Correction to: Clinical management of ageing people living with HIV in Europe: the view of the care providers.

info:eu-repo/semantics/publishedVersio

Androgen-Regulated Transcriptional Control of Sialyltransferases in Prostate Cancer Cells

The expression of gangliosides is often associated with cancer progression. Sialyltransferases have received much attention in terms of their relationship with cancer because they modulate the expression of gangliosides. We previously demonstrated that GD1a production was high in castration-resistant prostate cancer cell lines, PC3 and DU145, mainly due to their high expression of β-galactoside α2,3-sialyltransferase (ST3Gal) II (not ST3Gal I), and the expression of both ST3Gals was regulated by NF-κB, mainly by RelB. We herein demonstrate that GD1a was produced in abundance in cancerous tissue samples from human patients with hormone-sensitive prostate cancers as well as castration-resistant prostate cancers. The expression of ST3Gal II was constitutively activated in castration-resistant prostate cancer cell lines, PC3 and DU145, because of the hypomethylation of CpG island in its promoter. However, in androgen-depleted LNCap cells, a hormone-sensitive prostate cancer cell line, the expression of ST3Gal II was silenced because of the hypermethylation of the promoter region. The expression of ST3Gal II in LNCap cells increased with testosterone treatment because of the demethylation of the CpG sites. This testosterone-dependent ST3Gal II expression was suppressed by RelB siRNA, indicating that RelB activated ST3Gal II transcription in the testosterone-induced demethylated promoter. Therefore, in hormone-sensitive prostate cancers, the production of GD1a may be regulated by androgen. This is the first report indicating that the expression of a sialyltransferase is transcriptionally regulated by androgen-dependent demethylation of the CpG sites in its gene promoter

FOX-2 Dependent Splicing of Ataxin-2 Transcript Is Affected by Ataxin-1 Overexpression

Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co-immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX-2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1

Clinical management of ageing people living with HIV in Europe: the view of the care providers

BACKGROUND: Although guidelines for the management of HIV infection include recommendations for aging people living with HIV (PLWH), clinical practice of European HIV care providers may vary. METHOD: We performed a study using a 3-phase Delphi methodology by involving a panel of clinicians with expertise in HIV infection clinical management. The main aim of the study was to assess the care provider prospective on how HIV clinical care should be delivered to ageing PLWH. The first phase involved ten clinicians to identify HIV comorbidities of interest. The second and third phases recruited clinicians virtually via a web-based questionnaire that included 137 questions focussed on 11 comorbidities (e.g. cardiovascular disease, pulmonary disease, etc.). RESULTS: Results were analysed thematically and consensus (or not) among European physicians reported. Ninety-seven and 85 responses were collected in phase 2 and 3, respectively. High levels of agreement were found among clinical care providers across Europe and with the European AIDS Conference Society guidelines regarding key items of clinical management of comorbidities in ageing PLWH. CONCLUSION: However, we identified some important gaps, such as the lack of standardisation or implementation of the assessment of frailty or menopause, which are emerging as important factors to optimise ageing PLWH clinical care. Further studies are warranted to confirm whether intensified screening translates into HIV morbidity advances.info:eu-repo/semantics/publishedVersio

Revealing the biotechnological potential of Delftia sp. JD2 by a genomic approach

Delftia sp. JD2 is a chromium-resistant bacterium that reduces Cr(VI) to Cr(III), accumulates Pb(II), produces the phytohormone indole-3-acetic acid and siderophores, and increases the plant growth performance of rhizobia in co-inoculation experiments. We aimed to analyze the biotechnological potential of JD2 using a genomic approach. JD2 has a genome of 6.76Mb, with 6,051 predicted protein coding sequences and 93 RNA genes (tRNA and rRNA). The indole-acetamide pathway was identified as responsible for the synthesis of indole-3-acetic acid. The genetic information involved in chromium resistance (the gene cluster, chrBACF,) was found. At least 40 putative genes encoding for TonB-dependent receptors, probably involved in the utilization of siderophores and biopolymers, and genes for the synthesis, maturation, exportation and uptake of pyoverdine, and acquisition of Fe-pyochelin and Fe-enterobactin were also identified. The information also suggests that JD2 produce polyhydroxybutyrate, a carbon reserve polymer commonly used for manufacturing petrochemical free bioplastics. In addition, JD2 may degrade lignin-derived aromatic compounds to 2-pyrone-4,6-dicarboxylate, a molecule used in the bio-based polymer industry. Finally, a comparative genomic analysis of JD2, Delftia sp. Cs1-4 and Delftia acidovorans SPH-1 is also discussed. The present work provides insights into the physiology and genetics of a microorganism with many potential uses in biotechnology