Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype

Ih Current Is Necessary to Maintain Normal Dopamine Fluctuations and Sleep Consolidation in Drosophila

HCN channels are becoming pharmacological targets mainly in cardiac diseases. But apart from their well-known role in heart pacemaking, these channels are widely expressed in the nervous system where they contribute to the neuron firing pattern. Consequently, abolishing Ih current might have detrimental consequences in a big repertoire of behavioral traits. Several studies in mammals have identified the Ih current as an important determinant of the firing activity of dopaminergic neurons, and recent evidences link alterations in this current to various dopamine-related disorders. We used the model organism Drosophila melanogaster to investigate how lack of Ih current affects dopamine levels and the behavioral consequences in the sleep∶activity pattern. Unlike mammals, in Drosophila there is only one gene encoding HCN channels. We generated a deficiency of the DmIh core gene region and measured, by HPLC, levels of dopamine. Our data demonstrate daily variations of dopamine in wild-type fly heads. Lack of Ih current dramatically alters dopamine pattern, but different mechanisms seem to operate during light and dark conditions. Behaviorally, DmIh mutant flies display alterations in the rest∶activity pattern, and altered circadian rhythms. Our data strongly suggest that Ih current is necessary to prevent dopamine overproduction at dark, while light input allows cycling of dopamine in an Ih current dependent manner. Moreover, lack of Ih current results in behavioral defects that are consistent with altered dopamine levels

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo.

BACKGROUND: Several studies found a benefit of long-chain polyunsaturated fatty acid (LCP) supplementation for visual or mental development, but others found no benefit. Likely contributors to differences among studies are the amount of LCP supplementation, functional outcomes, and sample size. OBJECTIVE: We evaluated LCP supplementation in amounts typical for human milk (based on local and worldwide surveys) in a large cohort of infants by using sweep visual evoked potential (VEP) acuity as the functional outcome. DESIGN: The study was a double-masked, randomized, controlled clinical trial in 103 term infants. By age 5 d, infants were randomly assigned to receive either formula with no docosahexaenoic acid (DHA) or arachidonic acid (ARA) or formula supplemented with DHA and ARA as 0.36% and 0.72%, respectively, of total fatty acids. Sweep VEP acuity was the primary outcome. Random dot stereoacuity, blood lipid profile, growth, and tolerance were secondary outcomes. RESULTS: VEP acuity in the LCP-supplemented group was significantly better than that in the control group at ages 6, 17, 26, and 52 wk. Stereoacuity in the LCP-supplemented group was significantly better than that in the control group at age 17 wk but not at ages 39 and 52 wk. By ages 17 and 39 wk, the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple, respectively, that in the control group. Growth of infants fed LCP-supplemented and control formulas did not differ significantly, and both diets were well tolerated. CONCLUSION: LCP supplementation of term infant formula during the first year of life yields clear differences in visual function and in total red blood cell lipid composition

A randomized controlled trial of long-chain polyunsaturated fatty acid supplementation of formula in term infants after weaning at 6 wk of age.

BACKGROUND: The critical period during which the dietary supply of long-chain polyunsaturated fatty acids (LCPs) may influence the maturation of cortical function in term infants is unknown. OBJECTIVE: The aim of the present study was to determine the relative importance for maturation of the visual cortex of the dietary supply of LCPs during the first 6 wk of life compared with that during weeks 7-52. DESIGN: A randomized controlled clinical trial of LCP supplementation in 65 healthy term infants who were weaned from breast-feeding at 6 wk of age was conducted to determine whether the dietary supply of LCPs after weaning influenced the maturation of visual acuity and stereoacuity. RESULTS: Despite a dietary supply of LCPs from breast milk during the first 6 wk of life, infants who were weaned to formula that did not provide LCPs had significantly poorer visual acuity at 17, 26, and 52 wk of age and significantly poorer stereoacuity at 17 wk of age than did infants who were weaned to LCP-supplemented formula. Better acuity and stereoacuity at 17 wk was correlated with higher concentrations of docosahexaenoic acid in plasma. Better acuity at 52 wk was correlated with higher concentrations of docosahexaenoic acid in plasma and red blood cells. No significant effects of diet on growth were found. CONCLUSION: The results suggest that the critical period during which the dietary supply of LCPs can influence the maturation of cortical function extends beyond 6 wk of age

Self-perception in children aged 3 to 7 years with amblyopia and its association with deficits in vision and fine motor skills

Importance: Deficits in fine motor skills and slow reading speed have been reported in school-aged children and adults with amblyopia. These deficits were correlated with lower self-perception of athletic and cognitive competence. Although perceived competence and social acceptance are key determinants of developing self-perception in young children, the association of amblyopia with self-perception and the association of altered self-perception with fine motor skills to date have not been reported for young children aged 3 to 7 years. Objectives: To investigate whether amblyopia is associated with altered self-perception in young children and to assess whether any differences in self-perception are associated with deficits in vision and fine motor skills. Design, Setting, and Participants: In this cross-sectional study, conducted at a pediatric vision laboratory from January 10, 2016, to May 4, 2018, healthy children aged 3 to 7 years (preschool to second grade) were enrolled, including 60 children with amblyopia; 30 children who never had amblyopia but had been treated for strabismus, anisometropia, or both; and 20 control children. Main Outcomes and Measures: Self-perception was assessed using the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children, which includes the following 4 specific domains: cognitive competence, peer acceptance, physical competence, and maternal acceptance (total score range, 1-4; higher scores indicate higher perceived competence or acceptance). Fine motor skills were evaluated with the Manual Dexterity and Aiming and Catching scales of the Movement Assessment Battery for Children, second edition (score range, 1-19; higher scores indicate better skill performance). Visual acuity and stereoacuity also were assessed. Results: Children with amblyopia (28 girls and 32 boys; mean [SD] age, 6.3 [1.3] years) had significantly lower mean (SD) peer acceptance and physical competence scores compared with the control children (peer acceptance, 2.74 [0.66] vs 3.11 [0.36]; mean difference, 0.37; 95% CI for difference, 0.06-0.68; P =.04; and physical competence, 2.86 [0.60] vs 3.43 [0.52]; mean difference, 0.57; 95% CI for difference, 0.27-0.87; P =.009). Among the children with amblyopia, self-perception of physical competence was significantly correlated with aiming and catching skills (r = 0.43; 95% CI, 0.10-0.67; P =.001) and stereoacuity (r = -0.39; 95% CI, -0.05 to -0.65; P =.02). Children treated for strabismus or anisometropia, but who never had amblyopia, also had significantly lower mean (SD) physical competence scores compared with control children (2.89 [0.54] vs 3.43 [0.52]; 95% CI for difference, 0.23-0.85; P =.03). Conclusions and Relevance: These findings suggest that lower self-perception of peer acceptance and physical competence identify the broad effects of altered visual development in the everyday life of children with amblyopia..</p

Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized clinical trial.

OBJECTIVE: Breast-fed infants receive docosahexaenoic acid (DHA) and arachidonic acid (ARA) in their diet. Upon weaning, infants lose this dietary source of long-chain polyunsaturates because many commercial formulas do not contain these important constituents for neural membrane biogenesis. We evaluated the benefits of postweaning dietary supplementation of DHA + ARA on visual maturation. STUDY DESIGN: Healthy term infants (n = 61) were breast-fed to 4 to 6 months, then were randomly assigned to commercial formula or formula supplemented with DHA (0.36%) + ARA (0.72%). Measurements of red blood cell (RBC) fatty acids, visually evoked potential (VEP) acuity, and stereoacuity were done before and after weaning. RESULTS: At 1 year of age, RBC-DHA in the commercial formula-fed group was reduced by 50% from the weaning level, whereas there was a 24% increase in the DHA + ARA-supplemented group. The primary outcome measure, VEP acuity, was significantly more mature in supplemented infants at 1 year of age. Elevated RBC-DHA levels were associated with more mature VEP acuity. There were no significant diet-related differences in stereoacuity. CONCLUSIONS: These data extend through the first year of life the critical period in which a dietary supply of DHA and ARA can contribute in optimizing visual development in term infants

Quality of life and functional vision across pediatric eye conditions assessed using the PedEyeQ

Purpose: To evaluate eye-related quality of life (ER-QOL) and functional vision across a wide range of pediatric eye conditions, using the Pediatric Eye Questionnaires (PedEyeQ). Methods: A total of 1,037 children with an eye condition and 254 visually normal controls, across 0-4, 5-11, and 12-17 years age groups, completed the following questionnaires: Child PedEyeQ (Functional Vision, Bothered by Eyes/Vision, Social, Frustration/Worry domains), Proxy PedEyeQ (same domains plus Eye Care), and Parent PedEyeQ (Impact on Parent and Family, Worry about Child's Eye Condition, Worry about Child's Self-perception and Interactions, and Worry about Functional Vision domains). The primary eye condition was classified as amblyopia (n = 171), cataract (n = 99), cerebral visual impairment (CVI; n = 50), cornea (n = 20), eyelid (n = 35), glaucoma (n = 24), nystagmus (n = 57), orbital (n = 19), pupil/iris (n = 7), refractive error (n = 119), retina (n = 82), strabismus (n = 332), and uveitis (n = 22). Results: PedEyeQ domain scores (scaled 0-100) were significantly worse across eye conditions, compared with controls. Child PedEyeQ greatest differences were on the Bothered by Eyes/Vision domain (nystagmus 5-11 years, −26 points [95% CI, −39 to −12]; nystagmus 12-17 years, −45 [95% CI, −61 to −28]). Proxy PedEyeQ differences were greatest on Functional Vision (CVI 0-4 years, −45 [95% CI, −56 to −34]; CVI 5-11 years, −58 [95% CI, −72 to −43]; nystagmus 12-17 years, −50 [95% CI, −69 to −31]). Parent PedEyeQ differences were greatest on Worry about Child's Functional Vision (CVI 0-4 years, −64; 95% CI −77 to −50). Conclusions: The PedEyeQ detects reduced ER-QOL and functional vision across pediatric eye conditions, and across age groups, indicating its utility for clinical practice and clinical trials. © 2021 American Association for Pediatric Ophthalmology and Strabismus12 month embargo; first published online 16 February 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Association of Visual Acuity with Eye-Related Quality of Life and Functional Vision Across Childhood Eye Conditions

Purpose: We evaluated relationships between visual acuity (VA) and eye-related quality of life and functional vision in children, across a spectrum of pediatric eye conditions, using the Pediatric Eye Questionnaire (PedEyeQ). Design: Cross-sectional study. Methods: Three hundred ninety-seven children (5-11 years of age) with an eye condition and 104 visually normal control subjects completed the Child PedEyeQ (functional vision, bothered by eyes/vision, social, and frustration/worry domains). One parent for each child completed the Proxy PedEyeQ (same domains as child plus eye care) and parent PedEyeQ (impact on parent and family, worry about child's eye condition, worry about child's self-perception and interactions, and worry about functional vision domains). Each domain was Rasch-scored and Spearman rank correlations were calculated to evaluate relationships between better-seeing-eye and worse-seeing-eye VA and PedEyeQ domain score. Results: There was a significant relationship between poorer better-seeing-eye VA and lower (worse) PedEyeQ score on 2 of 4 child domains (e.g., functional vision, r = −0.1474; P = .005), on 2 of 5 proxy PedEyeQ domains (e.g., functional vision, r = −0.2183; P < .001), and on 2 of 4 parent PedEyeQ domains (e.g., impact on parent and family, r = −0.1607; P = .001). Worse-seeing-eye VA was associated with lower PedEyeQ scores across all child, proxy and parent domains (P < .01 for each) with the exception of the child social domain (P = .15). Conclusions: Both better-seeing-eye and worse-seeing-eye VA were associated with functional vision and eye-related quality of life in children, assessed using the PedEyeQ, although other factors may also influence relationships. These data further validate using the PedEyeQ across pediatric eye conditions. © 2020 Elsevier Inc.National Institutes of Health12 month embargo; available online 28 October 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]