Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Q: Pandemic strains of HIV-1 (group M) encode a total of nine structural (gag, pol, env), regulatory (rev, tat) and accessory (vif, vpr, vpu, nef) genes. However, some subtype A and C viruses exhibit an unusual gene arrangement in which the first exon of rev (rev1) and the vpu gene are placed in the same open reading frame. Although this rev1-vpu gene fusion is present in a considerable fraction of HIV-1 strains, its functional significance is unknown.', 'Examining infectious molecular clones (IMCs) of HIV-1 that encode the rev1-vpu polymorphism, we show that a fusion protein is expressed in infected cells. Due to the splicing pattern of viral mRNA, however, these same IMCs also express a regular Vpu protein, which is produced at much higher levels. To investigate the function of the fusion gene, we characterized isogenic IMC pairs differing only in their ability to express a Rev1-Vpu protein. Analysis in transfected HEK293T and infected CD4+ T cells showed that all of these viruses were equally active in known Vpu functions, such as down-modulation of CD4 or counteraction of tetherin. Furthermore, the polymorphism did not affect Vpu-mediated inhibition of NF-кB activation or Rev-dependent nuclear export of incompletely spliced viral mRNAs. There was also no evidence for enhanced replication of Rev1-Vpu expressing viruses in primary PBMCs or ex vivo infected human lymphoid tissues. Finally, the frequency of HIV-1 quasispecies members that encoded a rev1-vpu fusion gene did not change in HIV-1 infected individuals over time.

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Q: Methionine sulfoxide reduction is an important protein repair pathway that protects against oxidative stress, controls protein function and has a role in regulation of aging. There are two enzymes that reduce stereospecifically oxidized methionine residues: MsrA (methionine-S-sulfoxide reductase) and MsrB (methionine-R-sulfoxide reductase). In many organisms, these enzymes are targeted to various cellular compartments. In mammals, a single MsrA gene is known, however, its product is present in cytosol, nucleus, and mitochondria. In contrast, three mammalian MsrB genes have been identified whose products are located in different cellular compartments.', 'In the present study, we identified and characterized alternatively spliced forms of mammalian MsrA. In addition to the previously known variant containing an N-terminal mitochondrial signal peptide and distributed between mitochondria and cytosol, a second mouse and human form was detected in silico. This form, MsrA(S), was generated using an alternative first exon. MsrA(S) was enzymatically active and was present in cytosol and nucleus in transfected cells, but occurred below detection limits in tested mouse tissues. The third alternative form lacked the active site and could not be functional. In addition, we found that mitochondrial and cytosolic forms of both MsrA and MsrB in Drosophila could be generated by alternative first exon splicing.

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Q: Peripheral arterial disease (PAD) is common among patients on chronic dialysis. Despite severe clinical manifestations, the indication for bypass surgery is controversial, because of the high morbidity and mortality rate of these patients. The less invasive percutaneous transluminal angioplasty (PTA) is a possible alternative, but data about PTA in dialysis patients are scarce.', 'We followed 107 dialysis patients (mean age 67+/-10, 75 males) with 132 ischaemic limbs (97% with critical limb ischaemia and ischaemic foot lesions or rest pain) consecutively treated by PTA.', 'PTA was successful in 97% of cases. Median follow-up was 22 months. Cumulative limb salvage rates at 12, 24, 36 and 48 months were 86, 84, 84 and 62%, respectively. Log-rank test showed an association between major amputation and baseline presence of foot lesions (P=0.04). This association was confirmed by a Cox survival multivariate analysis [hazard ratio (HR)=7.03, 95% confidence interval (CI)=1.1-43.0, P=0.035]. Limb salvage without any new intervention on the same leg was achieved in 70% of the cases, and was associated with the absence of diabetes mellitus (P=0.01), lower number of treated lesions (P=0.04) and proximal level (iliac and/or femoro-popliteal) of PTA (P<0.001). Independent predictors were diabetes mellitus (HR=3.47, 95% CI=1.31-9.17, P=0.01) and proximal PTA (HR=0.28, 95% CI=0.08-0.94, P=0.04). Fifty-three (49%) patients died during follow-up. Patients older than 67 years (the median value in our sample) had a 2.4-fold increase in mortality risk (95% CI=1.4-4.1, P<0.001).

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0
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