Characterization of variable regions of the Gp120 protein from HIV-1 subtype C virus variants obtained from individuals at different disease stages in Sub-Saharan Africa

Background: The development of a vaccine against HIV/AIDS capable of preventing virus infection has been hampered by the HIV envelope (Env) heterogeneity that makes it difficult to induce neutralizing antibodies against Env proteins from different HIV clades. Several studies have indicated that gp120 Env protein sequence tends to change considerably during the course of HIV disease which allows the virus to escape the immune responses. In order to define gp120 sequence changes, we have characterized the V1, V2, V4 and V5 variable regions of gp120 variants from 72 HIV-1-clade-C-infected subjects from South Africa and Swaziland, which were naïve to antiretroviral (ARV) therapy and at different disease stages. Sequence characteristics, such as aminoacid sequence length, presence of Putative N- Glycosylation Sites (PNGSs) and electric charge were investigated. Methods: According to the Avidity Index value and CD4+ T cell count, patients were classified for disease stage in three groups: recent, chronic and late stage, each one comprised of 24 patients. The V1 to V5 Env variable regions were directly PCR amplified from plasma virus RNA and sequenced. Results: A significant increase in the amino acid sequence length of V1 and V4 domains, and a corresponding increase of the “shifting” PNGSs were observed in the HIV variants obtained from individuals at chronic stage of disease, as compared to the recent infection group. Finally, a significant increase of the net electric positive charge of the V5 loop was found in the HIV variants from the group of subjects with late disease, as compared to the chronic disease group. Conclusion: We conclude that changes in sequence length, glycosylation pattern and net electrical charge in the variable V1, V4 and V5 regions of gp120 occur in the course of HIV infection, possibly in response to the pressure of the host immune response

What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?

The human immunodeficiency virus type 1 (HIV-1) trans-activator of transcription protein Tat is an important factor in viral pathogenesis. In addition to its function as the key trans-activator of viral transcription, Tat is also secreted by the infected cell and taken up by neighboring cells where it has an effect both on infected and uninfected cells. In this review we will focus on the relationship between the structure of the Tat protein and its function as a secreted factor. To this end we will summarize some of the exogenous functions of Tat that have been implicated in HIV-1 pathogenesis and the impact of structural variations and viral subtype variants of Tat on those functions. Finally, since in some patients the presence of Tat-specific antibodies or CTL frequencies are associated with slow or non-progression to AIDS, we will also discuss the role of Tat as a potential vaccine candidate, the advances made in this field, and the importance of using a Tat protein capable of eliciting a protective or therapeutic immune response to viral challenge

Original Article

The pancreas taken from the frog (Rana nigromaculata) was fixed in 1% OsO_4 and sliced into ultrathin sections for electron microscopic studies. The following observations were made: 1. A great \u27number of minute granules found in the cytoplasm of a pancreatic cell were called the microsomes, which were divided into two types, the C-microsome and S-microsome. 2. Electron microsopic studies of the ergastoplasm showed that it is composed of the microsome granules and A-substance. The microsomes were seen embedded in the A-substance which was either filamentous or membranous. The membranous structure, which was called the Am-membrane, was seen to form a sac, with a cavity of varying sizes, or to form a lamella. 3. The Am-membrane has close similarity to α-cytomembrane of Sjostrand, except that the latter is rough-surfaced. It was deduced that the Am-membrane, which is smooth-surfaced, might turn into the rough-surfaced α-cytomembrane. 4. There was the Golgi apparatus in the supranuclear region of a pancreatic cell. It consisted of the Golgi membrane, Golgi vacuole and. Golgi vesicle. 5. The mitochondria of a pancreatic cell appeared like long filaments, and some of them were seen to ramify. 6. The membrane of mitochondria, i. e. the limiting membrane, consisted of the Ammembrane. The mitochondria contained a lot of A-substances, as well as the C-microsomes and S-microsomes. When the mitochondria came into being, there appeared inside them chains of granules, which appeared like strips of beads, as the outgrowths of the A-substance and the microsome granules attached to the Am-membrane. They are the so-called cristae mitochondriales. 7. The secretory granules originate in the microsomes. They came into being when the microsomes gradually thickened and grew in size as various substances became adhered to them. Some of the secretory granules were covered with a membrane and appeared like what they have called the intracisternal granule of Palade.It seemed that this was a phenomenon attendant upon the dissolution and liqutefaction of the secretory granule. 8. Comparative studies were made of the ergastoplasm of the pancreatic cells from the frogs in hibernation, the frogs artificially hungered, the frogs which were given food after a certain period of fasting, the frogs to which pilocarpine was given subcutaneously, and the very young, immature frogs. The studies revealed that the ergastoplasm of the pancreatic cells greatly varied in form with the difference in nutritive condition and with different developmental stages of the cell. The change in form and structure occured as a result of transformation of the microsomes and A-substance. The ergastoplasm, even after it has come into being, might easily be inactivated if nutrition is defective. The ergastoplasm is concerned in the secretory mechanism, which is different from the secretory phenomenon of the secretory granules. It would seem that structurally the mitochondria have no direct relation to this mechanism

Competenze culturali per un Umanesimo Digitale. La via italiana verso Europa 2018. In: Patrimoni culturali nell’era digitale. Memorie, culture umanistiche e tecnologia. Cultural Heritage in the Digital Age. Memory, Humanities and Technologies. Settimo Convegno Annuale AIUCD 2018, Bari, 31 gennaio – 2 febbraio 2018. Book of Abstracts.

Il panel intende proporre un confronto tra i rappresentanti dei principali soggetti pubblici e privati nazionali impegnati nella ricerca, formazione, gestione, tutela, valorizzazione del digital cultural heritage e del patrimonio culturale tangibile e intangibile, sul tema dei saperi da integrare nella formazione del sistema di competenze umanistiche digitali già oggi indispensabile per gestire, tutelare e valorizzare il cultural heritage nell'evo digitale contemporaneo, garantendo nel contempo la conservazione e la sopravvivenza nel futuro del nuovo patrimonio culturale digitale