DNA dependent protein kinase (DNA-PK) enhances HIV transcription by promoting RNA polymerase II activity and recruitment of transcription machinery at HIV LTR.

Despite reductions in mortality from the use of highly active antiretroviral therapy (HAART), the presence of latent or transcriptionally silent proviruses prevents HIV cure/eradication. We have previously reported that DNA-dependent protein kinase (DNA-PK) facilitates HIV transcription by interacting with the RNA polymerase II (RNAP II) complex recruited at HIV LTR. In this study, using different cell lines and peripheral blood mononuclear cells (PBMCs) of HIV-infected patients, we found that DNA-PK stimulates HIV transcription at several stages, including initiation, pause-release and elongation. We are reporting for the first time that DNA-PK increases phosphorylation of RNAP II C-terminal domain (CTD) at serine 5 (Ser5) and serine 2 (Ser2) by directly catalyzing phosphorylation and by augmenting the recruitment of the positive transcription elongation factor (P-TEFb) at HIV LTR. Our findings suggest that DNA-PK expedites the establishment of euchromatin structure at HIV LTR. DNA-PK inhibition/knockdown leads to the severe impairment of HIV replication and reactivation of latent HIV provirus. DNA-PK promotes the recruitment of Tripartite motif-containing 28 (TRIM28) at LTR and assists the release of paused RNAP II through TRIM28 phosphorylation. These results provide the mechanisms through which DNA-PK controls the HIV gene expression and, likely, can be extended to cellular gene expression, including during cell malignancy, where the role of DNA-PK has been well-established

Odd Perfect Numbers are Greater than 10^1500

International audienceBrent, Cohen, and te Riele proved in 1991 that an odd perfect number N is greater than 10^300. We modify their method to obtain N > 10^1500. We also obtain that N has at least 101 not necessarily distinct prime factors and that its largest component (i.e. divisor p^a with p prime) is greater than 10^62

On the number of prime factors of an odd perfect number

International audienceLet ω(n) and Ω(n) denote, respectively, the total number of prime factors and the number of distinct prime factors of the integer n. Euler proved that an odd perfect number N is of the form N = pᶱm² where p ≡ e ≡ 1 (mod 4), p is prime, and p ∤ m. This implies that Ω(N) ≥ 2ω(N) − 1. We. We prove that Ω(N) ≥ (18ω(N) −31) /7andΩ(N) ≥ 2ω(N) + 51

Spatiotemporal dynamics of terrestrial invertebrate assemblages in the riparian zone of the Wewe river, Ashanti region, Ghana

This study assessed invertebrate response to disturbances in the riparian zone of the Wewe river, using geometric series, rarefaction, Renyi diversity, and CCA models. We sampled 2,077 individuals (dry season) and 2,282 (wet season) belonging to 16 invertebrate orders. The severely disturbed habitat registered the highest individuals (n = 1,999), while the least was the moderately disturbed habitat (n = 740). Seasonal assemblages were not significantly different. Fire, farming, tree felling, and erosion explained 66.8% and 60.55% in the dry and wet seasons, respectively, of variations in invertebrate assemblages. This suggests threats to the invertebrate community and the riparian ecosystem health by anthropogenic interventions

DNA-PK Inhibition Potently Represses HIV Transcription and Replication

DNA-dependent protein kinase (DNA-PK), a nuclear protein kinase that specifically requires association with DNA for its kinase activity, plays important roles in the regulation of different DNA transactions, including transcription, replication and DNA repair, as well as in the maintenance of telomeres. We reported DNA-PK facilitated HIV transcription by interacting with the RNA polymerase II (RNAP II) complex recruited to HIV LTR and identified potential DNA-PK targets within the carboxyl terminal domain (CTD) of RNAP II through kinase assays. In our current study, DNA-PK inhibition via highly specific small molecule inhibitors replicated the shRNA-mediated abrogation of both HIV transcription and replication in latently infected myeloid and lymphoid cell lines, the main cell types targeted by HIV. These inhibitors also impaired HIV replication in primary CD4+ T-cells. Pre-treatment of the HIV-infected cell lines with the DNA-PK inhibitors also resulted in severe impairment of the phosphorylation of the serine 2 and serine 5 of the RNAP II CTD upon stimulation. Chromatin immunoprecipitation (ChIP) analysis showed the inhibition of DNA-PK activity led to the establishment of transcriptionally repressive heterochromatin structures at the HIV LTR. These findings confirm the important role of DNA-PK in HIV transcription and replication and excitingly we have identified two strong inhibitors of DNA-PK that successfully limit the reactivation of latently HIV-infected cells. In light of the fact that these transcriptionally silent proviruses are well protected from both the immune system and HAART regimens, which prevents complete eradication of the virus, we present strong evidence for the inclusion of DNA-PK inhibitors as supplements to HAART regimens, to enhance their restriction of HIV replication

Abstracts of Tanzania Health Summit 2020

This book contains the abstracts of the papers/posters presented at the Tanzania Health Summit 2020 (THS-2020) Organized by the Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender, and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); & Tindwa Medical and Health Services (TMHS) held on 25–26 November 2020. The Tanzania Health Summit is the annual largest healthcare platform in Tanzania that attracts more than 1000 participants, national and international experts, from policymakers, health researchers, public health professionals, health insurers, medical doctors, nurses, pharmacists, private health investors, supply chain experts, and the civil society. During the three-day summit, stakeholders and decision-makers from every field in healthcare work together to find solutions to the country’s and regional health challenges and set the agenda for a healthier future. Summit Title: Tanzania Health SummitSummit Acronym: THS-2020Summit Date: 25–26 November 2020Summit Location: St. Gasper Hotel and Conference Centre in Dodoma, TanzaniaSummit Organizers: Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); & Tindwa Medical and Health Services (TMHS)