Ovarian cancer G protein-coupled receptor 1 deficiency exacerbates crystal deposition and kidney injury in oxalate nephropathy in female mice

Ovarian cancer G protein-coupled receptor 1 (OGR1) (Gpr68) and G protein-coupled receptor 4 (GPR4) (Gpr4) are proton-activated G protein-coupled receptors that are stimulated upon increased extracellular acidity. These receptors have various physiological and pathophysiological roles in renal acid–base physiology, tissue inflammation, and fibrosis among others. Their function in injured renal tissue, however, remains mostly unclear. To address this, we investigated their role in crystalline nephropathy by increasing the oxalate intake of GPR4 KO and OGR1 KO mice. After 10 days of high-oxalate intake and 4 days of recovery, renal crystal content, histopathology, filtration function, and inflammation were assessed. While GPR4 deficiency did not show major alterations in disease progression, OGR1 KO mice had higher urinary calcium levels and exacerbated crystal accumulation accompanied by decreased creatinine clearance and urea excretion and a decreased presence of regulatory T (Treg) cells in kidney tissue. When lowering the severity of the kidney injury, OGR1 KO mice were more prone to develop crystalline nephropathy. In this setting, OGR1 KO mice displayed an increased activation of the immune system and a higher production of proinflammatory cytokines by T cells and macrophages. Taken together, in the acute setting of oxalate-induced nephropathy, the lack of the proton-activated G protein-coupled receptor (GPCR) GPR4 does not influence disease. OGR1 deficiency, however, increases crystal deposition leading to impaired kidney function. Thus, OGR1 may be important to limit kidney crystal deposition, which might subsequently be relevant for the pathophysiology of oxalate kidney stones or other crystallopathies

Blueberry Supply Chain in Italy: Management,Innovation and Sustainability

The growing trend market of fresh products is driven by a consumer oriented to new lifestyles and environmental issues. The berries market in Europe represents a good example of a consumer driven supply chain, due to the capacity to answer all the sequences of the system. To explore the process developed by fruit growers’ associated groups in Italy, the research is organized into four stages. The first stage provides a review of the organization of the fresh fruit supply chain (FFSC) and the need to innovate it in light of the driven demand. The second section focuses on the innovation displayed towards storing, managing and maintaining the quality of fruit during the supply. The third section considers the case study. The manuscript concludes by summarising the main results and discussing the implications for future research. The use of a modified active packaging system (MAP) with “green” films has enabled the maintenance of the quality of the fruits for two months, as well as the presence of the company blueberries market for longer periods, and has finally led to improving the exports, thus reaching new European countries, increasing the turnover of the associated group and better remuneration for the fruit growers as a consequence

Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway

Over 10 million people every year become infected by Treponema pallidum and develop syphilis, a disease with broad symptomatology that, due to the difficulty to eradicate the pathogen from the highly vascularized secondary sites of infection, is still treated with injections of penicillin. Unlike most other bacterial pathogens, T. pallidum infection produces indeed a strong angiogenic response whose mechanism of activation, however, remains unknown. Here, we report that one of the major antigen of T. pallidum, the TpF1 protein, has growth factor-like activity on primary cultures of human endothelial cells and activates specific T cells able to promote tissue factor production. The growth factor-like activity is mediated by the secretion of IL-8 but not of VEGF, two known angiogenic factors. The pathogen's factor signals IL-8 secretion through the activation of the CREB/NF-\u3baB signalling pathway. These findings are recapitulated in an animal model, zebrafish, where we observed that TpF1 injection stimulates angiogenesis and IL-8, but not VEGF, secretion. This study suggests that the angiogenic response observed during secondary syphilis is triggered by TpF1 and that pharmacological therapies directed to inhibit IL-8 response in patients should be explored to treat this disease

Jet-Powered Molecular Hydrogen Emission from Radio Galaxies

H2 pure-rotational emission lines are detected from warm (100-1500 K) molecular gas in 17/55 (31% of) radio galaxies at redshift z<0.22 observed with the Spitzer IR Spectrograph. The summed H2 0-0 S(0)-S(3) line luminosities are L(H2)=7E38-2E42 erg/s, yielding warm H2 masses up to 2E10 Msun. These radio galaxies, of both FR radio morphological types, help to firmly establish the new class of radio-selected molecular hydrogen emission galaxies (radio MOHEGs). MOHEGs have extremely large H2 to 7.7 micron PAH emission ratios: L(H2)/L(PAH7.7) = 0.04-4, up to a factor 300 greater than the median value for normal star-forming galaxies. In spite of large H2 masses, MOHEGs appear to be inefficient at forming stars, perhaps because the molecular gas is kinematically unsettled and turbulent. Low-luminosity mid-IR continuum emission together with low-ionization emission line spectra indicate low-luminosity AGNs in all but 3 radio MOHEGs. The AGN X-ray emission measured with Chandra is not luminous enough to power the H2 emission from MOHEGs. Nearly all radio MOHEGs belong to clusters or close pairs, including 4 cool core clusters (Perseus, Hydra, A 2052, and A 2199). We suggest that the H2 in radio MOHEGs is delivered in galaxy collisions or cooling flows, then heated by radio jet feedback in the form of kinetic energy dissipation by shocks or cosmic rays.Comment: ApJ in press, 40 pages, 18 figures, 14 table

Qualidade de vida de pacientes mastectomizadas: uma revisão integrativa

A mama é um órgão que possui fundamental importância no corpo feminino, tanto para função reprodutora, quanto na imagem que a mulher tem de si mesma. Estudos relatam que a perda da mama gera dificuldades de adaptação a realidade e de imagem corporal, além de dificuldades físicas. O objetivo do estudo trata-se de verificar alterações de qualidade de vida em pacientes submetidas à mastectomia devido ao câncer de mama e possíveis intervenções para melhoria desta qualidade de vida. Trata-se de uma revisão integrativa onde foram selecionados&nbsp;&nbsp; 15 artigos por busca ativa nas bases de dados “PUBMED”, “SCIELO”, “LILACS”, “LATINDEX”. Como critério de busca como usados os seguintes unitermos: “qualidade de vida”; “mastectomizadas”. A presente pesquisa demonstrou que em todos os artigos analisados havia um prejuízo na qualidade de vida e sexualidade de pacientes submetidas à mastectomia. Observou-se, também, que a qualidade de vida melhorava quando a mobilidade daquela paciente era maior e a mesma podia exercer suas funções diárias, no trabalho e domésticas. Outrossim, os piores escores encontrados pelos estudos na qualidade de vidas de pacientes mastectomizadas foram: emocional e físico. Outro fator observado foi que pacientes submetidas à reconstrução mamária apresentaram melhor qualidade de vida, devido ao fator autoestima, autoimagem, prazer com o próprio corpo e com as vestimentas. Além disso, verificou-se que a fisioterapia pode ser um grande fator aliado para melhora da mobilidade, do edema e da função motora em geral, contribuindo para incremento no escore de aptidão física destas pacientes

Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study

<p>Abstract</p> <p>Background</p> <p>Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.</p> <p>Methods</p> <p>Ninety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.</p> <p>Results</p> <p>Results suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.</p> <p>Conclusion</p> <p>Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.</p

Plasticity of BRCA2 Function in Homologous Recombination: Genetic Interactions of the PALB2 and DNA Binding Domains

The breast cancer suppressor BRCA2 is essential for the maintenance of genomic integrity in mammalian cells through its role in DNA repair by homologous recombination (HR). Human BRCA2 is 3,418 amino acids and is comprised of multiple domains that interact with the RAD51 recombinase and other proteins as well as with DNA. To gain insight into the cellular function of BRCA2 in HR, we created fusions consisting of various BRCA2 domains and also introduced mutations into these domains to disrupt specific protein and DNA interactions. We find that a BRCA2 fusion peptide deleted for the DNA binding domain and active in HR is completely dependent on interaction with the PALB2 tumor suppressor for activity. Conversely, a BRCA2 fusion peptide deleted for the PALB2 binding domain is dependent on an intact DNA binding domain, providing a role for this conserved domain in vivo; mutagenesis suggests that both single-stranded and double-stranded DNA binding activities in the DNA binding domain are required for its activity. Given that PALB2 itself binds DNA, these results suggest alternative mechanisms to deliver RAD51 to DNA. In addition, the BRCA2 C terminus contains both RAD51-dependent and -independent activities which are essential to HR in some contexts. Finally, binding the small peptide DSS1 is essential for activity when its binding domain is present, but not when it is absent. Our results reveal functional redundancy within the BRCA2 protein and emphasize the plasticity of this large protein built for optimal HR function in mammalian cells. The occurrence of disease-causing mutations throughout BRCA2 suggests sub-optimal HR from a variety of domain modulations

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2, which is now completed, measured medium-resolution (R=1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa