Tuesday, March 4, 2008

AIDS, analysis of a major discovery

AIDS, analysis of a major discovery announced as Communication is the lifeblood of conquests, no matter which, in short, we will not be surprised to see a variety of agencies, ten in total, including public Inserm, the NIH, and private, as Genome Canada and Genome Quebec , announced a major discovery on AIDS. See this press release which amateurism raise the ire of scientists Seraglio. But, no matter, science is done outside of press releases and knows decide itself discoveries that count, while his journals provide access to the results and ideas developed by specialists of the thing. While institutions rely on foals for research, for pocketing the media in a case where a breakthrough deemed spectacular emerges, which is the case with the laboratory in question, led by Dr. Sékaly. Deemed spectacular does not mean much, because only the medium-term future may decide on the significance of these results announced with great releases. But you should read in the text in the scientific journal Nature Medicine, where they were released What is it? In an investigation conducted from cellular materials from three types of individuals. The first sound, the latter carrying the HIV virus and monitored by the combination, the third, designated EC, stupidly brought by controllers elites instead of saying "resilient to the virus." Doctors have indeed found subjects carrying the virus but who, for reasons unknown, do not develop the disease, without being treated with anti-AIDS drug. That might say tiger science because those subjects are resisting is that their organization uses "mechanisms of resilience" that the others did not. Hence the obvious interest to make some comparative investigations. This was done. With an index as a result significant. A protein, designated FOXO3a, is involved in resistance to the virus. The mechanisms are complex (see graphics below) and a summary is required. The HIV infection produces a collapse of CD4 + T cells, T for thymus, the immune organ which it is derived, while B immune cells, bone marrow, are produced in the bone marrow. These CD4 cells provide a central immune memory. Their disappearance affects the defenses and produces AIDS. And the protein FOXO3a? Well, as a first step, the teams led by Sékaly showed his involvement in retaining the status of CD4 cells. This is actually quite complex. The protein exists in two forms, one saying crude, the other phosphorylated. The phosphorylation of proteins (adding a phosphoryl residue, a bit like an individual s'affuble a hat or a T-shirt siglé) is a cellular process as universal as the translation of RNA into proteins. As it happens, the non phosphorylated form undergoes a translocation (etymology, change of venue), and migrates into the nucleus after opening of pores in the nuclear membrane. Once in the nucleus, this protein is used as a signal to the cell apoptosis practise in other words, from destroying itself. Apoptosis is a process now well known. Some associate it with embryogenesis and the essence of life. It is the process of cell death is essential in the logic of the body. The mechanisms are very complex. FOXO3a induced protein in the nucleus of transcripts of genes promoting apoptosis. And resistance to AIDS? It involves a series of differences in the channels of intra-and intercellular communication, involving ultimately a significant difference at this famous FOXO3a protein which, in patients refractory to AIDS, a distinct phenotype doing it phosphoryl easier, as evidenced by the differences observed between patients and refractory (CBS). Thus, among these, the memories armada cells, the CD4 +, is maintained in good working order. In vitro studies suggest that this protein is linked to the survival and maintenance of CD4 cells, and only if, by some artificial interference, it inhibits the production process of the protein FOXO3a, the survival of these cells do memories is that better ensured. But this study, described in the article, was not very important. Except to say that everything is taking place and is assembled in a coherent, fitting and viable. Let me now make a few digressions and interpretations of scientific more personal. ---------------------- How should we understand this mechanism of apoptosis? First point. In the context of immune cells, the computer metaphor offers some insights. Memory is a key determinant in immune function. It is a sort of B. A.-BA of immunology and its applications, the vaccine. But in the case of AIDS and immunosuppression, it enters the engine room and reveal the secrets of the molecular mechanisms involved, a bit like an extra-terrestrial observer discovers one disk contains the long-term memory of 'computers and that, furthermore, the DDRam provides a short-term memory. The process of apoptosis found in the CD4 cells would seem obvious. In a computer, there are procedures to clear the memory misused and become useless. There is every reason to believe that, within the scope of immunity, mechanisms of self-producing cells that are no longer entitled to keep the immune memory too long (or to do redundant). Indeed, this is what justifies, reminders of vaccination against tetanus for example. FOXO3a The protein has been identified as one of the factors responsible for this natural and vital process of making the "basket" of immune memory became unnecessary, a mechanism which, in the case of AIDS, is substantially disrupted. Second point, resilience endogenous. The fact that subjects have developed defense mechanisms against the effects of the HIV virus seems to be in favour of a thesis of "intelligence molecular living", it is unclear what channels meta-biological, develops ways of resilience adapted to the threats of viral invasion and its deleterious process. The results reported in the article show, the fate of this immune mechanics can distinguish healthy subjects, patients and those who have the same fate as the healthy while carrying the virus, found in their cells and / or their genes, the key to survive naturally. Car mechanics immune resistance is significantly different from that of healthy subjects, for the same outcome in the end, health and lives. These few lines resonate philosophical implication of a transcendent standards of scientific understanding. Doubtless there food for thought on the development of adaptive mechanisms which, in this case, do not have a tenuous link with the environment because, once the virus integrated, the game is played between cells' body. Third point. The memory. And the role of phosphorylations. It so happens that FOXO3a protein, which is involved in immune memory is placed in a device found in the nervous system through the tau protein, which according to the degree of phosphorylation, induces cell death by apoptosis. According to available scientific evidence, tau protein also plays a role in the destruction of information one can imagine unnecessary, in the neural mechanisms, including synaptic fixtures. In mice, by stimulating the production of tau protein is induced dementia similar to Alzheimer's. Thus, as in the case of AIDS, there is dysfunction of the system and impaired memory in neurodegenerative diseases such as Alzheimer's and especially PSP. The common feature of these diseases is an alteration of mechanisms which, in normal times, for a healthy body, play a vital role in terms of memory management. And the other thing in common, at the molecular level, it is this role of phosphorylation, which, depending on the situation, is interpreted in one way or another. Thus, a cross-sectoral approach can draw similarities between different pathologies yet, but with three characteristics. A loss of memory, brain or immune, cellular processes of apoptosis, finally, key proteins, or FOXO Tau involved (through phosphorylation) in cell death supposed to maintain memory. Wonderful nature has been able to tame the molecular tools to manage communications and cellular issue, as far interpreted, these signals. As has been able to do so then, for transcendence and transformation, human beings with their languages. We are propelled into the mysteries of the next paradigm that I have delivered only modest keys at a modest but remarkable scientific discovery.

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