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31.
Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans 总被引:10,自引:3,他引:10
Recent studies of mitochondrial DNA (mtDNA) variation in mammals and
Drosophila have shown an excess of amino acid variation within species
(replacement polymorphism) relative to the number of silent and replacement
differences fixed between species. To examine further this pattern of
nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5
genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans.
Of interest are the frequency spectra of silent and replacement
polymorphisms, and potential variation among genes and taxa in the
departures from neutral expectations. The Drosophila ND3 and ND5 data show
no significant excess of replacement polymorphism using the
McDonald-Kreitman test. These data are in contrast to significant
departures from neutrality for the ND3 gene in mammals and other genes in
Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however,
both Drosophila and human mtDNA show very significant excesses of amino
acid polymorphism. Silent polymorphisms at ND5 show a significantly higher
variance in frequency than replacement polymorphisms, and the latter show a
significant skew toward low frequencies (Tajima's D = -1.954). These
patterns are interpreted in light of the nearly neutral theory where mildly
deleterious amino acid haplotypes are observed as ephemeral variants within
species but do not contribute to divergence. The patterns of polymorphism
and divergence at charge-altering amino acid sites are presented for the
Drosophila ND5 gene to examine the evolution of functionally distinct
mutations. Excess charge-altering polymorphism is observed at the carboxyl
terminal and excess charge-altering divergence is detected at the amino
terminal. While the mildly deleterious model fits as a net effect in the
evolution of nonrecombining mitochondrial genomes, these data suggest that
opposing evolutionary pressures may act on different regions of
mitochondrial genes and genomes.
相似文献
32.
Jeffrey W. Perry Mohammad Ahmed Kyeong-Ok Chang Nicholas J. Donato Hollis D. Showalter Christiane E. Wobus 《PLoS pathogens》2012,8(7)
Ubiquitin (Ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. As obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (Ub) cycle to their advantage by encoding Ub-modifying proteins including deubiquitinases (DUBs). However, how cellular DUBs modulate specific viral infections, such as norovirus, is poorly understood. To examine the role of DUBs during norovirus infection, we used WP1130, a small molecule inhibitor of a subset of cellular DUBs. Replication of murine norovirus in murine macrophages and the human norovirus Norwalk virus in a replicon system were significantly inhibited by WP1130. Chemical proteomics identified the cellular DUB USP14 as a target of WP1130 in murine macrophages, and pharmacologic inhibition or siRNA-mediated knockdown of USP14 inhibited murine norovirus infection. USP14 is a proteasome-associated DUB that also binds to inositol-requiring enzyme 1 (IRE1), a critical mediator of the unfolded protein response (UPR). WP1130 treatment of murine macrophages did not alter proteasome activity but activated the X-box binding protein-1 (XBP-1) through an IRE1-dependent mechanism. In addition, WP1130 treatment or induction of the UPR also reduced infection of other RNA viruses including encephalomyocarditis virus, Sindbis virus, and La Crosse virus but not vesicular stomatitis virus. Pharmacologic inhibition of the IRE1 endonuclease activity partially rescued the antiviral effect of WP1130. Taken together, our studies support a model whereby induction of the UPR through cellular DUB inhibition blocks specific viral infections, and suggest that cellular DUBs and the UPR represent novel targets for future development of broad spectrum antiviral therapies. 相似文献
33.
Parmeggiani F Gemmati D Costagliola C Semeraro F Perri P D'Angelo S Romano MR De Nadai K Sebastiani A Incorvaia C 《Molecular diagnosis & therapy》2011,15(4):195-210
In Western countries, therapeutic management of patients affected by choroidal neovascularization (CNV) secondary to different typologies of macular degeneration represents a major health care problem. Age-related macular degeneration is the disease most frequently associated with CNV development. Schematically, CNVs can be distinguished into classic and occult subtypes, which are characterized by variable natural history and different responsiveness to some therapeutic procedures. At present, the dramatic vision loss due to CNV can be mainly treated by two interventional strategies, which are utilizable in either single or combined modalities: photodynamic therapy with verteporfin (PDT-V), and intravitreal administration of drugs acting against vascular endothelial growth factor. The combined use of PDT-V and anti-angiogenic drugs represents one of the most promising strategies against neovascular macular degeneration, but it unavoidably results in an expensive increase in health resource utilization. However, the positive data from several studies serve as a basis for reconsidering the role of PDT-V, which has undergone a renaissance prompted by the need for a more rational therapeutic approach toward CNV. New pharmacogenetic knowledge of PDT-V points to exploratory prospects to optimize the clinical application of this intriguing photothrombotic procedure. In fact, a Medline search provides data regarding the role of several single nucleotide polymorphisms (SNPs) as genetic predictors of CNV responsiveness to PDT-V. Specifically, correlations between SNPs and different levels of PDT-V efficacy have been detected by examining the gene variants influencing (i) thrombo-coagulative pathways, i.e. methylenetetrahydrofolate reductase (MTHFR) 677C>T (rs1801133), factor V (F5) 1691G>A (rs6025), prothrombin (F2) 20210G>A (rs1799963), and factor XIII-A (F13A1) 185G>T (rs5985); (ii) complement activation and/or inflammatory processes, i.e. complement factor H (CFH) 1277T>C (rs1061170), high-temperature requirement factor A1 (HTRA1) promoter -512G>A (rs11200638), and two variants of the C-reactive protein (CRP) gene (rs2808635 and rs876538); and (iii) production and bioavailability of vascular endothelial growth factor (VEGFA -2578C>A [rs699947] and rs2146323). This article critically evaluates both the clinical plausibility and the opportunity to utilize the most important SNP-response interactions of PDT-V for an effective upgrade of the current anti-CNV therapeutic scenario. In addition, the pharmacogenetics of a very severe post-PDT-V adverse event, i.e. a decrease in acute vision, is briefly discussed. A comprehensive appraisal of the findings reviewed in this article should be carefully considered to design future trials aimed at verifying (after proper genotypic stratification of the enrolled patients) whether these innovative pharmacogenetic approaches will be able to improve the multifaceted interventional management of neovascular macular degeneration. 相似文献
34.
Notomista E Pennacchio F Cafaro V Smaldone G Izzo V Troncone L Varcamonti M Di Donato A 《Microbial ecology》2011,61(3):582-594
Novosphingobium sp. PP1Y, isolated from a surface seawater sample collected from a closed bay in the harbour of Pozzuoli (Naples, Italy),
uses fuels as its sole carbon and energy source. Like some other Sphingomonads, this strain can grow as either planktonic
free cells or sessile-aggregated flocks. In addition, this strain was found to grow as biofilm on several types of solid and
liquid hydrophobic surfaces including polystyrene, polypropylene and diesel oil. Strain PP1Y is not able to grow on pure alkanes
or alkane mixtures but is able to grow on a surprisingly wide range of aromatic compounds including mono, bi, tri and tetracyclic
aromatic hydrocarbons and heterocyclic compounds. During growth on diesel oil, the organic layer is emulsified resulting in
the formation of small biofilm-coated drops, whereas during growth on aromatic hydrocarbons dissolved in paraffin the oil
layer is emulsified but the drops are coated only if the mixtures contain selected aromatic compounds, like pyrene, propylbenzene,
tetrahydronaphthalene and heterocyclic compounds. These peculiar characteristics suggest strain PP1Y has adapted to efficiently
grow at the water/fuel interface using the aromatic fraction of fuels as the sole carbon and energy source. 相似文献
35.
36.
A revision of the monoraphid pennate diatom genus Campyloneis Grunow was carried out based on LM and EM observations. The material examined originated from various herbarium collections and from extant epiphytic diatom communities on leaves of Posidonia spp. We also examined the generitype C. grevillei (Smith) Grunow and the fossil material of C. gheyselinchi Reinhold from which the author extracted the type. Our results clarified the fine structure of C. grevillei and C. gheyselinchi. Of the various varieties of C. grevillei, only the variety argus (Grunow) Cleve was retained. This differs from the nominate variety in the arrangement and shape of the areolae adjacent to the sternum of the araphid valve. The newly described taxon Campyloneis juliae De Stefano differs from all Campyloneis species in areolae ultrastructure and morphology of the valvocopulae. As for the fossil species C. gheyselinchi, the sternum valve areolae are similar to those of C. grevillei, but scarcity of frustules in the type material prohibited evaluation of its variability. For this reason we provisionally maintained its rank of species. The elaborate linking systems among the valvocopulae and valves in Campyloneis species appear to provide structural reinforcement against pressure from neighboring epiphytic diatoms and scouring of seagrass leaves. 相似文献
37.
Nataliya Di Donato Ying Y. Jean A. Murat Maga Briana D. Krewson Alison B. Shupp Maria I. Avrutsky Achira Roy Sarah Collins Carissa Olds Rebecca A. Willert Agnieszka M. Czaja Rachel Johnson Jessi A. Stover Steven Gottlieb Deborah Bartholdi Anita Rauch Amy Goldstein Victoria Boyd-Kyle Kimberly A. Aldinger Ghayda M. Mirzaa Anke Nissen Karlla W. Brigatti Erik G. Puffenberger Kathleen J. Millen Kevin A. Strauss William B. Dobyns Carol M. Troy Robert N. Jinks 《American journal of human genetics》2016,99(5):1117-1129
38.
8-Hydroxydeoxyguanosine (8-OHdG) has been widely used as a biomarker of oxidative DNA damage in both animal and human studies. However, controversial data exist on the relationship between 8-OHdG formation and age, sex and tobacco smoking in humans, while few or no data are available on other exposures such as environmental tobacco smoke, alcohol, coffee and tea consumption. We investigated the level of 8-OHdG in DNA from peripheral leukocytes among 102 healthy adults living in Brescia province, North Italy, aged 25-45 (mean: 35.2 years), of which 51 were males. 8-OHdG levels expressed as a ratio to total deoxyguanosine (8-OHdG/106 dG) in DNA showed wide interindividual variation, the highest value (63.8) being 6. 2-fold greater than the lowest (10.3). Current smokers showed lower mean 8-OHdG values than subjects who never smoked (29.3 and 34.0, respectively, p<0.05), and an inverse relationship was found between 8-OHdG and lifetime smoking, which was independent of age, sex and body mass index. An inverse relationship was also found with coffee drinking while no association was observed with alcohol and tea consumption, exposure to environmental tobacco smoke and use of vitamins in all subjects, and with use of oral contraceptives in females. The inverse relationship between smoking status and 8-OHdG levels could be explained by the presence of efficient repair processes for the oxidative damage induced by smoking. In this study, the smokers were relatively young (77% were less than 40 years) and only 7% smoked 30 or more cigarettes a day. In conclusion, it would appear that 8-OHdG levels in leukocytes may not provide a sensitive marker of exposure to tobacco smoking. 相似文献
39.
40.
Eva Pericolini Elena Gabrielli Giovanni Bistoni Elio Cenci Stefano Perito Siu-Kei Chow Francesca Riuzzi Rosario Donato Arturo Casadevall Anna Vecchiarelli 《PloS one》2010,5(9)
Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45−/− cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45−/− cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis. 相似文献