38 research outputs found
Cellular factors that interact with acetylated integrase: new insights in HIV - 1 integration
No full textSingle cell imaging of HIV provirus (SCIP)
No full textRecent advances in fluorescence microscopy provided tools for the investigation and the analysis of the viral replication steps in the cellular context. In the HIV field, the current visualization systems successfully achieve the fluorescent labeling of the viral envelope and proteins, but not the genome. Here, we developed a system able to visualize the proviral DNA of HIV-1 through immunofluorescence detection of repair foci for DNA double-strand breaks specifically induced in the viral genome by the heterologous expression of the I-SceI endonuclease. The system for Single-Cell Imaging of HIV-1 Provirus, named SCIP, provides the possibility to individually track integrated-viral DNA within the nuclei of infected cells. In particular, SCIP allowed us to perform a topological analysis of integrated viral DNA revealing that HIV-1 preferentially integrates in the chromatin localized at the periphery of the nuclei.sponsorship: The authors are grateful to the laboratory of W. Thys and M. Giacca for valuable discussion and to A. Calvello for technical assistance. This work was supported by grants from the European Union Seventh Framework Programme (THINC, Health-2008-201032), by the Istituto Superiore di Sanita Italian AIDS Program (Grant 40H90), by the Provincia Autonoma di Trento (COFUND Project, Team 2009 - Incoming), and by FIRB 2008 Futuro in Ricerca (RBFR08HSWG). (European Union Seventh Framework Programme (THINC)|Health-2008-201032, Istituto Superiore di Sanita Italian AIDS Program|40H90, Provincia Autonoma di Trento (COFUND Project), FIRB|RBFR08HSWG)status: Publishe
Tau-dependent HDAC1 nuclear reduction is associated with altered VGluT1 expression
No full textDuring AD pathology, Tau protein levels progressively increase from early pathological stages. Tau altered expression causes an unbalance of Tau subcellular localization in the cytosol and in the nuclear compartment leading to synaptic dysfunction, neuronal cell death and neurodegeneration as a consequence. Due to the relevant role of epigenetic remodellers in synaptic activity in physiology and in neurodegeneration, in particular of TRIM28 and HDAC1, we investigated the relationship between Tau and these epigenetic factors. By molecular, imaging and biochemical approaches, here we demonstrate that Tau altered expression in the neuronal cell line SH-SY5y does not alter TRIM28 and HDAC1 expression but it induces a subcellular reduction of HDAC1 in the nuclear compartment. Remarkably, HDAC1 reduced activity modulates the expression of synaptic genes in a way comparable to that observed by Tau increased levels. These results support a competitive relationship between Tau levels and HDAC1 subcellular localization and nuclear activity, indicating a possible mechanism mediating the alternative role of Tau in the pathological alteration of synaptic genes expression
Preference and Perception of Mobile Health Applications Educating African American Women on Sexual and Reproductive Health
No full textThe Preference and Perception of Mobile Health Applications Educating African American Women on Sexual and Reproductive Health First author: Allison Griswold Co-author: Awatef Ben Ramadan Abstract Background: Previous studies have found that African American women are affected by sexually transmitted diseases and reproductive health issues at a higher rate than any other race. Study Aims: To increase awareness of cultural barriers, and to explore the need for medically accurate sexual and reproductive health information through mobile health applications. Methods: The Institutional Review Board approved an anonymous online survey using convenience sampling of African American women between the ages of 18-50. Respondents answered questions regarding past sexual education course experience, use of women�s health applications, interest in health messages, the importance of health information, personal knowledge satisfaction, and preference for receiving information. The study results presented as graphs, which were generated through excel spreadsheets. Results: Of the 159 respondents that completed the survey, 38.5% currently use any form of women�s mobile health application very frequently. However, 65.8% are interested in receiving information on sexual and reproductive health through women�s health applications. Of the 159 respondents, only 27% were very satisfied with their current sexual and reproductive health knowledge. Conclusion: This study proves that African American women are open to learning and gaining sexual and reproductive facts through mobile applications. Keywords: African American women, period trackers, mobile health applications, sexual health, reproductive healt
Does the Use of Health Apps to Monitor Hypertension Improve the Knowledge, Attitudes, and Practices of African-Americans towards Hypertension Self- and Active-Management
No full textShowcase: Does the Use of Health Apps to Monitor Hypertension Improve the Knowledge, Attitudes, and Practices of African-Americans towards Hypertension Self- and Active-Management First Author: Jacquetta Lindsey Co-author: Awatef Ben Ramadan Background: Despite the many medical advancements available today, cardiovascular disease remains the leading cause of death in the African American community. Hypertension is considered the most modifiable cardiovascular disease, and African Americans are disproportionately affected by this disease � 43% compared to 28% of White Americans. Study Aim: To determine if the knowledge, attitudes, and practices (KAP) of African Americans towards hypertension self-management and active engagement in the healthcare process improved with the use of a mobile health application to monitor their condition. Methods: Study participants were recruited from community-based resources. Participants first completed a pre-survey to determine their baseline KAP. Next, they downloaded the AVAX Blood Pressure Diary to daily monitor their blood pressure. Lastly, participants completed the post-survey and system user satisfaction (SUS) survey on the blood pressure application. Results: Majority of the participants were women (70%) with 50% on medication for their hypertension. Most of the participants (87.5%) believed that their hypertension was better managed after using the health app. The average SUS score for the hypertension mobile health application was 89.75. Conclusion: It appears that the mobile health application assisted participants with monitoring their blood pressure daily and being aware of changes that needed to be made to improve their self-management
The TRIM family protein KAP1 inhibits HIV-1 integration.
No full textThe integration of viral cDNA into the host genome is a critical step in the life cycle of HIV-1. This step is catalyzed by integrase (IN), a viral enzyme that is positively regulated by acetylation via the cellular histone acetyl transferase (HAT) p300. To investigate the relevance of IN acetylation, we searched for cellular proteins that selectively bind acetylated IN and identified KAP1, a protein belonging to the TRIM family of antiviral proteins. KAP1 binds acetylated IN and induces its deacetylation through the formation of a protein complex which includes the deacetylase HDAC1. Modulation of intracellular KAP1 levels in different cell types including T cells, the primary HIV-1 target, revealed that KAP1 curtails viral infectivity by selectively affecting HIV-1 integration. This study identifies KAP1 as a cellular factor restricting HIV-1 infection and underscores the relevance of IN acetylation as a crucial step in the viral infectious cycle
GCN5-dependent acetylation of HIV-1 integrase enhances viral integration
No full textAbstract Background An essential event during the replication cycle of HIV-1 is the integration of the reverse transcribed viral DNA into the host cellular genome. Our former report revealed that HIV-1 integrase (IN), the enzyme that catalyzes the integration reaction, is positively regulated by acetylation mediated by the histone acetyltransferase (HAT) p300. Results In this study we demonstrate that another cellular HAT, GCN5, acetylates IN leading to enhanced 3'-end processing and strand transfer activities. GCN5 participates in the integration step of HIV-1 replication cycle as demonstrated by the reduced infectivity, due to inefficient provirus formation, in GCN5 knockdown cells. Within the C-terminal domain of IN, four lysines (K258, K264, K266, and K273) are targeted by GCN5 acetylation, three of which (K264, K266, and K273) are also modified by p300. Replication analysis of HIV-1 clones carrying substitutions at the IN lysines acetylated by both GCN5 and p300, or exclusively by GCN5, demonstrated that these residues are required for efficient viral integration. In addition, a comparative analysis of the replication efficiencies of the IN triple- and quadruple-mutant viruses revealed that even though the lysines targeted by both GCN5 and p300 are required for efficient virus integration, the residue exclusively modified by GCN5 (K258) does not affect this process. Conclusions The results presented here further demonstrate the relevance of IN post-translational modification by acetylation, which results from the catalytic activities of multiple HATs during the viral replication cycle. Finally, this study contributes to clarifying the recent debate raised on the role of IN acetylated lysines during HIV-1 infection.</p
Macrophage biology plays a central role during ionizing radiation-elicited tumor response
No full textRadiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied. The mechanisms underlying radiation-induced macrophage activation remain largely elusive. Various molecular players such as NF-κB, MAPKs, p53, reactive oxygen species, inflammasomes have been involved in these processes. The skewing to a pro-inflammatory phenotype thus results in the activation of anti-tumor immune response and enhanced radiotherapy effect. Therefore, a comprehensive understanding of the mechanism of radiation-induced macrophage activation and its role in tumor response to radiation therapy is crucial for the development of new therapeutic strategies to enhance radiation therapy efficacy
