Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment.

OBJECTIVES: To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. DESIGN: An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. METHODS: Plasma marker ('analyte') levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. RESULTS: Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. CONCLUSIONS: Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection

Computation of protein geometry and its applications: Packing and function prediction

This chapter discusses geometric models of biomolecules and geometric constructs, including the union of ball model, the weigthed Voronoi diagram, the weighted Delaunay triangulation, and the alpha shapes. These geometric constructs enable fast and analytical computaton of shapes of biomoleculres (including features such as voids and pockets) and metric properties (such as area and volume). The algorithms of Delaunay triangulation, computation of voids and pockets, as well volume/area computation are also described. In addition, applications in packing analysis of protein structures and protein function prediction are also discussed.Comment: 32 pages, 9 figure

Avaliação da incidência de antracnose, do desempenho e estado nutricional de variedades de mangueira, para cultivo orgânico, na região centro-norte do Estado de São Paulo.

A mudança do perfil do consumidor, aliada aos riscos da contaminação por agrotóxicos, tem levado à busca de alternativas ecologicamente apropriadas para produção de frutas. Os objetivos deste trabalho foram avaliar a incidência de antracnose, o desempenho e estado nutricional de variedades de mangueira conduzidas organicamente na região de Pindorama-SP. Foram utilizadas 17 variedades de mangueira. O experimento foi instalado em delineamento experimental em blocos completos ao acaso, com 17 tratamentos (variedades) e seis repetições. Foi avaliada a severidade de antracnose nas folhas, através de uma escala diagramática, atribuindo-se notas aos sintomas. Foram avaliados o crescimento e o desenvolvimento (altura da planta, perímetro do tronco e da copa) e o estado nutricional, mediante análise foliar, das diferentes variedades utilizadas. Através dos resultados obtidos, podem-se considerar como muito suscetíveis à antracnose as variedades Bourbon, Rocha e Rosa; e resistentes, as variedades IAC 111, Alfa, Beta e Parvin; as variedades de manga apresentaram o mesmo padrão de crescimento; as maiores alturas da planta corresponderam aos maiores diâmetros do tronco e da copa; a variedade Parvin apresentou o melhor desempenho dentre as variedades estudadas, com relação à resistência à antracnose, altura e diâmetro do caule e da copa, podendo ser recomendada ao cultivo orgânico. As variedades Omega e Alfa também apresentaram bom crescimento, podendo ser indicadas para esse cultivo, pelo menos nessa fase inicial; as variedades Surpresa e Rosa não apresentaram bom desempenho, no campo, em relação às demais, não devendo ser recomendadas para o cultivo orgânico, principalmente a variedade Rosa, bastante suscetível à antracnose. As concentrações de N, P e K foram elevadas na fase vegetativa das plantas, comparadas à baixa concentração de Ca; houve carência de Boro em todas as variedades estudadas. A manga Rosa, provavelmente, sofreu toxicidade ao excesso de manganês, ocasionando diminuição em seu desenvolvimento

Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment

Contains fulltext : 190926.pdf (publisher's version ) (Open Access)OBJECTIVES: To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level. DESIGN: An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls. METHODS: Plasma marker ('analyte') levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression. RESULTS: Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands. CONCLUSIONS: Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection

Genetic and functional analysis of a set of HIV-1 envelope genes obtained from biological clones with varying syncytium-inducing capacities.

To study HIV-1 envelope-mediated syncytium formation we have amplified, cloned, expressed, and sequenced individual envelope genes from a set of eight biological HIV-1 clones. These clones were obtained from two patients and display either a syncytium-inducing (SI) or nonsyncytium-inducing (NSI) phenotype. Upon expression through recombinant vaccinia virus, individual envelope gene products display heterogeneous syncytium-inducing capacities which reflect the phenotype of the parental biological HIV-1 clones in all cases. For the eight biological HIV-1 clones presented here, variation of the envelope gene alone is sufficient to explain the observed variable syncytium-inducing capacity of the respective parental viruses. In addition we determined the complete nucleotide sequence of these envelope genes. The predicted am

The 2D:4D digit ratio as biomarker for substance abuse

Purpose: The second (2D, index finger) to fourth (4D, ring finger) digit ratio is a biomarker for prenatal testosterone and estrogen exposure. It has been hypothesized that the developmental origins of health and behavior are modulated by the presence or absence of prenatal sex hormones. Several studies have shown a significant relationship between prenatal testosterone concentrations in amniotic fluid and adult risk taking behavior [1]. As the 2D:4D digit ratio does not change after the age of 2, it may be useful as screening tool for later life substance abuse [2]. The purpose of the current study was to investigate the 2D:4D digit ratio and its potential relationship with drug use and smoking. Methods: A survey was held among N= 1067 Dutch adults (57.6% men), aged 16-55 years old (mean age 23.8 years old). For both hands, digit lengths of the second (2D, index finger) and fourth (4D, ring finger) finger were measured using digital vernier calipers recording to 0.01 mm. Measurements were made from the mid-point of the finger crease proximal to the palm to the tip of the finger. Demographics, smoking status (yes/no) and daily number of cigarettes smoked were recorded. Past year's drug use was rated as (1) never, (2) seldom (1-2 times), (3) now and then (3-11 times), monthly, weekly, or daily. Non-parametric correlations were computed to examine the relationship of the 2D:4D digit ratio with alcohol, drug use, and smoking. In addition, substance use of subjects with a hawk-type (2D:4D 1) were compared. Results: Overall, the left 2D:4D digit ratio correlated significantly with frequency of drug use (r = -0.095, p = 0.003). The right 2D:4D digit ratio correlated significantly with the number of cigarettes smoked (r = -0.092, p = 0.005) and the frequency of drug use (r = -0.125, p = 0.0001). For men, the left 2D:4D digit ratio correlated significantly with frequency of drug use (r = -0.125, p = 0.003). The right 2D:4D digit ratio in men correlated significantly with the number of cigarettes smoked (r = -0.127, p = 0.003) and the frequency of drug use (r = -0.141, p = 0.001). For women, none of the correlations between substance abuse and digit ratio were significant. Subjects with a right 2D:4D1. They also significantly more often were drug users (p = 0.004, 33.6% of hawks versus 24.3% of doves). Conclusion: Subjects with a 2D:4D1. Although the strength of the associations is modest, subjects with a lower 2D:4D digit ratio tend to smoke more cigarettes and use drugs of abuse more frequently

DC immunotherapy in HIV-1 infection induces a major blood transcriptome shift

Contains fulltext : 154919.pdf (publisher's version ) (Closed access)OBJECTIVE: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. DESIGN: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. METHODS: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. RESULTS: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. CONCLUSIONS: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies