Abrogation of HMX1 function causes rare oculoauricular syndrome associated with congenital cataract, anterior segment dysgenesis, and retinal dystrophy.

PURPOSE: To define the phenotypic manifestation, confirm the genetic basis, and delineate the pathogenic mechanisms underlying an oculoauricular syndrome (OAS). METHODS: Two individuals from a consanguineous family underwent comprehensive clinical phenotyping and electrodiagnostic testing (EDT). Genome-wide microarray analysis and Sanger sequencing of the candidate gene were used to identify the likely causal variant. Protein modelling, Western blotting, and dual luciferase assays were used to assess the pathogenic effect of the variant in vitro. RESULTS: Complex developmental ocular abnormalities of congenital cataract, anterior segment dysgenesis, iris coloboma, early-onset retinal dystrophy, and abnormal external ear cartilage presented in the affected family members. Genetic analyses identified a homozygous c.650A>C; p.(Gln217Pro) missense mutation within the highly conserved homeodomain of the H6 family homeobox 1 (HMX1) gene. Protein modelling predicts that the variant may have a detrimental effect on protein folding and/or stability. In vitro analyses were able to demonstrate that the mutation has no effect on protein expression but adversely alters function. CONCLUSIONS: Oculoauricular syndrome is an autosomal recessive condition that has a profound effect on the development of the external ear, anterior segment, and retina, leading to significant visual loss at an early age. This study has delineated the phenotype and confirmed HMX1 as the gene causative of OAS, enabling the description of only the second family with the condition. HMX1 is a key player in ocular development, possibly in both the pathway responsible for lens and retina development, and via the gene network integral to optic fissure closure.

La (De)construcció de la masculinitat en el teatre de David Mamet

La reflexió efectuada per la teoria contemporania sobre la representació del genere es materialitza d'una manera privilegiada en el teatre. Esta clar que la perforrnativitat intrinseca del fenomen teatral és un espai idoni per qüestionar la construcció de la representació generica. No hi ha dubte que I'especificitat comunicativa del teatre es troba en la «fisicalitat)): I'element corporal té una importancia clau, ja síguí per la presencia física de I'equip actoral i del públic i per la condició efímera (el fet que cap representació no és igual a cap altra). Judith Butler ha escrit sobre el fet que els actes que constitueixen el genere tenen un paral.lelisrne en les actes performatius dels contextos teatrals. La identitat de genere no és una identitat completa, sinó que és una identitat que es construeix, una realització performativa en la qual creiern, i que representem corn si fos una creenca, com si fos una qüestió de fe. Per tant, les possibilitats de transformació del genere es troben en la relació arbitraria d'aquests actes i en la possibilitat d'un altre tipus de repetició (Butler, 1990: 33). L'obra del dramaturg, director, guionista i assagista nord-america David Marnet pot considerar-se una reflexió sobre la construcció de la masculinitat i, de retruc, de les tensions i reptes a que la masculinitat es troba sotmesa en el tornbant de segle. 1. ES

Cationic and charge segregation in La2/3Ca1/3MnO3 thin films grown on (001) and (110) SrTiO3.

Electron energy-loss spectroscopy is used to map composition and electronic states in epitaxial La2/3Ca1/3MnO3 films grown on SrTiO3 001 and 110 substrates. It is found that in partially relaxed 110 films cationic composition and valence state of Mn3+/4+ ions are preserved across the film thickness. In contrast, in fully strained 001 films, the Ca/La ratio gradually changes across the film, being La rich at film/substrate interface and La depleted at free surface; Mn valence state changes accordingly. These observations suggest that a strongly orientation-dependent adaptative composition mechanism dominates stress accommodation in manganite films and provides microscopic understanding of their dissimilar magnetic properties.

Archiving Primary Data: Solutions for Long-Term Studies.

The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (Pls) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.

Retinoblastoma Protein Knockdown Favors Oxidative Metabolism and Glucose and Fatty Acid Disposal in Muscle Cells.

Deficiency in the retinoblastoma protein (Rb) favors leanness and a healthy metabolic profile in mice largely attributed to activation of oxidative metabolism in white and brown adipose tissues. Less is known about Rb modulation of skeletal muscle metabolism. This was studied here by transiently knocking down Rb expression in differentiated C2C12 myotubes using small interfering RNAs. Compared with control cells transfected with non-targeting RNAs, myotubes silenced for Rb (by 80-90%) had increased expression of genes related to fatty acid uptake and oxidation such as Cd36 and Cpt1b (by 61% and 42%, respectively), increased Mitofusin 2 protein content (∼2.5-fold increase), increased mitochondrial to nuclear DNA ratio (by 48%), increased oxygen consumption (by 65%) and decreased intracellular lipid accumulation. Rb silenced myotubes also displayed up-regulated levels of glucose transporter type 4 expression (∼5-fold increase), increased basal glucose uptake, and enhanced insulin-induced Akt phosphorylation. Interestingly, exercise in mice led to increased Rb phosphorylation (inactivation) in skeletal muscle as evidenced by immunohistochemistry analysis. In conclusion, the silencing of Rb enhances mitochondrial oxidative metabolism and fatty acid and glucose disposal in skeletal myotubes, and changes in Rb status may contribute to muscle physiological adaptation to exercise. J. Cell. Physiol. 231: 708-718, 2016. © 2015 Wiley Periodicals, Inc.

E2F1 mediates sustained lipogenesis and contributes to hepatic steatosis.

E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis, and differentiation. Here, we reveal that E2F1 plays an essential role in liver physiopathology through the regulation of glycolysis and lipogenesis. We demonstrate that E2F1 deficiency leads to a decrease in glycolysis and de novo synthesis of fatty acids in hepatocytes. We further demonstrate that E2F1 directly binds to the promoters of key lipogenic genes, including Fasn, but does not bind directly to genes encoding glycolysis pathway components, suggesting an indirect effect. In murine models, E2F1 expression and activity increased in response to feeding and upon insulin stimulation through canonical activation of the CDK4/pRB pathway. Moreover, E2F1 expression was increased in liver biopsies from obese, glucose-intolerant humans compared with biopsies from lean subjects. Finally, E2f1 deletion completely abrogated hepatic steatosis in different murine models of nonalcoholic fatty liver disease (NAFLD). In conclusion, our data demonstrate that E2F1 regulates lipid synthesis and glycolysis and thus contributes to the development of liver pathology.

Les conductes indisciplinades a les classes d'educació física de l'E.S.O. del Col·legi sant Antoni Abat

Aquest treball té tres objectius. El primer, conèixer el concepte de les conductes indisciplinades i les seves diferents tipologies existents a les classes d’Educació Física mitjançant una gran recerca bibliogràfica. Com a segon objectiu, esbrinar quines són les conductes indisciplinades més freqüents dels alumnes de 1r d’E.S.O A i C del Col·legi Sant Antoni Abat dins d’aquesta matèria mitjançant la utilització d’un instrument observacional per a la recollida de dades. I com a últim objectiu, descobrir les habilitats i actituds que ha de portar a terme el professor d’Educació Física per a reduir el nombre de conductes indisciplinades fent una altra recerca bibliogràfica. Aquesta ens possibilitarà la creació d’un instrument observacional dirigit als dos professors d’Educació Física amb la finalitat de saber si aquests les compleixen. Finalment, a partir dels resultats obtinguts dels dos instruments observacionals, tant dels alumnes com dels professors, compararem els resultats entre les classes del professor A i el professor B, els quals ens ajudaran a establir relacions per a respondre a la nostra hipòtesi del treball: Si els professors d’educació física porten a terme certes habilitats i actituds, llavors disminuiran el nombre de conductes indisciplinades.

Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner.

Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment. Rictor deficiency favors memory formation and increases IL-2 secretion capacity without dampening effector functions. Moreover, mTORC2-deficient memory T cells mount more potent recall responses. Enhanced memory formation in the absence of mTORC2 was associated with Eomes and Tcf-1 upregulation, repression of T-bet, enhanced mitochondrial spare respiratory capacity, and fatty acid oxidation. This transcriptional and metabolic reprogramming is mainly driven by nuclear stabilization of Foxo1. Silencing of Foxo1 reversed the increased MPEC differentiation and IL-2 production and led to an impaired recall response of Rictor KO memory T cells. Therefore, mTORC2 is a critical regulator of CD8 T cell differentiation and may be an important target for immunotherapy interventions.

CDK4 is an essential insulin effector in adipocytes.

Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.

Programa SIMBENFISC v1.0. Simulador de beneficis fiscals de la Generalitat de Catalunya.

SIMBENFISC v1.0 permet simular els beneficis fiscals que generen els següents impostos: Successions, Donacions, Transmissions Patrimonials, Actes Jurídics i Operacions Societàries. Genera un informe per a cada impost que conté: 1- Els resultats de la recaptació real per a la liquidació de l’impost segons la normativa vigent a Catalunya i la normativa vigent a l’estat. 2- Els resultats dels beneficis fiscals que corresponen a l’execució de les diferents reduccions i/o deduccions contemplades a cada impost. 3- Els resultats de la projecció de recaptació i dels beneficis fiscals que s’obtindrien d’aplicar determinats supòsits de creixement a) de la base imposable, b) de les liquidacions i c) de canvis de normativa. La informació que processa aquest simulador, òbviament, és específica de cada impost, però el seu ventall es situa aproximadament entre els 50.000 i 300.000 registres. Aquesta informació és l’input del microsimulador i la proporciona la Direcció General de Tributs i Jocs, del Departament d’Economia i Coneixement de la Generalitat de Catalunya, a partir de les autoliquidacions que s’efectuen en cada exercici fiscal anual.

Emprego de catalisadores à base de níquel para homo- e copolimerização de estireno

This review deals with the homo- and copolymerization of styrene with nickel catalysts. The catalytic activity, polymer stereoregularity, polymer molecular weight and polydispersity are dependent upon nickel ligands and reaction parameters. Catalysts supported on silica, treated with methylaluminoxane (MAO), have shown higher stereospecificity and activity compared to homogeneous ones. The influence of these parameters is discussed focusing on the elucidation of some aspects of the polymerization mechanism.

De principiis actionum moralium

Invocatio: J.N.D.N.I.C.

Specimen computandi triduanam Christi in sepulcro commorationem

Invocatio: I.N.I.C.

Influence of initial CaO/SiO2 ratio on the hydration of rice husk ash-Ca(OH)2 and sugar cane bagasse ash-Ca(OH)2 pastes

This work presents the results of a study on the hydration of pastes containing calcium hydroxide and either rice husk ash (RHA) or sugar cane bagasse ash (SCBA) in various initial CaO/SiO2 molar ratios. The products of the reactions were characterized by thermal analyses X-ray diffraction, and scanning electron microscopy. In the case of the RHA pastes, the product was composed of CaO-SiO2-H2O (type I C-S-H) or CaO-SiO2-H2O (type II C-S-H) according to the CaO/SiO2 ratio of the mixture. In contrast, in the case of the SBCA pastes, the product was composed primarily of CaO-SiO2-H2O that differed from both the previous types; the product also contained inclusions of calcium aluminate hydrates.