Modelling spatiotemporal gradients of biomolecules on polyethylene glycol hydrogels

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2017, Tutores : Elena Martínez, Gizem AltayThe di usion of the stemness proteins Epidermal grow factor, R-spondin and Noggin (involved in the intestinal epithelial development) within a hydrogel material was simulated using COMSOL Multiphysics software. For the model, similar sized model proteins; Insulin, Carbonic Anhydrase and Bovine Serum Albumin were used. The steady state times and concentrations were determined at the gel surface for a rectangular and a pillar array model. It has been found that geometry was important and had to be implemented in order to better predict the surface concentrations. The gradient obtained along the pillar surface was most evident for BSA (Noggin). We believe that this model can be useful in designing experiments in intestinal epithelial development studies

Next-to-leading-order QCD matching for ∆F = 2 processes in scalar leptoquark models

Leptoquarks provide viable solutions to the flavour anomalies, i.e. they can explain the tensions between the measurements and the Standard Model predictions of the anomalous magnetic moment of the muon as well as b → sℓ+ℓ− and b → cτν processes. However, LQs also contribute to other flavour observables, such as ∆F = 2 processes, at the loop-level. In particular, Bs − B¯¯¯¯s mixing provides a crucial bound in setups addressing b → cτν data, often excluding a big portion of the parameter space that could otherwise account for it. In this article, we first derive the complete leading order matching, including all five scalar LQ representations, for D0 − D¯¯¯¯0, K0 − K¯¯¯¯¯0 and Bs,d − B¯¯¯¯s,d mixing (at the dimension-six level). We then calculate the next-to-leading order αs matching corrections to these ∆F = 2 processes in generic scalar leptoquark models. We find that the two-loop corrections increase the effects in ∆F = 2 processes by ~ 5-10% and significantly reduce the matching scale uncertainty

Modeling Biochemical Gradients In Vitro to Control Cell Compartmentalization in a Microengineered 3D Model of the Intestinal Epithelium

Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how are they sensed by the epithelium is still not fully understood. Here a new in vitro model of the small intestine based on primary epithelial cells (i), apically accessible (ii), with native tissue mechanical properties and controlled mesh size (iii), 3D villus-like architecture (iv), and precisely controlled biomolecular gradients of the ISC niche (v) is presented. Biochemical gradients are formed through hydrogel-based scaffolds by free diffusion from a source to a sink chamber. To confirm the establishment of spatiotemporally controlled gradients, light-sheet fluorescence microscopy and in-silico modeling are employed. The ISC niche biochemical gradients coming from the stroma and applied along the villus axis lead to the in vivo-like compartmentalization of the proliferative and differentiated cells, while changing the composition and concentration of the biochemical factors affects the cellular organization along the villus axis. This novel 3D in vitro intestinal model derived from organoids recapitulates both the villus-like architecture and the gradients of ISC biochemical factors, thus opening the possibility to study in vitro the nature of such gradients and the resulting cellular response.© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH

Parent-child agreement in the health related quality of life (HRQOL) of children with attention-deficit/hyperactivity disorder (ADHD): a longitudinal study

Objetivos: evaluar la concordancia entre padres e hijos sobre los cambios producidos en la calidad de vida relacionada con la salud (CVRS) de niños tratados por trastorno por déficit de atención con hiperactividad (TDAH) durante un corto período de tiempo y comparar las puntuaciones con las normas de referencia de la población general. Métodos: estudio prospectivo en niños de 6 a 12 años con TDAH. Los padres y sus hijos completaron la versión española del CHIP-CE (Child Health and Illness Profile-Child Edition 'Perfil de salud infantil') al iniciar el tratamiento y a las 8 semanas. Las puntuaciones del CHIP-CE de ambas visitas se compararon mediante el test de la t de Student para datos apareados, el tamaño del efecto (TE), los coeficientes de correlación intraclase (CCI) y los diagramas de dispersión. Las evaluaciones de padres e hijos se compararon con las puntuaciones del CHIP-CE de la muestra de referencia española. Resultados: en el análisis se incluyó a 31 niños y a sus padres. El mayor cambio entre la visita inicial y la visita de seguimiento se produjo en la dimensión de riesgos, tanto en los niños como en los padres (TE=0,24 y 0,49, respectivamente). El CCI presentó un intervalo de entre 0,44 (satisfacción) y 0,01 (riesgos). Las puntuaciones de los niños fueron similares a los valores de referencia poblacional. Todas las dimensiones de la versión de padres del CHIP-CE presentaron puntuaciones medias estandarizadas inferiores a los valores de referencia en la visita inicial y fueron próximas a los valores de referencia tras el tratamiento. Conclusiones: el presente estudio mostró poca concordancia entre padres e hijos y sugiere que se deberían recoger ambas perspectivas en futuros estudios del impacto y del tratamiento del TDAH

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

tardis-sn/tardis: TARDIS v2023.11.05

<p>This release has been created automatically by the TARDIS continuous delivery pipeline.</p> <p>A complete list of changes for this release is available at <a href="https://github.com/tardis-sn/tardis/blob/master/CHANGELOG.md">CHANGELOG.md</a>.</p&gt

tardis-sn/tardis: TARDIS v2023.10.20

<p>This release has been created automatically by the TARDIS continuous delivery pipeline.</p> <p>A complete list of changes for this release is available at <a href="https://github.com/tardis-sn/tardis/blob/master/CHANGELOG.md">CHANGELOG.md</a>.</p&gt