is synergistically activated in PC12 cells in response to nerve growth factor, lithium, glucocorticoids, and activators of adenylate cyclase. Several cis-regulatory elements were identified within a 200 bp regulatory region, including AP-1, CRE, and GRE-like elements. Mutational analysis confirmed the importance of these elements for responses to inducer combinations. The primary objective was to identify proteins that interact with NT/N promoter sequences and determine if they are important in mediating responses to inducer combinations. The first set of experiments was designed to investigate changes in AP-1 binding
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*  Can dicyclomine be used daily to prevent stomach cramps?

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*  Recall Roundup: October 13, 2009

Stolen Tylenol Alert: McNeil Consumer Healthcare, Division of McNEIL-PPC, Inc., is working with the U.S. Food and Drug Administration, Office of Criminal Investigations (FDA), and other law enforcement officials to recover cases of select lots of TYLENOL® Arthritis and TYLENOL® PM products that were stolen from a cargo terminal at the Jacksonville Port Authority in Jacksonville, Florida on September 25, 2009 ...
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*  Dianqing Sun, PhD

R. E. Lee, J. G. Hurdle, J. Liu, D. F. Bruhn, T. Matt, M. S. Scherman, P. K. Vaddady, Z. Zheng, J. Qi, R. Akbergenov, S. Das, D. B. Madhura, C. Rathi, A. Trivedi, C. Villellas, R. B. Lee, Rakesh, S. L. Waidyarachchi, D.Sun, M. R. McNeil, J. A. Ainsa, H. I. Boshoff, M. Gonzalez-Juarrero, B. Meibohm, E. C. Böttger, A. J. Lenaerts, (2014). Spectinamides: A new class of semisynthetic anti-tuberculosis agents that overcome native drug efflux, Nat Med, 20(2), 152-158 ...
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*  What We Can Do for Our Country

The Tufts Journal, the university's online newspaper of record, is published twice-monthly during the academic year, and monthly otherwise, by the Tufts University Office of Publications. Editorial offices are located at 80 George St., Medford, MA 02155. Telephone: 617-627-4503; fax: (617) 627-3549; e-mail: taylor.mcneil@tufts.edu
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*  Caldecott Award Selection Committee - 2018 | Association for Library Service to Children (ALSC)

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*  Content about Analgesics - Drug Store News

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No data available that match "DNA, Mitochondrial"



(1/8708) Reticulate evolution and the origins of ribosomal internal transcribed spacer diversity in apomictic Meloidogyne.

Among root knot nematodes of the genus Meloidogyne, the polyploid obligate mitotic parthenogens M. arenaria, M. javanica, and M. incognita are widespread and common agricultural pests. Although these named forms are distinguishable by closely related mitochondrial DNA (mtDNA) haplotypes, detailed sequence analyses of internal transcribed spacers (ITSs) of nuclear ribosomal genes reveal extremely high diversity, even within individual nematodes. This ITS diversity is broadly structured into two very different groups that are 12%-18% divergent: one with low diversity (< 1.0%) and one with high diversity (6%-7%). In both of these groups, identical sequences can be found within individual nematodes of different mtDNA haplotypes (i.e., among species). Analysis of genetic variance indicates that more than 90% of ITS diversity can be found within an individual nematode, with small but statistically significant (5%-10%; P < 0.05) variance distributed among mtDNA lineages. The evolutionarily distinct parthenogen M. hapla shows a similar pattern of ITS diversity, with two divergent groups of ITSs within each individual. In contrast, two diploid amphimictic species have only one lineage of ITSs with low diversity (< 0.2%). The presence of divergent lineages of rDNA in the apomictic taxa is unlikely to be due to differences among pseudogenes. Instead, we suggest that the diversity of ITSs in M. arenaria, M. javanica, and M. incognita is due to hybrid origins from closely related females (as inferred from mtDNA) and combinations of more diverse paternal lineages.  (+info)

(2/8708) Interaction of process partitions in phylogenetic analysis: an example from the swallowtail butterfly genus Papilio.

In this study, we explored how the concept of the process partition may be applied to phylogenetic analysis. Sequence data were gathered from 23 species and subspecies of the swallowtail butterfly genus Papilio, as well as from two outgroup species from the genera Eurytides and Pachliopta. Sequence data consisted of 1,010 bp of the nuclear protein-coding gene elongation factor-1 alpha (EF-1 alpha) as well as the entire sequences (a total of 2,211 bp) of the mitochondrial protein-coding genes cytochrome oxidase I and cytochrome oxidase II (COI and COII). In order to examine the interaction between the nuclear and mitochondrial partitions in a combined analysis, we used a method of visualizing branch support as a function of partition weight ratios. We demonstrated how this method may be used to diagnose error at different levels of a tree in a combined maximum-parsimony analysis. Further, we assessed patterns of evolution within and between subsets of the data by implementing a multipartition maximum-likelihood model to estimate evolutionary parameters for various putative process partitions. COI third positions have an estimated average substitution rate more than 15 times that of EF-1 alpha, while COII third positions have an estimated average substitution rate more than 22 times that of EF-1 alpha. Ultimately, we found that although the mitochondrial and nuclear data were not significantly incongruent, homoplasy in the fast-evolving mitochondrial data confounded the resolution of basal relationships in the combined unweighted parsimony analysis despite the fact that there was relatively strong support for the relationships in the nuclear data. We conclude that there may be shortcomings to the methods of "total evidence" and "conditional combination" because they may fail to detect or accommodate the type of confounding bias we found in our data.  (+info)

(3/8708) Evolutionary dynamics of a mitochondrial rearrangement "hot spot" in the Hymenoptera.

The arrangement of tRNA genes at the junction of the cytochrome oxidase II and ATPase 8 genes was examined across a broad range of Hymenoptera. Seven distinct arrangements of tRNA genes were identified among a group of wasps that have diverged over the last 180 Myr (suborder Apocrita); many of the rearrangements represent evolutionarily independent events. Approximately equal proportions of local rearrangements, inversions, and translocations were observed, in contrast to vertebrate mitochondria, in which local rearrangements predominate. Surprisingly, homoplasy was evident among certain types of rearrangement; a reversal of the plesiomorphic gene order has arisen on three separate occasions in the Insecta, while the tRNA(H) gene has been translocated to this locus on two separate occasions. Phylogenetic analysis indicates that this gene translocation is real and is not an artifactual translocation resulting from the duplication of a resident tRNA gene followed by mutation of the anticodon. The nature of the intergenic sequences surrounding this region does not indicate that it should be especially prone to rearrangement; it does not generally have the tandem or inverted repeats that might facilitate this plasticity. Intriguingly, these findings are consistent with the view that during the evolution of the Hymenoptera, rearrangements increased at the same time that the rate of point mutations and compositional bias also increased. This association may direct investigations into mitochondrial genome plasticity in other invertebrate lineages.  (+info)

(4/8708) Mitochondrial gene expression is regulated at the level of transcription during early embryogenesis of Xenopus laevis.

Mitochondrial transcription in the early Xenopus laevis embryo resumes several hours before active mtDNA replication, effectively decoupling mtDNA transcription and replication. This developmental feature makes Xenopus embryogenesis an appealing model system to investigate the regulation of mitochondrial transcription. Studies reported here refine our understanding of the timing, magnitude, and mechanism of this transcriptional induction event. Northern analyses of six mitochondrial mRNAs (normalized to mtDNA) reveal that transcript levels remain basal between fertilization and gastrulation and then undergo a coordinate induction, culminating in a 20-28-fold increase over egg levels by 48 h of development. Measurement of mitochondrial run-on transcription rates demonstrates a good correlation between transcription rates and transcript levels, showing that transcription itself is the primary determinant of transcript abundance. Experimental increases in mitochondrial ATP and energy charge also correlate with patterns of transcript levels and transcription rates, suggesting that developmental changes in the biochemical composition of the mitochondrial matrix could be regulating transcriptional activity. Consistent with this idea, transcriptional run-on rates in mitochondria of early embryos can be stimulated by the addition of tricarboxylic acid cycle intermediates to the run-on reaction. However, mitochondria of later stages do not show this response to the addition of metabolite. In combination, these data suggest that mitochondrial transcription is under metabolic regulation during early Xenopus embryogenesis.  (+info)

(5/8708) The yeast dynamin-like protein, Mgm1p, functions on the mitochondrial outer membrane to mediate mitochondrial inheritance.

The mdm17 mutation causes temperature-dependent defects in mitochondrial inheritance, mitochondrial morphology, and the maintenance of mitochondrial DNA in the yeast Saccharomyces cerevisiae. Defects in mitochondrial transmission to daughter buds and changes in mitochondrial morphology were apparent within 30 min after shifting cells to 37 degrees C, while loss of the mitochondrial genome occurred after 4-24 h at the elevated temperature. The mdm17 lesion mapped to MGM1, a gene encoding a dynamin-like GTPase previously implicated in mitochondrial genome maintenance, and the cloned MGM1 gene complements all of the mdm17 mutant phenotypes. Cells with an mgm1-null mutation displayed aberrant mitochondrial inheritance and morphology. A version of mgm1 mutated in a conserved residue in the putative GTP-binding site was unable to complement any of the mutant defects. It also caused aberrant mitochondrial distribution and morphology when expressed at high levels in cells that also contained a wild-type copy of the gene. Mgm1p was localized to the mitochondrial outer membrane and fractionated as a component of a high molecular weight complex. These results indicate that Mgm1p is a mitochondrial inheritance and morphology component that functions on the mitochondrial surface.  (+info)

(6/8708) Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer's disease.

To determine whether pathogenic mutations in mtDNA are involved in phenotypic expression of Alzheimer's disease (AD), the transfer of mtDNA from elderly patients with AD into mtDNA-less (rho0) HeLa cells was carried out by fusion of platelets or synaptosomal fractions of autopsied brain tissues with rho0 HeLa cells. The results showed that mtDNA in postmortem brain tissue survives for a long time without degradation and could be rescued in rho0 HeLa cells. Next, the cybrid clones repopulated with exogenously imported mtDNA from patients with AD were used for examination of respiratory enzyme activity and transfer of mtDNA with the pathogenic mutations that induce mitochondrial dysfunction. The presence of the mutated mtDNA was restricted to brain tissues and their cybrid clones that formed with synaptosomes as mtDNA donors, whereas no cybrid clones that isolated with platelets as mtDNA donors had detectable mutated mtDNA. However, biochemical analyses showed that all cybrid clones with mtDNA imported from platelets or brain tissues of patients with AD restored mitochondrial respiration activity to almost the same levels as those of cybrid clones with mtDNA from age-matched normal controls, suggesting functional integrity of mtDNA in both platelets and brain tissues of elderly patients with AD. These observations warrant the reassessment of the conventional concept that the accumulation of pathogenic mutations in mtDNA throughout the aging process is responsible for the decrease of mitochondrial respiration capacity with age and with the development of age-associated neurodegenerative diseases.  (+info)

(7/8708) Molecular studies suggest that cartilaginous fishes have a terminal position in the piscine tree.

The Chondrichthyes (cartilaginous fishes) are commonly accepted as being sister group to the other extant Gnathostomata (jawed vertebrates). To clarify gnathostome relationships and to aid in resolving and dating the major piscine divergences, we have sequenced the complete mtDNA of the starry skate and have included it in phylogenetic analysis along with three squalomorph chondrichthyans-the common dogfish, the spiny dogfish, and the star spotted dogfish-and a number of bony fishes and amniotes. The direction of evolution within the gnathostome tree was established by rooting it with the most closely related non-gnathostome outgroup, the sea lamprey, as well as with some more distantly related taxa. The analyses placed the chondrichthyans in a terminal position in the piscine tree. These findings, which also suggest that the origin of the amniote lineage is older than the age of the oldest extant bony fishes (the lungfishes), challenge the evolutionary direction of several morphological characters that have been used in reconstructing gnathostome relationships. Applying as a calibration point the age of the oldest lungfish fossils, 400 million years, the molecular estimate placed the squalomorph/batomorph divergence at approximately 190 million years before present. This dating is consistent with the occurrence of the earliest batomorph (skates and rays) fossils in the paleontological record. The split between gnathostome fishes and the amniote lineage was dated at approximately 420 million years before present.  (+info)

(8/8708) Coexistence of mitochondrial DNA and beta myosin heavy chain mutations in hypertrophic cardiomyopathy with late congestive heart failure.

OBJECTIVE: To investigate the possible coexistence of mitochondrial DNA (mtDNA) mutations in patients with beta myosin heavy chain (beta MHC) linked hypertrophic cardiomyopathy (HCM) who develop congestive heart failure. DESIGN: Molecular analysis of beta MHC and mtDNA gene defects in patients with HCM. SETTING: Cardiovascular molecular diagnostic and heart transplantation reference centre in north Italy. PATIENTS: Four patients with HCM who underwent heart transplantation for end stage heart failure, and after pedigree analysis of 60 relatives, eight additional affected patients and 27 unaffected relatives. A total of 111 unrelated healthy adult volunteers served as controls. Disease controls included an additional 27 patients with HCM and 102 with dilated cardiomyopathy. INTERVENTION: Molecular analysis of DNA from myocardial and skeletal muscle tissue and from peripheral blood specimens. MAIN OUTCOME MEASURES: Screening for mutations in beta MHC (exons 3-23) and mtDNA tRNA (n = 22) genes with denaturing gradient gel electrophoresis or single strand conformational polymorphism followed by automated DNA sequencing. RESULTS: One proband (kindred A) (plus seven affected relatives) had arginine 249 glutamine (Arg249Gln) beta MHC and heteroplasmic mtDNA tRNAIle A4300G mutations. Another unrelated patient (kindred B) with sporadic HCM had identical mutations. The remaining two patients (kindred C), a mother and son, had a novel beta MHC mutation (lysine 450 glutamic acid) (Lys450Glu) and a heteroplasmic missense (T9957C, phenylalanine (Phe)-->leucine (Leu)) mtDNA mutation in subunit III of the cytochrome C oxidase gene. The amount of mutant mtDNA was higher in the myocardium than in skeletal muscle or peripheral blood and in affected patients than in asymptomatic relatives. Mutations were absent in the controls. Pathological and biochemical characteristics of patients with mutations Arg249Gln plus A4300G (kindreds A and B) were identical, but different from those of the two patients with Lys450Glu plus T9957C(Phe-->Leu) mutations (kindred C). Cytochrome C oxidase activity and histoenzymatic staining were severely decreased in the two patients in kindreds A and B, but were unaffected in the two in kindred C. CONCLUSIONS: beta MHC gene and mtDNA mutations may coexist in patients with HCM and end stage congestive heart failure. Although beta MHC gene mutations seem to be the true determinants of HCM, both mtDNA mutations in these patients have known prerequisites for pathogenicity. Coexistence of other genetic abnormalities in beta MHC linked HCM, such as mtDNA mutations, may contribute to variable phenotypic expression and explain the heterogeneous behaviour of HCM.  (+info)



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