Recent Submissions

The Transcription Factor FEZF1, a Direct Target of EWSR1-FLI1 in Ewing Sarcoma Cells, Regulates the Expression of Neural-Specific Genes. 

Ewing sarcoma is a rare pediatric tumor characterized by chromosomal translocations that give rise to aberrant chimeric transcription factors (e.g., EWSR1-FLI1). EWSR1-FLI1 promotes a specific cellular transcriptional program. Therefore, the study of EWSR1-FLI1 target genes is important to identify...

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. 

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all ava...

Vigilancia de las enfermedades raras en España: el Registro Estatal de Enfermedades Raras 

[ES] Tradicionalmente la vigilancia epidemiológica se ha centrado en enfermedades transmisibles, pero el concepto de vigilancia en Salud Pública, incorporado en España con la Ley 33/2011, es más amplio e incluye las enfermedades crónicas. Las estrategias de salud para estas enfermedad...

Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer. 

Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably 'silent' genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) o...

Intervention Services for Autistic Adults: An ASDEU Study of Autistic Adults, Carers, and Professionals' Experiences. 

The Autism Spectrum Disorders in the European Union (ASDEU) survey investigated local services' use experiences of autistic adults, carers and professionals with interventions for autistic adults. The majority of the 697 participants experienced recommended considerations prior to deciding on inter...

CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration. 

Regeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler CHD4, a member of the nucleosome remodeling and deacetylase (NuRD) repressive complex, is essential for the expansion and regenerative functions of satellite cells. We s...

Therapeutic Potential of EWSR1-FLI1 Inactivation by CRISPR/Cas9 in Ewing Sarcoma. 

Ewing sarcoma is an aggressive bone cancer affecting children and young adults. The main molecular hallmark of Ewing sarcoma are chromosomal translocations that produce chimeric oncogenic transcription factors, the most frequent of which is the aberrant transcription factor EWSR1-FLI1. Because this...

Deep Phenotyping and Genetic Characterization of a Cohort of 70 Individuals With 5p Minus Syndrome. 

Chromosome-5p minus syndrome (5p-Sd, OMIM #123450) formerly known as Cri du Chat syndrome results from the loss of genetic material at the distal region of the short arm of chromosome 5. It is a neurodevelopmental disorder of genetic cause. So far, about 400 patients have been reported worldwide. I...

Prevention of Neural Tube Defects in Europe: A Public Health Failure. 

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first ...

Hippo pathway effectors YAP1/TAZ induce an EWS-FLI1-opposing gene signature and associate with disease progression in Ewing sarcoma. 

YAP1 and TAZ (WWTR1) oncoproteins are the final transducers of the Hippo tumor suppressor pathway. Deregulation of the pathway leads to YAP1/TAZ activation fostering tumorigenesis in multiple malignant tumor types, including sarcoma. However, oncogenic mutations within the core components of the Hi...

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders. 

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we ...

EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway. 

Ewing sarcoma (ES) is an aggressive pediatric tumor driven by the fusion protein EWS-FLI1. We report that EWS-FLI1 suppresses TDO2-mediated tryptophan (TRP) breakdown in ES cells. Gene expression and metabolite analyses reveal an EWS-FLI1-dependent regulation of TRP metabolism. TRP consumption incr...

Development of Macrocycle Kinase Inhibitors for ALK2 Using Fibrodysplasia Ossificans Progressiva-Derived Endothelial Cells. 

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare congenital form of heterotopic ossification (HO), caused by heterozygous mutations in the activin A type I receptor (ACVR1), that encodes the bone morphogenetic protein (BMP) type I receptor ALK2. These mutations enable ALK2 to induce...

Autistic Adult Health and Professional Perceptions of It: Evidence From the ASDEU Project 

The Autism Spectrum Disorders in the European Union (ASDEU) survey investigated the knowledge and health service experiences of users and providers to generate new hypotheses and scientific investigations that would contribute to improvement in health care for autistic adults. An online survey desi...

Polymerization of misfolded Z alpha-1antitrypin protein lowers CX3CR1 expression in human PBMCs. 

The CX3CR1 (chemokine (C-X3-C motif) receptor 1) expression levels on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expressio...

Screening for autism spectrum disorders: state of the art in Europe. 

A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies' findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to ce...

Role of Chromodomain-Helicase-DNA-Binding Protein 4 (CHD4) in Breast Cancer. 

Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4-the core component of the nucleosome remodeling and deacetylase (NuRD) complex-may be mutated in...

RGB-Marking to Identify Patterns of Selection and Neutral Evolution in Human Osteosarcoma Models. 

Osteosarcoma (OS) is a highly aggressive tumor characterized by malignant cells producing pathologic bone; the disease presents a natural tendency to metastasize. Genetic studies indicate that the OS genome is extremely complex, presenting signs of macro-evolution, and linear and branched patterns ...

La Red de investigación 'infancia y medio ambiente (Red INMA)": protocolo de estudio. 

[ES] Cada vez existe mayor evidencia de la influencia de la dieta y dela exposición a dosis bajas de tóxicos durante la etapa prenatal y primera infancia sobre la salud y el bienestar en etapas posteriores de lavida. Siguiendo las recomendaciones de la OMS y de la Unión Europea en el año 2003 se co...

Enfermedades raras: enfermedades crónicas que requieren un nuevo enfoque sociosanitario 

[ES] El concepto de Enfermedades Raras es relativamente nuevo. Suponen aquellos procesos que pueden ser mortales o provocar un debilitamiento crónico del paciente y que, debido a su escasa prevalencia, requieren esfuerzos combinados para tratarlas. A título indicativo, se considera una prevalencia ...