Della sopraproduzione : studio di economia sociale / F. Wiede

Della sopraproduzione : studio di economia sociale / F. Wiede Milano : Bignami e C., 1880 45 p. ; 19 cm

Strain-Dependent Differences in Bone Development, Myeloid Hyperplasia, Morbidity and Mortality in Ptpn2-Deficient Mice

Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2ex2−/ex2− mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2−/− mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2ex2−/ex2− mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2−/− (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2−/− (BALB/c) mice were not detected in Ptpn2ex2−/ex2− mice. At 14 days of age, bone development was delayed in Ptpn2−/− (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2ex2−/ex2− mice. Ptpn2ex2−/ex2− mice had defects in erythropoiesis and B cell development as evident in Ptpn2−/− (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2−/− (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2−/− (BALB/c) mice, was delayed in Ptpn2ex2−/ex2− mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2−/− (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2ex2−/ex2− mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent

An interaction map of circulating metabolites, immune gene networks, and their genetic regulation

Background: Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. Results: We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. Conclusions: This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.Peer reviewe

Television pictures of Phobos: first results

In February-March 1989, 37 television images of the Martian satellite Phobos were obtained by the Phobos 2 spacecraft from distances of 200-1100 km. These images provide an important supplement to the TV data from the American Mariner 9 and Viking spacecraft in coverage of t4e surface of Phobos and in resolution in certain regions, in spectral range, and in range of phase angles. They make it possible to refine the figure and topographic and geological maps of the surface of Phobos, its spectral and angular reflective characteristics, the surface composition and texture, and characteristics of the orbital and librational motion

An Indication of Anisotropy in Arrival Directions of Ultra-high-energy Cosmic Rays through Comparison to the Flux Pattern of Extragalactic Gamma-Ray Sources

A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above 20 EeV with zenith angles up to 80 degrees. recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard Fermi-LAT sources (2FHL) and starburst galaxies from a sample that was examined with Fermi-LAT. Flux-limited samples, which include all types of galaxies from the Swift-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0 sigma, the highest value of the test statistic being for energies above 39 EeV. The three alternative models are favored against isotropy with 2.7 sigma-3.2 sigma significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed

Validación de la versión en español de la Escala de remoralización

The Remoralization Scale (RS) was developed in order to measure an individual's state in terms of how the person perceives him or herself in relation to his/her self-concept, self-value, hope, empowerment and positive anticipation. However, there is no data on the psychometric properties of the instrument in a non-clinical population. The aim of this study was to validate a Spanish version of the Remoralization Scale (RS) in a non-clinical sample with a prevention objective and/or the promotion of mental health. The original version of the RS was translated into Spanish and it was applied to a non-clinical sample of 1443 university students in Argentina (18–25 years old). Exploratory and confirmatory factor analyses were performed to study the factorial structure and the validity of the construct. Results suggest that a two factor-model (self-satisfaction and self-concept) results in the best fit for this non-clinical population. The reliability of the total scale and for both sub-scales was moderate to high. Discriminant analysis and contrasting groups analysis showed significant results: the clinical sample and the depression-symptoms sample showed less “remoralization” than the non-clinical sample and a group without depression symptoms, respectively. Results are discussed taking into account previous conceptualizations and studies. In conclusion, the RS was validated for its use in a non-clinical Argentinean population. Regarding its construct validity, a two-factor model with high reliability was obtained.La Escala de Remoralización (RS) fue desarrollada para medir el estado de un individuo en términos de cómo se percibe a sí mismo con relación a su autoconcepto, autovaloración, esperanza, empoderamiento y anticipación positiva. Sin embargo, no hay datos de propiedades psicométricas en la población no clínica. El objetivo de este estudio fue validar una versión española de la RS en una muestra no clínica con un objetivo de prevención y/o promoción de la salud mental. La versión original de la RS fue traducida al español y se aplicó a una muestra no clínica de 1.443 estudiantes universitarios en Argentina (de 18 a 25 años). Se realizaron estudios de análisis factorial exploratorio y confirmatorio para estudiar la estructura factorial y la validez del constructo. Los resultados indican que un modelo de 2 factores (autosatisfacción y autoconcepto) presenta un mejor ajuste para esta población no clínica. La consistencia interna de la escala total y de ambas subescalas fue de moderada a alta. Los análisis discriminantes y análisis de grupos contrastados fueron significativos: la muestra clínica y sujetos con síntomas de depresión mostraron menos «remoralización» que la muestra no clínica y sujetos sin síntomas depresivos. Los resultados se discutieron teniendo en cuenta conceptualizaciones y estudios previos. En conclusión, la RS fue validada para su uso en una población no clínica de Argentina. Respecto a su validez de constructo, se obtuvo un modelo de 2 factores con una alta confiabilidad

PTPN2 regulates T cell lineage commitment and alpha beta versus gamma delta specification

In the thymus, hematopoietic progenitors commit to the T cell lineage and undergo sequential differentiation to generate diverse T cell subsets, including major histocompatibility complex (MHC)-restricted αβ T cell receptor (TCR) T cells and non-MHC-restricted γδ TCR T cells. The factors controlling precursor commitment and their subsequent maturation and specification into αβ TCR versus γδ TCR T cells remain unclear. Here, we show that the tyrosine phosphatase PTPN2 attenuates STAT5 (signal transducer and activator of transcription 5) signaling to regulate T cell lineage commitment and SRC family kinase LCK and STAT5 signaling to regulate αβ TCR versus γδ TCR T cell development. Our findings identify PTPN2 as an important regulator of critical checkpoints that dictate the commitment of multipotent precursors to the T cell lineage and their subsequent maturation into αβ TCR or γδ TCR T cells

Differential regulation of protein tyrosine kinase signalling by Dock and the PTP61F variants

Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signalling pathways in vivo. PTP61Fn effectively repressed the eye overgrowth associated with activation of the epidermal growth factor receptor (EGFR), PTK, or the expression of the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) or insulin receptor (InR) PTKs. PTP61Fn repressed EGFR and PVR-induced mitogen-activated protein kinase signalling and attenuated PVR-induced STAT92E signalling. By contrast, PTP61Fm effectively repressed EGFR- and PVR-, but not InR-induced tissue overgrowth. Importantly, coexpression of Dock with PTP61F allowed for the efficient repression of the InR-induced eye overgrowth, but did not enhance the PTP61Fm-mediated inhibition of EGFR and PVR-induced signalling. Instead, Dock expression increased, and PTP61Fm coexpression further exacerbated the PVR-induced eye overgrowth. These results demonstrate that Dock selectively enhances the PTP61Fm-mediated attenuation of InR signalling and underscores the specificity of PTPs and the importance of adaptor proteins in regulating PTP function in vivo. © 2017 Federation of European Biochemical Societie