ЗАСАДИ УПРАВЛІННЯ У СФЕРІ ЗАБЕЗПЕЧЕННЯ РОЗВИТКУ СІЛЬСЬКИХ ПРИКОРДОННИХ ТЕРИТОРІЙ

The article deals with the principles of management of the process of ensuring the balanced development of territorial economic systems, in particular, the border areas of the countryside. The prerequisites of the use of competitive advantages of rural border areas in the conditions of integration and convergence have been substantiated. In order to reflect the diversity of aspects of the development of the territorial economic system, in particular the rural border areas, and the generalization of existing experience, the classification species characteristics of the development of the studied systems have been systematized. The necessity of combining the interests of the state, bodies of state administration, local self-government and the territorial community has been noted, in the direction of providing effective management in the process of functioning of economic structures within the boundaries of rural border territories and balanced development of territorial economic systems in general.В статье рассмотрены основы управления процессом обеспечения сбалансированного развития территориальных экономических систем, в частности приграничных территорий сельской местности. Обоснованны предпосылки использования конкурентных преимуществ сельских приграничных территорий в условиях интеграции и конвергенции. С целью отображения многообразия аспектов развития территориальной экономической системы, в том числе сельских приграничных территорий, и обобщения существующего опыта, систематизированы классификационные видовые признаки развития исследуемых систем. Отмечено необходимость сочетания интересов государства, органов государственного управления, местного самоуправления и территориальной общины в направлении обеспечения эффективного управления в процессе функционирования хозяйствующих структур в пределах сельских приграничных территорий и сбалансированного развития территориальных экономических систем в целом.У статті розглянуто засади управління процесом забезпечення збалансованого розвитку територіальних економічних систем, зокрема прикордонних територій сільської місцевості. Обґрунтовано передумови використання конкурентних переваг сільських прикордонних територій в умовах інтеграції й конвергенції. З метою відображення багатоманітності аспектів розвитку територіальної економічної системи, зокрема й сільських прикордонних територій, та узагальнення існуючого досвіду, систематизовано класифікаційні видові ознаки розвитку досліджуваних систем. Відмічено необхідність поєднання інтересів держави, органів державного управління, місцевого самоврядування та територіальної громади, у напрямі забезпечення дієвого управління у процесі функціонування господарюючих структур в межах сільських прикордонних територій та збалансованого розвитку територіальних економічних систем в цілому

Latency reversal and viral clearance to cure HIV-1

Research toward a cure for human immunodeficiency virus type 1 (HIV-1) infection has joined prevention and treatment efforts in the global public health agenda. A major approach to HIV eradication envisions antiretroviral suppression, paired with targeted therapies to enforce the expression of viral antigen from quiescent HIV-1 genomes, and immunotherapies to clear latent infection. These strategies are targeted to lead to viral eradication—a cure for AIDS. Paired testing of latency reversal and clearance strategies has begun, but additional obstacles to HIV eradication may emerge. Nevertheless, there is reason for optimism that advances in long-acting antiretroviral therapy and HIV prevention strategies will contribute to efforts in HIV cure research and that the implementation of these efforts will synergize to markedly blunt the effect of the HIV pandemic on society

Combined approaches for HIV cure

A serious effort has begun to develop therapies that may be capable of eradicating established HIV infection in man. Because of the biological complexity of HIV infection that persists despite potent antiretroviral therapy, it is widely believed that if such therapies can be developed they will involve complex, multimodality approaches. We highlight some of the recent studies in this effort

A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges

Pre-exposure prophylaxis (PrEP) using antiretroviral drugs (ARVs) has been shown to reduce HIV transmission in people at high risk of HIV infection. Adherence to PrEP strongly correlates with the level of HIV protection. Long-acting injectable ARVs provide sustained systemic drug exposures over many weeks and can improve adherence due to infrequent parenteral administration. Here, we evaluated a new long-acting formulation of raltegravir for prevention of vaginal HIV transmission

siRNA Screening of a Targeted Library of DNA Repair Factors in HIV Infection Reveals a Role for Base Excision Repair in HIV Integration

Host DNA repair enzymes have long been assumed to play a role in HIV replication, and many different DNA repair factors have been associated with HIV. In order to identify DNA repair pathways required for HIV infection, we conducted a targeted siRNA screen using 232 siRNA pools for genes associated with DNA repair. Mapping the genes targeted by effective siRNA pools to well-defined DNA repair pathways revealed that many of the siRNAs targeting enzymes associated with the short patch base excision repair (BER) pathway reduced HIV infection. For six siRNA pools targeting BER enzymes, the negative effect of mRNA knockdown was rescued by expression of the corresponding cDNA, validating the importance of the gene in HIV replication. Additionally, mouse embryo fibroblasts (MEFs) lacking expression of specific BER enzymes had decreased transduction by HIV-based retroviral vectors. Examining the role BER enzymes play in HIV infection suggests a role for the BER pathway in HIV integration

Uso racional y eficiencia energética aplicado a hoteles

Fil: Maciel, Aldo Daniel. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales; Argentina.Fil: Poggi, Eduardo Roberto. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales; Argentina.Fil: Gutiérrez, Fernando Manuel. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales; Argentina.Fil: Hazuda Yanina Victoria. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales; Argentina.El uso eficiente de la energía eléctrica es un imperativo ambiental y una exigencia competitiva para el sector turístico en general y para la industria hotelera en particular. El creciente consumo energético propio de la necesidad de satisfacer la demanda de confort, sitúa a la energía como un insumo clave que impacta de manera directa en la satisfacción de los clientes, los costos de explotación del negocio, la rentabilidad de la empresa y el medio ambiente. De tal manera, el debate acerca del uso eficiente de la energía no sólo es oportuno sino relevante

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA–positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART

Cellular Gene Modulation of HIV-Infected CD4 T Cells in Response to Serial Treatment with the Histone Deacetylase Inhibitor Vorinostat

Histone deacetylase inhibitors (HDACi) are the most widely studied HIV latency-reversing agents (LRAs). The HDACi suberoylanilide hydroxamic acid (vorinostat [VOR]) has been employed in several clinical HIV latency reversal studies, as well as in vitro models of HIV latency, and has been shown to effectively induce HIV RNA and protein expression. Despite these findings, response to HDACi can vary, particularly with intermittent dosing, and information is lacking on the relationship between the host transcriptional response and HIV latency reversal. Here, we report on global gene expression responses to VOR and examine the longevity of the transcriptional response in various cellular models. We found that many genes are modulated at 6 h post-VOR treatment in HCT116, Jurkat, and primary resting CD4 T cells, yet return to baseline levels after an 18-h VOR-free period. With repeat exposure to VOR in resting CD4 T cells, we found similar and consistent transcriptional changes at 6 h following each serial treatment. In addition, serial exposure in HIV-infected suppressed donor CD4 T cells showed consistent transcriptional changes after each exposure to VOR. We identified five host genes that were strongly and consistently modulated following histone deacetylase (HDAC) inhibition; three (H1F0, IRGM, and WIPI49) were upregulated, and two (PHF15 and PRDM10) were downregulated. These genes demonstrated consistent modulation in peripheral blood mononuclear cell (PBMC) samples from HIV-positive (HIV+) participants who received either single or multiple doses of 400 mg of VOR. Interestingly, the host transcriptional response did not predict induction of cell-associated HIV RNA, suggesting that other cellular factors play key roles in HIV latency reversal in vivo despite robust HDACi pharmacological activity. IMPORTANCE Histone deacetylase inhibitors are widely studied HIV latency-reversing agents (LRAs). VOR, an HDACi, induces histone acetylation and chromatin remodeling and modulates host and HIV gene expression. However, the relationship between these events is poorly defined, and clinical studies suggest diminished HIV reactivation in resting CD4 T cells with daily exposure to VOR. Our study provides evidence that VOR induces a consistent level of host cell gene transcription following intermittent exposure. In addition, in response to VOR exposure a gene signature that was conserved across single and serial exposures both in vitro and in vivo was identified, indicating that VOR can consistently and reproducibly modulate transcriptional host responses. However, as the HIV response to HDACi declines over time, other factors modulate viral reactivation in vivo despite robust HDAC activity. The identified host gene VOR biomarkers can be used for monitoring the pharmacodynamic activity of HDAC inhibitors