A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function.

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function

Results of SemTab 2022

SemTab 2022 was the fourth edition of the Semantic Web Challenge on Tabular Data to Knowledge Graph Matching, successfully collocated with the 21st International Semantic Web Conference (ISWC) and the 17th Ontology Matching (OM) Workshop. SemTab provides a common framework to conduct a systematic evaluation of state-of-the-art systems. In this paper, we give an overview of the 2022’s edition of the challenge and summarize the results

The recurrent missense mutation p.(Arg367Trp) in YARS1 causes a distinct neurodevelopmental phenotype

Abstract: Pathogenic variants in aminoacyl-tRNA synthetases (ARS1) cause a diverse spectrum of autosomal recessive disorders. Tyrosyl tRNA synthetase (TyrRS) is encoded by YARS1 (cytosolic, OMIM*603,623) and is responsible of coupling tyrosine to its specific tRNA. Next to the enzymatic domain, TyrRS has two additional functional domains (N-Terminal TyrRSMini and C-terminal EMAP-II-like domain) which confer cytokine-like functions. Mutations in YARS1 have been associated with autosomal-dominant Charcot-Marie-Tooth (CMT) neuropathy type C and a heterogenous group of autosomal recessive, multisystem diseases. We identified 12 individuals from 6 families with the recurrent homozygous missense variant c.1099C > T;p.(Arg367Trp) (NM_003680.3) in YARS1. This variant causes a multisystem disorder with developmental delay, microcephaly, failure to thrive, short stature, muscular hypotonia, ataxia, brain anomalies, microcytic anemia, hepatomegaly, and hypothyroidism. In silico analyses show that the p.(Arg367Trp) does not affect the catalytic domain responsible of enzymatic coupling, but destabilizes the cytokine-like C-terminal domain. The phenotype associated with p.(Arg367Trp) is distinct from the other biallelic pathogenic variants that reside in different functional domains of TyrRS which all show some common, but also divergent clinical signs [(e.g., p.(Phe269Ser)—retinal anomalies, p.(Pro213Leu)/p.(Gly525Arg)—mild ID, p.(Pro167Thr)—high fatality)]. The diverse clinical spectrum of ARS1-associated disorders is related to mutations affecting the various non-canonical domains of ARS1, and impaired protein translation is likely not the exclusive disease-causing mechanism of YARS1- and ARS1-associated neurodevelopmental disorders. Key messages: The missense variant p.(Arg367Trp) in YARS1 causes a distinct multisystem disorder.p.(Arg367Trp) affects a non-canonical domain with cytokine-like functions.Phenotypic heterogeneity associates with the different affected YARS1 domains.Impaired protein translation is likely not the exclusive mechanism of ARS1-associated disorders

Understanding consumer demand for new transport technologies and services, and implications for the future of mobility

The transport sector is witnessing unprecedented levels of disruption. Privately owned cars that operate on internal combustion engines have been the dominant modes of passenger transport for much of the last century. However, recent advances in transport technologies and services, such as the development of autonomous vehicles, the emergence of shared mobility services, and the commercialization of alternative fuel vehicle technologies, promise to revolutionise how humans travel. The implications are profound: some have predicted the end of private car dependent Western societies, others have portended greater suburbanization than has ever been observed before. If transport systems are to fulfil current and future needs of different subpopulations, and satisfy short and long-term societal objectives, it is imperative that we comprehend the many factors that shape individual behaviour. This chapter introduces the technologies and services most likely to disrupt prevailing practices in the transport sector. We review past studies that have examined current and future demand for these new technologies and services, and their likely short and long-term impacts on extant mobility patterns. We conclude with a summary of what these new technologies and services might mean for the future of mobility.Comment: 15 pages, 0 figures, book chapte

NetKet: A machine learning toolkit for many-body quantum systems

We introduce NetKet, a comprehensive open source framework for the study of many-body quantum systems using machine learning techniques. The framework is built around a general and flexible implementation of neural-network quantum states, which are used as a variational ansatz for quantum wavefunctions. NetKet provides algorithms for several key tasks in quantum many-body physics and quantum technology, namely quantum state tomography, supervised learning from wavefunction data, and ground state searches for a wide range of customizable lattice models. Our aim is to provide a common platform for open research and to stimulate the collaborative development of computational methods at the interface of machine learning and many-body physics

Results of SemTab 2023

SemTab 2023 was the fifth edition of the Semantic Web Challenge on Tabular Data to Knowledge Graph Matching, collocated with the 22nd International Semantic Web Conference (ISWC) and the 18th Ontology Matching (OM) Workshop. SemTab provides a framework to conduct a systematic evaluation of state-of-the-art semantic table interpretation systems. In this paper, we give an overview of the 2023 edition of the challenge and summarize the results

Pure cerebellar ataxia due to bi-allelic PRDX3 variants including recurring p.Asp202Asn

Bi-allelic variants in peroxiredoxin 3 (PRDX3) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported PRDX3 variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent-onset pure and complex cerebellar ataxia