Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency

Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier to eliminating HIV infection. These latent reservoirs, which include quiescent memory T cells and tissue-resident macrophages, represent a subset of cells with decreased or inactive proviral transcription. HIV proviral transcription is regulated at multiple levels including transcription initiation, polymerase recruitment, transcription elongation, and chromatin organization. How these biochemical processes are coordinated and their potential role in repressing HIV transcription along with establishing and maintaining latency are reviewed

Interleukin 2-inducible T cell kinase (ITK) facilitates efficient egress of HIV-1 by coordinating Gag distribution and actin organization

AbstractInterleukin 2-inducible T cell kinase (ITK) influences T cell signaling by coordinating actin polymerization and polarization as well as recruitment of kinases and adapter proteins. ITK regulates multiple steps of HIV-1 replication, including virion assembly and release. Fluorescent microscopy was used to examine the functional interactions between ITK and HIV-1 Gag during viral particle release. ITK and Gag colocalized at the plasma membrane and were concentrated at sites of F-actin accumulation and membrane lipid rafts in HIV-1 infected T cells. There was polarized staining of ITK, Gag, and actin towards sites of T cell conjugates. Small molecule inhibitors of ITK disrupted F-actin capping, perturbed Gag-ITK colocalization, inhibited virus like particle release, and reduced HIV replication in primary human CD4+ T cells. These data provide insight as to how ITK influences HIV-1 replication and suggest that targeting host factors that regulate HIV-1 egress provides an innovative strategy for controlling HIV infection

Theory blending: extended algorithmic aspects and examples

In Cognitive Science, conceptual blending has been proposed as an important cognitive mechanism that facilitates the creation of new concepts and ideas by constrained combination of available knowledge. It thereby provides a possible theoretical foundation for modeling high-level cognitive faculties such as the ability to understand, learn, and create new concepts and theories. Quite often the development of new mathematical theories and results is based on the combination of previously independent concepts, potentially even originating from distinct subareas of mathematics. Conceptual blending promises to offer a framework for modeling and re-creating this form of mathematical concept invention with computational means. This paper describes a logic-based framework which allows a formal treatment of theory blending (a subform of the general notion of conceptual blending with high relevance for applications in mathematics), discusses an interactive algorithm for blending within the framework, and provides several illustrating worked examples from mathematics

THE ROLE OF STAKEHOLDERS' INVOLVEMENT TO COMBAT DESERTIFICATION: A CASE STUDY IN THE APULIA REGION

Drought and desertification are largely considered as the major and most complex natural hazards. This is mainly due to the complexity of the web of impacts that ripple through too many sectors causing serious economic, social and environmental consequences. Hence, a wide range of actors are interested by drought effects. Empirical investigations in scientific literature have highlighted the differences between the stakeholder' perceptions of drought and desertification phenomena and the results of scientific – technical evaluation. There is no unique definition of the problem, but each individual has her/his own perception of drought and desertification, which is influenced by previous drought experiences and the mental models used to analyse these experiences. This could result in ambiguity in the definition of the problem. The ambiguity in drought and desertification definition could have a strong negative impact on the effectiveness of mitigation strategies. For these reasons, the involvement of stakeholder in the decision making process for drought and desertification management since its early stages has played a fundamental role. This work describes the experiences done to support drought and desertification management in the Apulia Region (Southern Italy). The methods and tools adopted in two different phases are described and the lessons learned during the process are discussed. The work is structured as follows: in section 1 there is an introduction and a description of the backgrounds regarding the project and the investigated territory. The objectives of the study and the empirical methodology applied state in section 2. Section 3 presents discussion and suggestion on decision making process. Conclusions and final remarks are proposed in section 4

Tra condizionalità e competitività: la rilevazione delle esigenze di consulenza delle aziende agricole pugliesi

L'articolo intende fornire un'analisi delle esigenze espresse dal sistema dei servizi di sviluppo agricolo sulla base delle esperienze che la Regione Puglia sta conducendo nell’ambito del Progetto Interregionale sui Servizi di Sviluppo. In particolare, l’intento è di valutare in termini quantitativi le priorità emergenti dagli interessi in gioco, al fine di agevolare il processo di programmazione degli interventi in termini di definizione degli obiettivi, dei contenuti specifici, delle fasce dei beneficiari e dei possibili soggetti erogatori dei servizi di sviluppo

Strength of T cell signaling regulates HIV-1 replication and establishment of latency.

A major barrier to curing HIV-1 is the long-lived latent reservoir that supports re-emergence of HIV-1 upon treatment interruption. Targeting this reservoir will require mechanistic insights into the establishment and maintenance of HIV-1 latency. Whether T cell signaling at the time of HIV-1 infection influences productive replication or latency is not fully understood. We used a panel of chimeric antigen receptors (CARs) with different ligand binding affinities to induce a range of signaling strengths to model differential T cell receptor signaling at the time of HIV-1 infection. Stimulation of T cell lines or primary CD4+ T cells expressing chimeric antigen receptors supported HIV-1 infection regardless of affinity for ligand; however, only signaling by the highest affinity receptor facilitated HIV-1 expression. Activation of chimeric antigen receptors that had intermediate and low binding affinities did not support provirus transcription, suggesting that a minimal signal is required for optimal HIV-1 expression. In addition, strong signaling at the time of infection produced a latent population that was readily inducible, whereas latent cells generated in response to weaker signals were not easily reversed. Chromatin immunoprecipitation showed HIV-1 transcription was limited by transcriptional elongation and that robust signaling decreased the presence of negative elongation factor, a pausing factor, by more than 80%. These studies demonstrate that T cell signaling influences HIV-1 infection and the establishment of different subsets of latently infected cells, which may have implications for targeting the HIV-1 reservoir