Early Gag Immunodominance of the HIV-Specific T-Cell Response during Acute/Early Infection Is Associated with Higher CD8+ T-Cell Antiviral Activity and Correlates with Preservation of the CD4+ T-Cell Compartment

The important role of the CD8⁺ T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8⁺ T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8⁺ T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4⁺ T-cell set points were observed in PHI subjects with higher HIV-specific CD8⁺ T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8⁺ T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.     

CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women

Background

The current concept of overweight/obesity is most likely related to a combination of increased caloric intake and decreased energy expenditure. Widespread inflammation, associated with both conditions, appears to contribute to the development of some obesity-related comorbidities. Interventions that directly or indirectly target individuals at high risk of developing obesity have been largely proposed because of the increasing number of overweight/obese cases worldwide. The aim of the present study was to assess CXCL16, IL-17, and BMP-2 plasma factors in middle-aged and elderly women and relate them to an overweight or obese status. In total, 117 women were selected and grouped as eutrophic, overweight, and obese, according to anthropometric parameters. Analyses of anthropometric and circulating biochemical parameters were followed by plasma immunoassays for CXCL-16, IL-17, and BMP-2.

Results

Plasma mediators increased in all overweight and obese individuals, with the exception of BMP-2 in the elderly group, whereas CXCL16 levels were shown to differentiate overweight and obese individuals. Overweight and/or obese middle-aged and elderly individuals presented with high LDL, triglycerides, and glycemia levels. Anthropometric parameters indicating increased-cardiovascular risk were positively correlated with CXCL-16, BMP-2, and IL-17 levels in overweight and obese middle-aged and elderly individuals.

Conclusion

This study provides evidence that CXCL-16, IL-17, and BMP-2 are potential plasma indicators of inflammatory status in middle-aged and elderly women; therefore, further investigation of obesity-related comorbidities is recommended. CXCL16, in particular, could be a potential marker for middle-aged and elderly individuals transitioning from eutrophic to overweight body types, which represents an asymptomatic and dangerous condition.

     

Validation of molecular markers linked to apospory in tetraploid races of bahiagrass, Paspalum notatum Flüggé

Tetraploid (2n = 4x = 40) races of Paspalum notatum Flüggé are important natural forage grasses for the tropical and subtropical areas of the Americas. Almost all natural accessions reproduce by obligate aposporous apomixis. Previous work on the species allowed the identification of several molecular markers completely linked to apospory, one component of apomictic reproduction. Moreover, after a fingerprinting characterization of a germplasm collection, 11 amplified fragment length polymorphism (AFLP) markers exclusive to apomictic accessions were detected. The objectives of this work were (1) to validate the presence of molecular markers linked to apospory in tetraploid races of different geographic origins, (2) to determine if markers specific to apomictic accessions were associated with the mode of reproduction, and (3) to develop single-locus markers of apospory that can be used for marker-assisted selection. Thirteen natural apomictic accessions were analyzed. Moreover, the parental plants Q4188 (non-aposporous) and Q4117 (aposporous) and 44 F1 progenies (36 non-aposporous, 8 aposporous) derived from them were used as a validation population. Nine markers [two random amplification of polymorphic DNA (RAPD) and seven AFLP] 100% linked to apospory in Q4117 were tested. Amplification reactions with the corresponding primers showed that all markers were present in the 13 aposporous (apomictic) accessions, but were absent in the non-aposporous controls. On the other hand, linkage analysis of the 11 AFLP markers specific to the apomictic accessions showed that all of them were linked in coupling to apospory (r = 0.00, LOD 13.245). Based on one AFLP (E36M37c), two sequence characterized amplification region (SCAR) markers (SPNA1 and SPNA2) co-segregating with the trait and present in the 13 apomictic accessions were developed. The presence of markers associated with apospory was conserved among tetraploid accessions of different geographic origins. Moreover, the single-locus markers SPNA1 and SPNA2 could be used for routine marker-assisted selection in hybrid populations segregating for apospory and to facilitate the isolation of apospory-related genes.     

Monitoring the convection coefficient in fermentative processes using numerical methods

Bioprocess and Biosystems Engineering - This work is based on the importance of monitoring the thermodynamic variables of sugarcane juice fermentation by Saccharomyces cerevisiae, using a numerical...     

Prophylactic corticosteroid to prevent pain flare in bone metastases treated by radiotherapy

BackgroundThe aim of this study was to evaluate the effectiveness of prophylactic corticosteroids to prevent pain flare (PF) in bone metastases treated with radiotherapy performing a meta-analysis of randomized clinical trials (RCT).Materials and methodsRCTs were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-analysis was performed to assess if corticosteroids reduce the PF, pain progression, and the mean of days with PF compared with the placebo. A p-value < 0.05 was considered significant.ResultsThree RCTs with a total of 713 patients treated were included. The corticosteroids reduced the occurrence of early PF 20.5% (51/248) versus 32% (80/250) placebo, OR = 0.55 (95% CI: 0.36–0.82, p = 0.002). The mean days of PF were reduced to 1.6 days (95% CI: 1.3–1.9, p = 0.0001). Prophylactic corticosteroids had more patients with no PF and no pain progression, OR = 1.63 (95% CI: 1.14–2.32, p = 0.007). No significant corticosteroids effect was observed for pain progression (p = ns) and late PF occurrence (p = ns).ConclusionProphylactic corticosteroids reduced the incidence of early PF, the days with PF, resulting in a superior rate of patients with no PF and no pain progression, but with no significant benefit for reducing pain progression or late PF occurrence.     

Control of phosphatidylcholine synthesis and the regulatory role of choline kinase in rat liver. Evidence from essential-fatty acid-deficient rats.

Choline kinase and phosphocholine cytidylytransferase catalyse the rate-limiting steps of the cytidine pathway for the synthesis of phosphatidylcholine [Infante (1977) Biochem. J. 167, 847--849]. Essential-fatty acid deficiency induces a 3.5-fold increase in the specific activity of choline kinase, whereas the specific activity of the cytidylytransferase remains unchanged in rat liver. This change in specific activity accounts for the calculated increase in flux through the cytidine pathway produced in vivo by the same dietary state [Trewhella & Collins (1973 Biochim. Biophys. Acta 296, 34--50], thus confirming the fact that choline kinase has a regulatory role in the cytidine pathway for the synthesis of phosphatidylcholine.     

Structure-function analysis of Escherichia coli DNA helicase I reveals non-overlapping transesterase and helicase domains

TraI (DNA helicase I) is an Escherichia coli F plasmid-encoded protein required for bacterial conjugative DNA transfer. The protein is a sequence-specific DNA transesterase that provides the site- and strand-specific nick required to initiate DNA strand transfer and a 5' to 3' DNA helicase that unwinds the F plasmid to provide the single-stranded DNA that is transferred from donor to recipient. Sequence comparisons with other transesterases and helicases suggest that these activities reside in the N- and C-terminal regions of TraI, respectively. Computer-assisted secondary structure probability analysis identified a potential interdomain region spanning residues 304-309. Proteins encoded by segments of traI, whose N or C terminus either flanked or coincided with this region, were purified and assessed for catalytic activity. Amino acids 1-306 contain the transesterase activity, whereas amino acids 309-1504 contain the helicase activity. The C-terminal 252 amino acids of the 1756-amino acid TraI protein are not required for either helicase or transesterase activity. Protein and nucleic acid sequence similarity searches indicate that the occurrence of both transesterase- and helicase-associated motifs in a conjugative DNA transfer initiator protein is rare. Only two examples (other than R100 plasmid TraI) were found: R388 plasmid TrwC and R46 plasmid (pKM101) TraH, belonging to the IncW and IncN groups of broad host range conjugative plasmids, respectively. The most significant structural difference between these proteins and TraI is that TraI contains an additional region of approximately 650 residues between the transesterase domain and the helicase-associated motifs. This region is required for helicase activity.     

CD8CD25 T cells reduce atherosclerosis in apoE(−/−) mice

Background

It is increasingly evident that CD8⁺ T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8⁺CD25⁺ T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8⁺CD25⁺ T cells in experimental atherosclerosis were investigated in this study.

Methods and results

CD8⁺CD25⁺ T cells were observed in atherosclerotic plaques of apoE(−/−) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8⁺CD25⁺ T cells from apoE(−/−) mice. Depletion of CD8⁺CD25⁺ from total CD8⁺ T cells rendered higher cytolytic activity of the remaining CD8⁺CD25⁻ T cells. Adoptive transfer of CD8⁺CD25⁺ T cells into apoE(−/−) mice suppressed the proliferation of splenic CD4⁺ T cells and significantly reduced atherosclerosis in recipient mice.

Conclusions

Our study has identified an athero-protective role for CD8⁺CD25⁺ T cells in experimental atherosclerosis.