Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Background As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Results We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.[Background] As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited.[Objective] The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.[Methods] We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.[Results] We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.[Conclusions] Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.This project was funded by The Michael J. Fox Foundation (ID 15015.02)Peer reviewe

Revista del Museo Nacional N° 46

El Museo Nacional, dirigido por Luis E. Valcárcel desde 1931, publicó la Revista del Museo Nacional a partir del año 1932. El presente volumen N° XLVI, fue publicado en 1982. Contenido: “A Luis E. Valcárcel”, por José Antonio del Busto Duthurburu – “Una contribución al conocimiento del Perú” – “El complejo Chivateros: una aproximación tecnológica”, por Duccio Bonavia – “Patrones prehispánicos de uso de diversos tipos de piedra en la región del río Cunas, Huancayo”, por Luis Hurtado de Mendoza – “ Telarmachay: niveles precerámicos de ocupación, por Daniéle Lavallée, Michéle Julien, Jane Wheeler : Apéndice. Análisis funcional preliminar de instrumentos líticos tallados de Telarmachay, por P. Vaughan – “Materiales arqueológicos de Garagay”, por Rogger Ravines, Helen Engelstad, Victoria Palomino, Daniel H. Sandweiss – “La caza del venado en el arte mochica”, por Christopher B. Donnan – “Modelos arquitectónicos peruanos. Ensayo de interpretación”, por Wolfgang W. Wurster – “Vivir con crisis: percepción humana de proceso y tiempo”, por Michael E. Moseley, Robert Feldman -- Apéndice. Metodología del sistema de Galindo para predecir la magnitud de las inundaciones, por Charles R. Ortloff – “El reino de Cuismanco”, por Fernando Silva Santisteban – “Las ‘provincias’ inca del antiguo Tucumán”, por Alberto Rex González – “Contribución al estudio de las antiguas técnicas de deformación cefálica en la costa del Perú”, por Paulette Reichlen

T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children

Background: The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, .90% of the population was DENV-naı¨ve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection. Methods: We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers. Lymphocyte T helper (Th) 1, Th2, Th17 and inflammatory responses were assayed in blood during the 2009 DENV-1 epidemic. Results: The immune response to DENV-1 was significantly biased to Th2 in infected infants and young children, compared to infants with other febrile illnesses (for IL-4 p,0.001) and to their infected mothers (for IL-4 p,0.01). In addition, IL-17 suppression was observed in the memory response to DENV-1 in infected infants (p,0.01 vs placebo). Conclusion: Age-related differences in the primary response to DENV, characterized by an immature Th2 polarization and Th17 suppression in infants, should be studied further in order to expand our understanding of the mechanism of dengue pathogenesis.Fil: Talarico, Laura Beatriz. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bugna Hortoneda, Jimena. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Wimmenauer, Vera. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Espinoza, Marco A.. Hospital San Vicente de Paul; ArgentinaFil: Quipildor, Marcelo O.. Hospital San Vicente de Paul; ArgentinaFil: Hijano, Diego R.. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Beccaria, Martín. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Wurster, Victoria. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Cavagnaro, Luis E.. Hospital SAMIC Iguazu; ArgentinaFil: Martinez, Daniel. Hospital SAMIC Iguazu; ArgentinaFil: Fattore, Gladys. Fundación Mundo Sano; ArgentinaFil: Batalle, Juan Pio. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reynoso, Natalia. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Melendi, Guillermina Amanda. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; ArgentinaFil: Rey, Felix A.. Institut Pasteur. Département de Virologie. Unité de Virologie Structurale; FranciaFil: Libster, Romina Paula. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polack, Fernando Pedro. Vanderbilt University. Department of Pediatrics; Estados Unidos. Fundación para la Investigación en Infectologia Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Embracing monogenic parkinson's disease:the MJFF global genetic PD cohort

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials