Novel Microscopic Mechanism of Intermixing during Growth on Soft Metallic Substrates

Generic computer simulations using empiric interatomic potentials suggest a new, collective mechanism that could be responsible for mixing at heteroepitaxial interfaces. Even if single adsorbate atoms diffuse by hopping on the substrate surface and do not mix at the terraces, two-dimensional islands formed by nucleation may become unstable above a certain critical size and explode upwards forming clusters of several atomic layers. This process is accompanied by strong distortions of the underlying atomic layers, and on soft materials it can result in surface etching and incorporation of substrate atoms into the islands.Fil: Gomez, Liliana Maria. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura; ArgentinaFil: Slutzky, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Ferron, Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: de la Figuera, J.. Sandia National Laboratories; Estados UnidosFil: Camarero, J.. Universidad Autónoma de Madrid; EspañaFil: Vazquez de Parga, A.. Universidad Autónoma de Madrid; EspañaFil: de Miguel, J.J.. Universidad Autónoma de Madrid; EspañaFil: Miranda, R.. Universidad Autónoma de Madrid; Españ

“The ladies are not for turning”: exploring how leader gender and industry sector influence the corporate social responsibility practices of franchise firms

This study of 246 franchise firms in Spain explores differences in Corporate Social Responsibility (CSR) practices as a function of a leader's gender and the industry sector. The results suggest that female-led firms engage more with normative CSR, while male leadership prompts a more instrumental approach. Overall, B2B companies engage more in instrumental CSR, while there are no significant differences between B2B and B2C firms in normative CSR. Interestingly, the results indicate that female-led firms engage more in CSR practices (normative and instrumental) in the B2B sector compared to B2C. Male-led firms, by contrast, tend to do so more in instrumental CSR in the B2C sector, thus operating more instrumentally when the outlook appears more promising. The results challenge existing theories whereby female-led firms may engage more in CSR in the B2C sector as opposed to B2B. The results support theories proposing that female-led firms adopt more of a stewardship theory approach in the B2B sector, building relationships and social capital through activities such as CSR. The findings extend the state-of-the-art on how gender may influence CSR practices in both type (normative or instrumental) and circumstance (B2B or B2C)

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

BACKGROUND In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES The authors aimed to determine the role of the calcineurin splicing variant CnA beta 1 in the context of cardiac hypertrophy and its mechanism of action. METHODS Transgenic mice overexpressing CnAb1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnA beta 1 (CnA beta 1(Delta i12) mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. RESULTS In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnA beta 1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAb1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnA beta 1. CnA beta 1(Delta i12) mice show increased cardiac hypertrophy and declined contractility. CONCLUSIONS The metabolic reprogramming induced by CnAb1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches. (J Am Coll Cardiol 2018; 71: 654-67) (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).This work was supported by grants from the European Union (CardioNeT-ITN-289600 and CardioNext-608027 to Dr. Lara-Pezzi; Meet-ITN-317433 to Dr. Enriquez; UE0/MCA1108 to Dr. Acin-Perez), from the Spanish Ministry of Economy and Competitiveness (SAF2015-65722-R and SAF2012-31451 to Dr. Lara-Pezzi; SAF2015-71521-REDC, BFU2013-50448, and SAF2012-32776 to Dr. Enriquez; RyC-2011-07826 to Dr. Acin-Perez; BIO2012-37926 and BIO2015-67580-P to Dr. Vazquez), from the Spanish Carlos III Institute of Health (CPII14/00027 to Dr. Lara-Pezzi; RD12/0042/066 to Drs. Garcia-Pavia and Lara-Pezzi), from the Regional Government of Madrid (2010-BMD-2321 ``Fibroteam´´ to Dr. Lara-Pezzi; 2011-BMD-2402 ``Mitolab´´ to Dr. Enriquez) and the FIS-ISCIII (PRB2-IPT13/0001 and RD12/0042/0056-RIC-RETICS to Dr. Vazquez). This work was also supported by the Plan Estatal de IthornDthornI 2013-2016-European Regional Development Fund (FEDER) ``A way of making Europe,´´ Spain. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Drs. Vazquez and Garcia-Pavia have served as consultants for VL39. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Padron-Barthe, Villalba-Orero, and Gomez-Salinero contributed equally to this work and are joint first authors. Robyn Shaw, MD, PhD, served as Guest Editor for this paper.S

Estado de México y democracia en los albores del siglo XXI

De acuerdo con su título, este libro, compuesto por seis capítulos y dos anexos, reúne textos relativos a la democracia y al Estado de México, una de las principales entidades federativas de la República Mexicana. La importancia del Estado de México en el contexto nacional es indiscutible: de las 32 entidades que integran el país, es la que tiene más habitantes y electores (el segundo y el tercer lugares en ambos sentidos son ocupados, respectivamente, por el Distrito Federal y Veracruz), en tanto que está en el segundo lugar por el tamaño de su economía (en el primero se ubica el Distrito Federal y en el tercero, Nuevo León)

Mortalidad y recurrencia de la enfermedad tromboembólica venosa en pacientes adultos: cohorte prospectiva

INTRODUCCIÓN: La enfermedad tromboembólica venosa (ETV) es una patología que aumenta con la edad. Objetivo: comparar la sobrevida de los ancianos y los jóvenes con un primer episodio de ETV aguda y sintomática. MATERIALES Y MÉTODOS: Cohorte prospectiva de casos incidentes de ETV incluidos en el Registro Institucional de Enfermedad Tromboembólica venosa (NCT01372514) del Hospital Italiano de Buenos Aires entre 2012-2014, dividido en grupos jóvenes (17-64 años) y ancianos (≥ 65 años). Todos los pacientes fueron seguidos anualmente para evaluar el tiempo a la recurrencia (progresión o nuevo evento sintomático de ETV) como eventos competitivos en contexto de muerte y sangrado mayor. Se presentaron los riesgos crudos (c) y ajustados (a). RESULTADOS: se incluyeron 446 pacientes, el 63% (292) fueron mayores de 65 años. La sobrevida fue menor en los ancianos comparados con los jóvenes (p 0.007), a los 3 meses 87% vs 95% y al año 73% vs 87%, respectivamente. Los ancianos presentaron un HRc1,71 y HR a 1.68. La recurrencia global fue 5% (IC 95% 3-8) al mes, 6% (IC 95% 4-9) a los 3 meses, 8% (IC 95% 6-11) al año y 13% (IC 95% 9-18) a los dos años. No se encontró asociación entre la edad y la recurrencia sub hazard 0.8(IC 0,34-1,86). El sangrado ocurrió en un 9% (39) de los pacientes. CONCLUSIONES: La mortalidad global en pacientes con ETV confirmada es mayor en la población anciana. No hubo diferencias en relación a la recurrencia de ETV, ni el sangrado y tampoco con la edad.INTRODUCTION: Venous thromboembolic disease (VTE) is a pathology that increases with age. OBJECTIVE: to compare the survival of the elderly and the young with a first episode of acute and symptomatic VTE. MATERIALS AND METHODS: Prospective cohort of incident VTE cases included in the Institutional Registry of Venous Thromboembolic Disease (NCT01372514) of the Italian Hospital of Buenos Aires between 2012-2014, divided into young groups (17-64 years old) and elderly (65 years old). All the patients were followed annually to assess the time to recurrence (progression or new symptomatic event of VTE) as competitive events in the context of death and major bleeding. Raw (c) and adjusted (a) risks were presented. RESULTS: 446 patients were included, 63% (292) were older than 65 years. Survival was lower in the elderly compared to the young (p 0.007), at 3 months 87% vs. 95% and at one year 73% vs. 87%, respectively. The elderly had a HRc1.71 and HR at 1.68. The overall recurrence was 5% (95% CI 3-8) at one month, 6% (95% CI 4-9) at 3 months, 8% (95% CI). 6-11) at one year and 13% (95% CI 9-18) at two years. No association was found between age and recurrence sub hazard 0.8 (CI 0.34- 1.86). Bleeding occurred in 9% (39) of the patients. CONCLUSIONS: The overall mortality in patients with confirmed VTE is higher in the elderly population. There were no differences in relation to the recurrence of VTE, or bleeding, and neither with age.INTRODUÇÃO: A doença tromboembólica venosa (TEV) é uma patologia que aumenta com a idade. OBJETIVO: comparar a sobrevida de idosos e jovens com um primeiro episódio de TEV agudo e sintomático. MATERIAIS E MÉTODOS:Coorte prospectiva de casos de TEV incidentes incluídos no Registro Institucional de Doença Tromboembólica Venosa (NCT01372514) do Hospital Italiano de Buenos Aires entre 2012-2014, divididos em grupos jovens (17 a 64 anos) e idosos (65 anos) velho). Todos os pacientes foram acompanhados anualmente para avaliar o tempo de recorrência (progressão ou novo evento sintomático de TEV) como eventos competitivos no contexto de morte e sangramento grave. Os riscos brutos (c) e ajustados (a) foram apresentados. RESULTADOS:446 pacientes foram incluídos, 63% (292) tinham idade superior a 65 anos. A sobrevida foi menor nos idosos em comparação aos jovens (p 0,007), aos 3 meses 87% vs. 95% e aos um ano 73% vs. 87%, respectivamente. Os idosos apresentaram HRc1.71 e FC em 1,68. A recorrência geral foi de 5% (IC95% 3-8) em um mês, 6% (IC95% 4-9) em 3 meses, 8% (IC95%). 6-11) em um ano e 13% (IC95% 9-18) em dois anos. Não foi encontrada associação entre idade e recorrência sub-risco 0,8 (IC 0,34-1,86). Ocorreu sangramento em 9% (39) dos pacientes. CONCLUSÕES: A mortalidade geral em pacientes com TEV confirmado é maior na população idosa. Não houve diferenças em relação à recorrência de TEV ou sangramento e nem com a idade.Fil: Posadas Martinez, Maria Lourdes. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pagotto, Vanina Laura. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Grande Ratti, Maria Florencvia. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Alfie, Veronica. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Andresik, Diego. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Torres Gomez, Felipe. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Giunta, Diego Hernan. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luxardo, Rosario. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Scolnik, Marina. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; ArgentinaFil: Vazquez, Fernando Javier. Hospital Italiano. Departamento de Medicina. Servicio de Clínica Médica; Argentin

Loss of SRSF3 in Cardiomyocytes Leads to Decapping of Contraction-Related mRNAs and Severe Systolic Dysfunction

RATIONALE: RBPs (RNA binding proteins) play critical roles in the cell by regulating mRNA transport, splicing, editing, and stability. The RBP SRSF3 (serine/arginine-rich splicing factor 3) is essential for blastocyst formation and for proper liver development and function. However, its role in the heart has not been explored. OBJECTIVE: To investigate the role of SRSF3 in cardiac function. METHODS AND RESULTS: Cardiac SRSF3 expression was high at mid gestation and decreased during late embryonic development. Mice lacking SRSF3 in the embryonic heart showed impaired cardiomyocyte proliferation and died in utero. In the adult heart, SRSF3 expression was reduced after myocardial infarction, suggesting a possible role in cardiac homeostasis. To determine the role of this RBP in the adult heart, we used an inducible, cardiomyocyte-specific SRSF3 knockout mouse model. After SRSF3 depletion in cardiomyocytes, mice developed severe systolic dysfunction that resulted in death within 8 days. RNA-Seq analysis revealed downregulation of mRNAs encoding sarcomeric and calcium handling proteins. Cardiomyocyte-specific SRSF3 knockout mice also showed evidence of alternative splicing of mTOR (mammalian target of rapamycin) mRNA, generating a shorter protein isoform lacking catalytic activity. This was associated with decreased phosphorylation of 4E-BP1 (eIF4E-binding protein 1), a protein that binds to eIF4E (eukaryotic translation initiation factor 4E) and prevents mRNA decapping. Consequently, we found increased decapping of mRNAs encoding proteins involved in cardiac contraction. Decapping was partially reversed by mTOR activation. CONCLUSIONS: We show that cardiomyocyte-specific loss of SRSF3 expression results in decapping of critical mRNAs involved in cardiac contraction. The molecular mechanism underlying this effect likely involves the generation of a short mTOR isoform by alternative splicing, resulting in reduced 4E-BP1 phosphorylation. The identification of mRNA decapping as a mechanism of systolic heart failure may open the way to the development of urgently needed therapeutic tools.This study was supported by grants from the European Union (CardioNeT-ITN-289600 and CardioNext-ITN-608027 to E.L-P.), from the Spanish Ministerio de Economía y Competitividad (RTI2018-096961-BI00, SAF2015-65722-R and SAF2012-31451 to E.L-P.; BIO2015-67580-P and PGC2018-097019-B-I00 to J.V.), the Spanish Carlos III Institute of Health (CPII14/00027 to E.L-P, RD12/0042/066 to P.G.-P. and E.L-P, and RD12/0042/0056, PRB2-IPT13/0001-ISCIII-SGEFI/FEDER, ProteoRed to J.V.), the Madrid Regional Government (2010-BMD-2321 “Fibroteam” to E.L-P.). This study was also supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (ERDF) “A way of making Europe”, Spain. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia

The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid-droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development

Vejez y vulnerabilidad. Retratos de casos y perfiles de estudio en contextos diversos: grandes regiones, localidades rurales y territorios migrantes

México está inmerso en una acelerada transición demográfica, es el séptimo lugar entre los países con envejecimiento acelerado en Latinoamérica, con 9.7% de adultos mayores de 60 años (CONAPO, 2013). La investigación en nuestro país en torno a los sectores envejecidos tiene ya más de un cuarto de siglo, y ha contribuido al desarrollo de los estudios sobre este grupo de la población bajo las tendencias no sólo locales y regionales, sino también internacionales; respondiendo a las necesidades sociales que se modifican a través de la historia.Desde el área de especialización de cada autor, se pone particular atención en las condiciones de la vida cotidiana y las estrategias que se generan para enfrentar y reducir la vulnerabilidad, así como en los retos que se afrontarán por e l tendiente proceso de envejecimiento de la población, principalmente en los ámbitos socioculturales y de salud.Universidad Autónoma del Estado de Méxic

For Those Who Grew Too Fast

This volume welcomes you amid multiple global epidemics. It welcomes you home, hoping that these words provide visibility, comfort, introspection, and roadmap for pushing boundaries. We know we are tired, we know we are facing uncertainty at every turn, and we know that connection is wearing thin. This collection of words serves as an “I see you,” as an “I am with you,” as an “I love you.” These pieces came together toward end of the Spring 2020, when a group of first-year and transfer students came together to speak their existence. They bring memories and a reminder that together we can construct a culture that builds upon our truth and possibility. Education can be an epicenter of civic imagination, innovative directions in service justice, and above all, radical love. This volume is a testament to this. Welcome to First-Gen Voices Volume Nine: For Those Who Grew Too Fast