Systematic Analysis of the Effect of Genomic Knock-Out of Non-Essential Promiscuous HAD-Like Phosphatases YcsE, YitU and YwtE on Flavin and Adenylate Content in Bacillus Subtilis.

Studying the metabolic role of non-essential promiscuous enzymes is a challenging task, as genetic manipulations usually do not reveal at which point(s) of the metabolic network the enzymatic activity of such protein is beneficial for the organism. Each of the HAD-like phosphatases YcsE, YitU and YwtE of Bacillus subtilis catalyzes the dephosphorylation of 5-amino-6-ribitylamino-uracil 5'-phosphate, which is essential in the biosynthesis of riboflavin. Using CRISPR technology, we have found that the deletion of these genes, individually or in all possible combinations failed to cause riboflavin auxotrophy and did not result in significant growth changes. Analysis of flavin and adenylate content in B. subtilis knockout mutants showed that (i) there must be one or several still unidentified phosphatases that can replace the deleted proteins; (ii) such replacements, however, cannot fully restore the intracellular content of any of three flavins studied (riboflavin, FMN, FAD); (iii) whereas bacterial fitness was not significantly compromised by mutations, the intracellular balance of flavins and adenylates did show some significant changes.

HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption.

Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 µg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.

Patterns of amino acid conservation in human and animal immunodeficiency viruses.

MOTIVATION: Due to their high genomic variability, RNA viruses and retroviruses present a unique opportunity for detailed study of molecular evolution. Lentiviruses, with HIV being a notable example, are one of the best studied viral groups: hundreds of thousands of sequences are available together with experimentally resolved three-dimensional structures for most viral proteins. In this work, we use these data to study specific patterns of evolution of the viral proteins, and their relationship to protein interactions and immunogenicity. RESULTS: We propose a method for identification of two types of surface residues clusters with abnormal conservation: extremely conserved and extremely variable clusters. We identify them on the surface of proteins from HIV and other animal immunodeficiency viruses. Both types of clusters are overrepresented on the interaction interfaces of viral proteins with other proteins, nucleic acids or low molecular-weight ligands, both in the viral particle and between the virus and its host. In the immunodeficiency viruses, the interaction interfaces are not more conserved than the corresponding proteins on an average, and we show that extremely conserved clusters coincide with protein-protein interaction hotspots, predicted as the residues with the largest energetic contribution to the interaction. Extremely variable clusters have been identified here for the first time. In the HIV-1 envelope protein gp120, they overlap with known antigenic sites. These antigenic sites also contain many residues from extremely conserved clusters, hence representing a unique interacting interface enriched both in extremely conserved and in extremely variable clusters of residues. This observation may have important implication for antiretroviral vaccine development. AVAILABILITY AND IMPLEMENTATION: A Python package is available at https://bioinf.mpi-inf.mpg.de/publications/viral-ppi-pred/ CONTACT: voitenko@mpi-inf.mpg.de or kalinina@mpi-inf.mpg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1.

3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1-infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1.

Analise das campanhas de comunicação sobre o câncer de mama: um estudo comparativo entre as iniciativas do INCA e do IBCC

A informação é uma grande aliada na vida da mulher com câncer de mamam, não apenas para comentar sobre feminilidade, auto-estima e qualquer outra questão de ordem social e psicológica inerente à realidade da doença, mas também para promover a educação sobre o assunto e divulgar o acesso aos direitos relativos à saúde pública feminina. As peças de publicidade sobre câncer de mama ganharam amplo espaço na mídia em geral, o que constitui uma responsabilidade significativa assumida pelos veículos de comunicação e por profissionais da área. Todavia, importa analisar de que maneira as propagandas desenvolvidas incorporam elementos potenciais de transgressões comportamentais, informações que em máximo grau de entendimento poderiam prevenir, curar e diminuir a mortalidade por câncer de mama. A pesquisa analisa as iniciativas publicitárias de controle da doença câncer de mama no Brasil, verificando as suas ocorrências nas diferentes mídias existentes, bem como os discursos adotados no cenário da comunicação de massa, articulando tais assuntos às questões de gênero. Por meio da junção da linha de pesquisa semiótica e de teóricos críticos da comunicação de massa espera-se averiguar o processo de emissão publicitária. Sendo assim, serão contrapostos os conceitos sociológicos da difusão das mensagens com a análise das peças destinadas à mulher para o embasamento da argumentação teórica. Optou-se também pela adoção de autores ligados às áreas sociológicas do câncer de mama e das questões de gênero. Foram consideradas ações publicitárias sobre a doença idealizadas pelo Ministério da Saúde por meio do INCA - Instituto Nacional de Câncer e pelas iniciativas do Instituto Brasileiro de Controle do Câncer - IBCC. Pretende-se verificar com a pesquisa qual é a contribuição das ações comunicativas às perspectivas de melhoria da condição social da mulher, destacando se as peças desenvolvidas mobilizam a sociedade se os efeitos da campanha atingem a sociedade como um todo, influenciando na erradicação e prevenção da doença.

Information is a great ally to a woman who has got breast cancer, not only to tell her about femininity, self-esteem or some social or psychological questions regarding the reality of the disease, but also to provide education about that matter and help her have access to the women's rights related to public health. The publicity pieees about breast caneer have got large space in the overall media, which means great responsibility taken by communication means and professionals. However, it is important to analyze to what extent the pieces contain potential elements for behavior changes and information that could prevent, cure and decrease breast cancer mortality if they were fully understood. The present research analyzes the advertising initiatives concerning the control of breast cancer in Brazil, by checking their occurrences in the different media as well as the speeches adopted for mass communication and the articulation of those matters to gender issues. By joining the semiotic research line and mass communication critical theoreticians, the present work aims at investigating the advertising process. So, the messages sociological concepts will be opposed to the analysis of the pieces towards the women to have the basis for theoretical argumentation. Some authors who deal with social aspects of breast cancer and gender issues will also be referred. The present research focused publicity initiatives about the disease taken by Ministcrio da Sallde through Inca - Instituto Nacional de Cancer and IBCC - Instituto Brasileiro de Controle do Cancer. The research aims at checking if communication actions contribute to the perspective of improving the woman's social condition, i r they help the society become aware of that matter, if the information they provide generate benefits and if the campaigns reach the whole society and influence the erradication and prevention of the disease.