Communication and signal exchange in the Rhizobium bradyrhizobium legume system

A new comprehensive communication concept in the Rhizobium/Bradyrhizobium legume symbiosis was developed. It includes a root zone specific flavonoid exudation, the differential activity of phenylpropane/acetate pathway derivatives on chemotaxis, nod-gene inducing activity and phytoalexin resistance induction on the microsymbiont side (Bradyrhizobium). Nod factor production from the microsymbiont affects the host plant in root hair curling and meristem induction. Phytoalexin production in the host plant is also an early response, however repressed to a low level after a few hours. Another strategy of the microsymbiont to overcome phytoalexin effects is degradation of phytoalexins in Rhizobium leguminosarum bv. vicieae. Competitiveness within the same infection group of the microsymbiont was studied with gus-gene fusion, using the blue coloured nodules to easily discriminate marked strains from unmarked competitors. New exopolysaccharide (EPS) mutants of Bradyrhizobium japonicum were reconstructed homologous with a DNA region to exoB gene of Rhizobium meliloti. Their clearly reduced competitiveness of nodulation, demonstrates that exopolysaccharides of Bradyrhizohium japonicum also have an important function during the early stages of this symbiotic interaction

Movimento pendular e ocupação na Região Metropolitana de Recife - PE

Este artigo expõe o esforço metodológico de construção de categorias ocupacionais para qualificar o movimento pendular na região metropolitana de Recife utilizando dados do Censo Demográfico de 2010 organizados segundo critérios de atividades socioeconômicas e nível de especialização. Os principais resultados apontam para uma concentração do fluxo pendular no centro da região metropolitana e, secundariamente, fluxos em direção ao sul da metrópole, onde importantes investimentos econômicos estão ocorrendo estimulados pela formação do Complexo de Suape. Em relação ao perfil dos ocupados, confirma-se o caráter terciário da metrópole, revelando-se adicionalmente resultados diferenciados no setor Industrial.A partir des données du Census Démographique de 2010 organisés selon les activités économiques et le niveau de spécialisation, on a fait un effort méthodologique de construction de catégories occupationelles afin de qualifier la mobilité pendulaire dans la Région Métropolitaine de Recife (PE). Les résultats principaux indiquent une concentration du flux pendulaire au centre de la région métropolitaine et, en termes secondaires, des flux vers le sud de la métropole (là où des importantes investissements sont stimulés par le Complex de Suape). En ce qui concerne au profil des occupés, on confirme la nature terciaire de la métropole, mais aussi des différents résultats dans le secteur industriel.This article exposes the methodological efforts to create occupation categories in order to classify commuting within the Recife Metropolitan Region, based on Demographic Census 2010 data. The criteria adopted to organize this data were the socio-economic activities and specialization. The main outcomes indicates a concentration of commuting flows at the core of the metropolitan region, and, in a minor degree, there also some southward flows, where important investments have been taking place as a consequence of the construction of the Suape complex. Regarding the occupied profiles, the tertiary function of the metropolis has been confirmed, with some additional results associated with industrial sector.Este artículo presenta un esfuerzo metodológico para realizar una construcción de categorías ocupacionales capaces de cualificar el movimiento pendular de los ocupados en la región metropolitana de Recife. Para ello, son utilizados los datos del Censo de 2010, que están organizados segundo criterios de las actividades socioeconómicas y del nivel de especialización. Los principales flujos ocupacionales estan en el centro de la región metropolitana, en seguida, los flujos hacia el sur de la metropole, donde importantes investimentos económicos han ocurrido, sobre todo, estimulados por la construcción del Complexo de Suape. Con relación al perfil ocupacional, está confirmado la función terciaria de la metropole, agregando resultados diferenciados en el sector industrial

Does Valproic Acid Induce Neuroendocrine Differentiation in Prostate Cancer?

Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatment in vivo. In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expression in vitro in a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevant in vivo setting

A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it>) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.</p> <p>Methods</p> <p>Six patients with advanced RCC and mutated <it>VHL </it>genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.</p> <p>Results</p> <p>Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.</p> <p>Conclusions</p> <p>The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. Trial registration: 98C0139</p

A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D-ligand binding

This is an accepted manuscript of an article published by AAAS in Science Signaling on 30/05/2017, available online: https://stke.sciencemag.org/content/10/481/eaai8904 The accepted version of the publication may differ from the final published version.NKG2D (natural killer group 2, member D) is an activating receptor found on the surface of immune cells, including natural killer (NK) cells, which regulates innate and adaptive immunity through recognition of the stress-induced ligands ULBP1 (UL16 binding protein 1) to ULBP6 and MICA/B. Similar to class I human leukocyte antigen (HLA), these NKG2D ligands have a major histocompatibility complex–like fold and exhibit pronounced polymorphism, which influences human disease susceptibility. However, whereas class I HLA polymorphisms occur predominantly in the α1α2 groove and affect antigen binding, the effects of most NKG2D ligand polymorphisms are unclear. We studied the molecular and functional consequences of the two major alleles of ULBP6, the most polymorphic ULBP gene, which are associated with autoimmunity and relapse after stem cell transplantation. Surface plasmon resonance and crystallography studies revealed that the arginine-to-leucine polymorphism within ULBP0602 affected the NKG2D-ULBP6 interaction by generating an energetic hotspot. This resulted in an NKG2D-ULBP0602 affinity of 15.5 nM, which is 10- to 1000-fold greater than the affinities of other ULBP-NKG2D interactions and limited NKG2D-mediated activation. In addition, soluble ULBP0602 exhibited high-affinity competitive binding for NKG2D and partially suppressed NKG2D-mediated activation of NK cells by other NKG2D ligands. These effects resulted in a decrease in a range of NKG2D-mediated effector functions. Our results reveal that ULBP polymorphisms affect the strength of human lymphocyte responses to cellular stress signals and may offer opportunities for therapeutic intervention.Leukaemia and Lymphoma Researc

Lipoprotein Profiles in Class III Obese Caucasian and African American Women with Nonalcoholic Fatty Liver Disease

Triglyceride content in the liver is regulated by the uptake, production and elimination of lipoproteins, and derangements in these processes contribute to nonalcoholic fatty liver disease (NAFLD). Previous studies show a direct relationship between intrahepatic fat and production of apolipoprotein B100 (apoB100) containing particles, VLDL and LDL, but little consensus exists regarding changes in lipoprotein production in the development of simple steatosis (SS) versus nonalcoholic steatohepatitis (NASH). Further, ethnic variations in lipoproteins among SS and NASH are unknown as is how such variations might contribute to the differential prevalence of disease among Caucasians versus African Americans. In this study, we assessed plasma lipoprotein profiles by nuclear magnetic resonance (NMR) spectroscopy in 70 non-diabetic class III obese females recruited from the surgical weight loss clinic. Of these, 51 females were stratified by biopsy-staged NAFLD severity (histologically normal, SS, or NASH). NASH females displayed increased circulating triglycerides and increased VLDL particle number and size relative to those with histologically normal livers, while total and large LDL concentration decreased in SS versus NASH and correlated with increased insulin resistance (via HOMA2-IR). When Caucasian women were examined alone (n = 41), VLDL and triglycerides increased between normal and SS, while total LDL and apoB100 decreased between SS and NASH along with increased insulin resistance. Compared to Caucasians with SS, African American women with SS displayed reduced triglycerides, VLDL, and small LDL and a more favorable small to large HDL ratio despite having increased BMI and HOMA2-IR. These findings suggest that ApoB100 and lipoprotein subclass particle number and size can delineate steatosis from NASH in obese Caucasian females, but should be interpreted with caution in other ethnicities as African Americans with SS display relatively improved lipoprotein profiles. This may reflect variation in the relationship between dyslipidemia and NAFLD progression across gender and ethnicity

Important performance characteristics in elite clay and grass court tennis match-play.

The performance characteristics of elite tennis match-play differ depending on court surface. However, the performance characteristics (e.g. aces, first serve points won, forced errors) most associated with success on different surfaces are currently unknown. With three weeks typically separating Roland Garros and Wimbledon, the transition from clay to grass courts, whereby players must adapt their game style between surfaces, is crucial to understand. Using the recently validated PWOL method, we analysed 984 singles matches across the 2016 and 2017 Roland Garros and Wimbledon tournaments, to identify the most important performance characteristics in clay and grass court tennis. Results revealed that points won of 0-4 shot rally length, first serve points won and baseline points won were most strongly associated with success for both sexes; serve-related performance characteristics (aces, double faults and average first serve speed) were among the least associated with success. Furthermore, winning short points (points of 0-4 shots) was more closely associated with success than winning medium-length (5-8 shots) and long points (9+ shots). To be representative of match-play, findings suggest that players should afford sufficient practise time to short rallies and point-ending strategies during the clay and grass court seasons, rather than over-emphasising long rallies

The Prospect of using Three-Dimensional Earth Models To Improve Nuclear Explosion Monitoring and Ground Motion Hazard Assessment

The last ten years have brought rapid growth in the development and use of three-dimensional (3D) seismic models of earth structure at crustal, regional and global scales. In order to explore the potential for 3D seismic models to contribute to important societal applications, Lawrence Livermore National Laboratory (LLNL) hosted a 'Workshop on Multi-Resolution 3D Earth Models to Predict Key Observables in Seismic Monitoring and Related Fields' on June 6 and 7, 2007 in Berkeley, California. The workshop brought together academic, government and industry leaders in the research programs developing 3D seismic models and methods for the nuclear explosion monitoring and seismic ground motion hazard communities. The workshop was designed to assess the current state of work in 3D seismology and to discuss a path forward for determining if and how 3D earth models and techniques can be used to achieve measurable increases in our capabilities for monitoring underground nuclear explosions and characterizing seismic ground motion hazards. This paper highlights some of the presentations, issues, and discussions at the workshop and proposes a path by which to begin quantifying the potential contribution of progressively refined 3D seismic models in critical applied arenas

Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas

<p>Abstract</p> <p>Background</p> <p>Gliomas are the most common neoplasm of the brain. High-grade gliomas often resist treatment even with aggressive surgical resection and adjuvant radiation and chemotherapy. Despite the combined treatment, they frequently recur with the same or higher-grade histology. Genetic instability is commonly associated with inactivation of the normal DNA repair function and tumour suppressor genes as well as activation of oncogenes resulting from alterations of promoter hypermethylation, but the molecular mechanisms of the histological and clinical progression of gliomas are still poorly understood.</p> <p>Methods</p> <p>This study involved longitudinal analysis samples of primary and recurrent gliomas to determine whether the progression of low- and high-grade gliomas is associated with the promoter methylation of the DNMT1, MGMT and EGFR genes by PCR-based restriction enzyme assay. Epigenetic inactivation of these three important glioma-associated genes was analyzed in paired biopsy samples from 18 patients with tumour recurrence.</p> <p>Results</p> <p>The methylation analysis of the CpG sites in the DNA methyltransferase (DNMT1) promoter revealed a total of 6 hypermethylations (6/18), the methylguanine-DNA methyltransferase (MGMT) promoter revealed a total of 10 hypermethylations (10/18) and the epithelial grow factor receptor (EGFR) promoter revealed a total of 12 (12/18) hypermethylations respectively in recurrent gliomas. The results demonstrated that DNMT1 promoter hypermethylation does not occur in low-grade gliomas, it was mainly observed in secondary glioblastomas. Additionally, the MGMT and EGFR promoter was hypermethylated in both low-and high-grade GLs and their corresponding histological transformed GLs.</p> <p>Conclusion</p> <p>This study has provided further evidence that the histological transformation and progression of gliomas may be associated with the inactivation of the EGFR and MGMT genes. It seems that EGFR and MGMT promoter hypermethylations are early events in the clonal evolution of gliomas and this gene inactivation has proved to be stable even in tumour recurrence. However, the DNMT hypermethylation is a late part of glioma progression.</p> <p>Virtual slides</p> <p>The virtual slide(s) for this article can be found here: <url>http://www.diagnosticpathology.diagnomx.eu/vs/1935054011612460</url></p