Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine

BACKGROUND: One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. METHODOLOGY AND FINDINGS: To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection. SIGNIFICANCE: Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity

Nucleo-cytoplasmic transport of proteins and RNA in plants

Merkle T. Nucleo-cytoplasmic transport of proteins and RNA in plants. Plant Cell Reports. 2011;30(2):153-176.Transport of macromolecules between the nucleus and the cytoplasm is an essential necessity in eukaryotic cells, since the nuclear envelope separates transcription from translation. In the past few years, an increasing number of components of the plant nuclear transport machinery have been characterised. This progress, although far from being completed, confirmed that the general characteristics of nuclear transport are conserved between plants and other organisms. However, plant-specific components were also identified. Interestingly, several mutants in genes encoding components of the plant nuclear transport machinery were investigated, revealing differential sensitivity of plant-specific pathways to impaired nuclear transport. These findings attracted attention towards plant-specific cargoes that are transported over the nuclear envelope, unravelling connections between nuclear transport and components of signalling and developmental pathways. The current state of research in plants is summarised in comparison to yeast and vertebrate systems, and special emphasis is given to plant nuclear transport mutants

Od informacji do innowacji. Działanie polskich ombudsmanów na rzecz praw osób niepełnosprawnych

Human rights are one of the cornerstones of a democratic state. They have character: natural and inalienable. Human rights also apply to specific moments in which is a specific person, which is: a child, employee, patient and a person with a disability. The last two categories have a special character. They relate to moments in human life, in which he experiences pain and suffering. In Poland, for nearly thirty years operating office of the Ombudsman. Thanks to the work of successive ombudsmen, society was and still is learned in the field of human rights and freedoms. In recent years, it can be seen changes in the Polish system of human rights protection. There are new types of ombudsmen. With regard to persons with disabilities, there is new, innovative form of action. It is a method of training the skills of being a spokesman own rights. How work the above, still forming the Polish system of ombudsmen? How individual spokesmen work? Are their initiatives effective?Prawa człowieka stanowią jeden z fundamentów państwa demokratycznego. Posiadają one charakter: przyrodzony oraz niezbywalny. To dzięki nim człowiek może upominać się o przynależne mu dobra. Prawa człowieka odnoszą się także do szczególnych momentów, w jakich znajduje się konkretna osoba będąca: dzieckiem, pracownikiem, pacjentem oraz osobą niepełnosprawną. Dwie ostatnie kategorie mają wyjątkowy charakter. Dotyczą one chwil w życiu człowieka, w których doświadcza on bólu oraz cierpienia. W Polsce od prawie trzydziestu lat funkcjonuje urząd Rzecznika Praw Obywatelskich. To dzięki pracy kolejnych rzeczników, społeczeństwo zostało i nadal jest edukowane w zakresie praw i wolności człowieka. W ciągu ostatnich lat można zauważyć zmiany w polskim systemie ochrony praw człowieka. Pojawili się nowi, specjalni rzecznicy praw. W odniesieniu do osób niepełnosprawnych pojawiła się z kolei nowa, innowacyjna forma działania. Mowa o trenowaniu umiejętności bycia rzecznikiem własnych praw . Jak zatem działa powyższy, nadal kształtujący się system polskich rzeczników? W jaki sposób poszczególni rzecznicy działają? Czy ich inicjatywy są skuteczne

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity.

Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza-Rev and cryopreserved. Subsequent stem cell mobilization was followed by high-dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT