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261.
The epidemic of Human Immunodeficiency Virus type 1 infection in Italy is mostly ascribed to the B subtype, which represents the prevalent subtype in Western Countries. The virus isolates of the B subtype, moreover, show an increasing nucleotide heterogeneity over time, indicating a continuous intra-subtype dynamic evolution, typical of long-lasting epidemics. In recent years, however, the progressive decrease in the transmission rate among the historically defined risk groups (i.e. homosexuals and IDUs) and the parallel increase in heterosexual transmission are slowly introducing variants of non-B subtype into the Italian HIV-1 epidemic. This appears to be strictly linked to the growing number of immigrants from non-Western Countries, where non-B clades and CRFs are prevalent, and consequent inter-racial blending. The distribution of these novel genetic forms needs to be evaluated by continuous molecular monitoring nationwide to verify whether they will overcome the pre-existing B-clade epidemic, which could have significant implications for diagnosis, treatment and vaccine development. Here we review the genetic evolution of HIV-1 spreading within the Italian epidemic. 相似文献
262.
Rawson PM Molette C Videtta M Altieri L Franceschini D Donato T Finocchi L Propato A Paroli M Meloni F Mastroianni CM d'Ettorre G Sidney J Sette A Barnaba V 《Nature medicine》2007,13(12):1431-1439
We found that the proteome of apoptotic T cells includes prominent fragments of cellular proteins generated by caspases and that a high proportion of distinct T cell epitopes in these fragments is recognized by CD8+ T cells during HIV infection. The frequencies of effector CD8+ T cells that are specific for apoptosis-dependent epitopes correlate with the frequency of circulating apoptotic CD4+ T cells in HIV-1-infected individuals. We propose that these self-reactive effector CD8+ T cells may contribute to the systemic immune activation during chronic HIV infection. The caspase-dependent cleavage of proteins associated with apoptotic cells has a key role in the induction of self-reactive CD8+ T cell responses, as the caspase-cleaved fragments are efficiently targeted to the processing machinery and are cross-presented by dendritic cells. These findings demonstrate a previously undescribed role for caspases in immunopathology. 相似文献
263.
Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state 总被引:2,自引:0,他引:2
Brown BD Gentner B Cantore A Colleoni S Amendola M Zingale A Baccarini A Lazzari G Galli C Naldini L 《Nature biotechnology》2007,25(12):1457-1467
We have shown previously that transgene expression can be suppressed in hematopoietic cells using vectors that are responsive to microRNA (miRNA) regulation. Here we investigate the potential of this approach for more sophisticated control of transgene expression. Analysis of the relationship between miRNA expression levels and target mRNA suppression suggested that suppression depends on a threshold miRNA concentration. Using this information, we generated vectors that rapidly adjust transgene expression in response to changes in miRNA expression. These vectors sharply segregated transgene expression between closely related states of therapeutically relevant cells, including dendritic cells, hematopoietic and embryonic stem cells, and their progeny, allowing positive/negative selection according to the cells' differentiation state. Moreover, two miRNA target sites were combined to restrict transgene expression to a specific cell type in the liver. Notably, the vectors did not detectably perturb endogenous miRNA expression or regulation of natural targets. The properties of miRNA-regulated vectors should allow for safer and more effective therapeutic applications. 相似文献
264.
D'Onofrio J Petraccone L Erra E Martino L Fabio GD Napoli LD Giancola C Montesarchio D 《Bioconjugate chemistry》2007,18(4):1194-1204
Oligodeoxyribonucleotides of sequence d(5'TGGGAG3') carrying bulky aromatic groups at the 5' end were found to exhibit potent anti-HIV activity [Hotoda, H., et al. (1998) J. Med. Chem. 41, 3655-3663 and references therein]. Structure-activity relationship investigations indicated that G-quadruplex formation, as well as the presence of large aromatic substituents at the 5'-end, were both essential for their antiviral activity. In this work, we synthesized some representative examples of the anti-HIV active Hotoda's 6-mers and analyzed the resulting G-quadruplexes by CD, DSC, and molecular modeling studies, in comparison with the unmodified oligonucleotide. In the case of the sequence carrying the 3,4-dibenzyloxybenzyl (DBB) group, identified as the best candidate for further drug optimization, we developed an alternative protocol to synthesize the 5'-DBB-thymidine phosphoramidite building block in higher yields. The thermodynamic and kinetic parameters for the association/dissociation processes of the 5'-conjugated quadruplexes, determined with respect to the unmodified one, were discussed in light of the molecular modeling studies. The aromatic groups at the 5' position of d(5'TGGGAG3') dramatically enhance both the equilibrium and the rate of formation of the quadruplex complexes. The overall stability of the investigated quadruplexes was found to correlate with the reported IC50 values, thus furnishing quantitative evidence for the hypothesis that the G-quadruplex structures are the ultimate active species, effectively responsible for the biological activity. 相似文献
265.
Baldari C Di Luigi L Silva SG Gallotta MC Emerenziani GP Pesce C Guidetti L 《Journal of strength and conditioning research / National Strength & Conditioning Association》2007,21(4):1160-1165
To investigate the relationships between race performance and parameters at the optimal power output for lactate removal, 10 male triathletes were examined. Exercise intensities for lactate removal were defined by calculating 50% of difference (DeltaT) between running velocity (V(r)) at individual anaerobic threshold (IAT) and at individual ventilatory threshold (IVT), then choosing 3 V(r): at IVT plus 50% DeltaT (IVT(+50%DeltaT)), at IVT, and at IVT minus 50% DeltaT (IVT(-50%DeltaT)). After a 6-minute treadmill run at 75% of difference between IAT and V(.-)O2max, all triathletes performed a 30-minute active recovery run at IVT(+50%DeltaT), IVT, and IVT(-50%DeltaT). Capillary blood lactate was determined at 1, 3, 6, 9, 12, 15, 20, 25, and 30 minutes of recovery. The IVT(-50%DeltaT) recovery was the most efficient V(r) for lactate removal. Running velocities at IVT and IVT(-50%DeltaT) were highly (p < 0.01) related to cycle, run, and overall race time. V(.-)O2max values at IAT, IVT(+50%DeltaT), and IVT were less (p < 0.05) related to split and overall race time. The variable most related to overall race time, as determined by stepwise multiple linear regression analysis, was the V(r) at IVT(-50%DeltaT) (r = 0.87, p = 0.001). The R(2) value of 0.76 indicated that V(r) at IVT(-50%DeltaT) could account for 76% of the variance in triathlon race time. This study shows that the race performances of triathletes are highly related to the V(r) at which the most efficient lactate removal (IVT(-50%DeltaT)) occurs. These findings suggest that the assessment of V(r) at IVT and IAT (from which V(r) at IVT(-50%DeltaT) are calculated) may be a useful method for monitoring training-induced adaptations and performance improvements in athletes who participate in Olympic triathlons. 相似文献
266.
Balbis E Patriarca S Furfaro AL Cottalasso D Pronzato MA Carlier P Botta F Marinari UM Fontana L Traverso N 《Redox report : communications in free radical research》2007,12(1):59-62
Results on oxidative markers during ageing are not consistent throughout the scientific literature; however, successful ageing may depend on better ability to cope with oxidative stress. A previous study of ours showed that successful ageing could actually be related to enhanced response to oxidatively modified proteins. In this study, a healthy nonagenarian population (OVER-90) was examined for various blood oxidative biomarkers and compared with a healthy population of blood donors (age range, 23-66 years). Blood glutathione, both total (tGSH) and oxidised (GSSG), and total plasmatic antioxidant status were maintained in the OVER-90 at a level similar to the control population. Sulphydryl (sulfhydryl) groups and glutathione peroxidase (GPx) were instead decreased. The results are discussed in a possible unifying view: the OVER-90 population could possess a globally preserved antioxidant ability, though some signs of oxidative damage are present and some structures could be 'sacrificed' in order to keep the redox equilibrium. 相似文献
267.
Bontempo P Mita L Miceli M Doto A Nebbioso A De Bellis F Conte M Minichiello A Manzo F Carafa V Basile A Rigano D Sorbo S Castaldo Cobianchi R Schiavone EM Ferrara F De Simone M Vietri M Cioffi M Sica V Bresciani F de Lera AR Altucci L Molinari AM 《The international journal of biochemistry & cell biology》2007,39(10):1902-1914
Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems. 相似文献
268.
Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance 总被引:4,自引:0,他引:4
269.
270.
Carlo Alviggi Alberto Revelli Paola Anserini Antonio Ranieri Luigi Fedele Ida Strina Marco Massobrio Nicola Ragni Giuseppe De Placido 《Reproductive biology and endocrinology : RB&E》2007,5(1):45-7