Simulating Metabolic Processes Using an Architecture Based on Networks of Bio-inspired Processors.

In this work, we propose the Networks of Evolutionary Processors (NEP) [2] as a computational model to solve problems related with biological phenomena. In our first approximation, we simulate biological processes related with cellular signaling and their implications in the metabolism, by using an architecture based on NEP (NEP architecture) and their specializations: Networks of Polarized Evolutionary Processors (NPEP) [1] and NEP Transducers (NEPT) [3]. In particular, we use this architecture to simulate the interplay between cellular processes related with the metabolism as the Krebs cycle and the malate-aspartate shuttle pathway (MAS) both being altered by signaling by calcium

The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study

BACKGROUND: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. METHODS: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). RESULTS: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP's association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). CONCLUSIONS: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.This work has been supported by grants given by Instituto de Salud Carlos III (ISCIII) (grant numbers PI14CIII/00011 and PI17CIII/00003 to SR). AFR is also supported by ISCIII (grant numbers CP14CIII/00010).S

Congreso online: nueva herramienta para fomentar el aprendizaje

Los congresos científicos son una herramienta valiosa en el aprendizaje para estudiantes de tercer ciclo. Sin embargo, no son aprovechados al máximo con esta finalidad, puesto que las intervenciones por parte de los estudiantes, en cuanto a plantear cuestiones se refiere, son prácticamente nulas. Con el objetivo de fomentar la participación de los estudiantes de tercer ciclo en los congresos científicos, se presenta una propuesta de congreso online para estudiantes de doctorado en el programa interuniversitario `Electroquímica. Ciencia y Tecnología`, empleando la herramienta Moodle. Este congreso consiste en dar a conocer, de forma visible y con formato de pósters, comunicaciones científicas de los estudiantes, quienes deben hacer preguntas acerca de las mismas y responder a las realizadas sobre su contribución. Además, y siempre con la finalidad de fomentar la participación en forma de preguntas y discusiones científicas, se otorgarán premios tales como al estudiante más participativo y al mejor póster, para lo que se evaluará la defensa del póster por parte del estudiante

Prácticas de Topografía con el Observatorio Robotizado Montegancedo

En el programa formativo del actual Ingeniero Técnico en Topografía está presente la Astronomía Geodésica o de Posición con el fin de que el futuro profesional conozca los elementos de astronomía necesarios para poder calcular coordenadas latitud y longitud de puntos sobre la superficie terrestre, así como el acimut de direcciones a otros puntos a partir de observaciones a las estrellas. Aunque los métodos astronómicos se van sustituyendo por los métodos por observaciones a satélites (GNSS), ciertos conocimientos astronómicos son necesarios para poder comprender tanto los sistemas de referencias celestes y terrestres, como las observaciones geodésicas y geofísicas. Dentro de este programa formativo juegan un papel fundamental la realización de prácticas en las que el alumno vea y desarrolle sus habilidades para calcular parámetros astronómicos, resultado de su propia observación. En la ETSI de Topografía se viene realizando prácticas de observación a la estrella polar, con el fin de calcular el acimut de una dirección. También observaciones al Sol con el mismo objetivo. La utilización de equipos ópticos clásicos en esta observación entraña cierto riesgo al colocar el ojo sobre el ocular cuando se tiene enfocado el Sol. En prevención de fatales accidentes estas observaciones al Sol fueron retiradas del programa formativo. Recientemente, y gracias a la utilización de un telescopio robotizado, el observatorio Montegancedo (http://om.fi.upm.es), y con registro de imágenes, se ha podido rescatar este tipo de prácticas de observaciones al Sol en la formación de los ingenieros técnicos topográficos (ITT) de la Escuela. Se muestran en este artículo los objetivos perseguidos en esta experiencia, los métodos y materiales utilizados para la misma así como una serie de impresiones finales que se han encontrado en la realización de estas experiencias prácticas

El desarrollo municipal, factor estratégico en el posicionamiento de México en los escenarios políticos y sociales del siglo XXI

LA DEMOCRACIA COMO GOBERNABILIDAD IMPLICA, EN UN PRIMER MOMENTO, establecer una revisión periódica del papel interventor del Estado, por ser éste el principal factor de estabilidad y desarrollo democrático. En un segundo punto, de forma simultánea al estudio del papel del Estado en la conformación de un ambiente de estabilidad, crecimiento, desarrollo, orden y gobernabilidad, merece especial atención el papel y funciones cumplidas tradicionalmente por sus ámbitos de gobierno, como instancias que son fundamentales para la transición, democratización, liberalización y para la propia gobernabilidad

Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptor

PURPOSE: A subgroup of HER2 overexpressing breast tumors co-expresses p95HER2, a truncated HER2 receptor that retains a highly functional HER2 kinase domain but lacks the extracellular domain and results in intrinsic trastuzumab resistance. We hypothesized that lapatinib, a HER2 tyrosine kinase inhibitor, would be active in these tumors. We have studied the correlation between p95HER2 expression and response to lapatinib, both in preclinical models and in the clinical setting EXPERIMENTAL DESIGN: Two different p95HER2 animal models were used for preclinical studies. Expression of p95HER2 was analyzed in HER2 overexpressing breast primary tumors from a first line lapatinib monotherapy study (EGF20009) and a second line lapatinib in combination with capecitabine study (EGF100151). p95HER2 expression was correlated with overall response rate (complete + partial response), clinical benefit rate (complete response + partial response + stable disease ≥ 24 weeks) and progression-free survival using logistic regression and Cox-proportional hazard models. RESULTS: Lapatinib inhibited tumor growth and HER2 downstream signaling of p95HER2 expressing tumors. A total of 68 and 156 tumors from studies EGF20009 and EGF100151 were evaluable, respectively, for p95HER2 detection. The percentage of p95HER2 positive patients was 20.5% in the EGF20009 study and 28.5% in the EGF100151 study. In both studies there was no statistically significant difference in progression-free survival, clinical benefit rate and overall response rate between p95HER2-positive and p95HER2-negative tumors. CONCLUSIONS: Lapatinib as a monotherapy or in combination with capecitabine appears to be equally effective in patients with p95HER2-positive and p95HER2-negative HER2-positive breast tumors

Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.

INTRODUCTION The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease. METHODS We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells. RESULTS Exposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines. CONCLUSION We have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.This work was supported by grants from Ministerio de Ciencia e Innovación (MCIN) from Spain [SAF2016-78711R and PID202-11794 to EM-N and FJC]; Comunidad de Madrid [B2017/BMD-3727 to EMN and FJC]; Comunidad de Madrid (REACT-UE, ANTICIPA-CM Ref. PR38/21-24) to E.M-N and HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679 to FJC the European Union’s Horizon 2020 research and innovation program [ERC-2016- Consolidator Grant 725091 to DS]; MCIN/AEI/10.13039/ 501100011033 [PID2019-108157RB to DS]; la Caixa Foundation (ID 100010434) [LCF/BQ/PR20/11770008 to SW]; Instituto de Salud Carlos III (ISCIII) [PI18/00348 to VE]; ISCIII [PI21/01641 to RT-R]; Spanish National Research and Development Plan, ISCIII and FEDER [PI17/02303 and PI20/01837 to SR-P]; Proyecto Desarrollo Tecnológico [DTS19/00111 to SR-P], AEI/MICIU EXPLORA Project [BIO2017-91272-EXP to SR-P]; Programa Estratégico Instituto de Biologıa y Gene ́ ́ tica Molecular (IBGM), Junta de Castilla y León (CCVC8485) [PID2019-104218RB-I00 to DB]; NIH [DK088199 to RB] and Universidad Complutense de Madrid (UCM 920631) [CT42/ 18-CT43/18 and EB15/21 to BM-A].S

Response trajectories of gambling severity after cognitive behavioral therapy in young-adult pathological gamblers

Background and aims: the significant increase in the prevalence of gambling disorder (GD) among young adults in recent years has attracted interest in determining therapeutic efficiency in this sector of the population. The aim of this work was to estimate the response trajectories of gambling severity during the six-month follow-up after a cognitive behavioral therapy (CBT) program in young adult patients and to identify the main variables associated with each trajectory. Methods: the sample included n = 192 patients, aged 19-35 years old, seeking treatment for GD. Response trajectories were identified through latent class growth analysis. Results: three trajectories emerged: T1 (n = 118, 61.5%), composed of patients with severe GD at pre-treatment and good evolution to recovery; T2 (n = 62, 32.3%), with patients with moderate-high GD affectation at baseline and good evolution to recovery; and T3 (n = 12, 6.3%), with participants with severe baseline GD severity and poor evolution after CBT (Abbott, 2019). The highest risk of poor therapeutic outcomes was related to lower social index positions, high emotional distress, high scores in harm avoidance and low scores in self-directedness. Discussion and conclusions: differences in the response trajectories at short-term follow-up after CBT reveal heterogeneity in the samples including young and young-adult GD patients. Patients' phenotype at baseline should be considered when developing efficient, person-centered intervention programs, which should comprise strategies aimed at increasing emotional regulation capacities, self-esteem and self-efficacy, with the aim of avoiding relapses in the medium-long term after therapy

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk

The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. Methods: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. Results: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). Conclusions: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed