Search results for "Phenotype"

HNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans

2019

The heterogeneous nuclear ribonucleoprotein (HNRNP) genes code for a set of RNA-binding proteins that function primarily in the spliceosome C complex. Pathogenic variants in these genes can drive neurodegeneration, through a mechanism involving excessive stress-granule formation, or developmental defects, through mechanisms that are not known. Here, we report four unrelated individuals who have truncating or missense variants in the same C-terminal region of hnRNPR and who have multisystem developmental defects including abnormalities of the brain and skeleton, dysmorphic facies, brachydactyly, seizures, and hypoplastic external genitalia. We further identified in the literature a fifth ind…

Hematopoietic stem cell quiescence and function are controlled by the CYLD–TRAF2–p38MAPK pathway

2015

Tesio at al. identify a novel pathway controlled by the tumor suppressor and deubiquitinase cylindromatosis (CYLD), which is involved in the regulation of hematopoietic stem cell quiescence and repopulation potential.

Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy.

2014

Objective: To clarify the phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathies. Methods: We screened for TRPV4 mutations in 169 French unrelated patients with inherited axonal peripheral neuropathy. Ninety-five patients had dominant Charcot-Marie-Tooth type 2 (CMT2) disease, and 74 patients, including 39 patients with distal hereditary motor neuropathy, 14 with congenital spinal muscular atrophy and arthrogryposis, 13 with CMT2, and 8 with scapuloperoneal spinal muscular atrophy, presented with additional vocal cord paralysis and/or skeletal dysplasia. Results: No deleterious TRPV4 mutation was identified in the 95 patients with “pure” CMT2 (0/…

Supervised Analysis for Phenotype Identification: The Case of Heart Failure Ejection Fraction Class

2021

Artificial Intelligence is creating a paradigm shift in health care, with phenotyping patients through clustering techniques being one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data from Electronic Health Records (EHR). Subjects and methods: 2854 subjects over 25 years old with a diagnosis of HF and LVEF, measured by echocardiography, were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. The performance of the developed algorithm was tested in heart failure patients from Primary Care. To select the mo…

The parasite's long arm: a tapeworm parasite induces behavioural changes in uninfected group members of its social host.

2015

Parasites can induce alterations in host phenotypes in order to enhance their own survival and transmission. Parasites of social insects might not only benefit from altering their individual hosts, but also from inducing changes in uninfected group members. Temnothorax nylanderi ant workers infected with the tapeworm Anomotaenia brevis are known to be chemically distinct from nest-mates and do not contribute to colony fitness, but are tolerated in their colonies and well cared for. Here, we investigated how tapeworm- infected workers affect colony aggression by manipulating their presence in ant colonies and analysing whether their absence or presence resulted in behavioural alterations in…

Design of Representations and Search Operators

2015

Successful and efficient use of evolutionary algorithms depends on the choice of genotypes and the representation – that is, the mapping from genotype to phenotype – and on the choice of search operators that are applied to the genotypes. These choices cannot be made independently of each other. This chapter gives recommendations on the design of representations and corresponding search operators and discusses how to consider problem-specific knowledge. For most problems in the real world, similar solutions have similar fitness values. This fact can be exploited by evolutionary algorithms if they ensure that the representations and search operators used are defined in such a way that simila…

Representations for evolutionary algorithms

2015

Successful and efficient use of evolutionary algorithms (EA) depends on the choice of the genotype, the problem representation (mapping from genotype to phenotype) and on the choice of search operators that are applied to the genotypes. These choices cannot be made independently of each other. The question whether a certain representation leads to better performing EAs than an alternative representation can only be answered when the operators applied are taken into consideration. The reverse is also true: deciding between alternative operators is only meaningful for a given representation. In EA practice one can distinguish two complementary approaches. The first approach uses indirect repr…

A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population.

2002

Myoadenylate deaminase deficiency is the most common metabolic disorder of skeletal muscle in the Caucasian population, affecting approximately 2% of all individuals. Although most deficient subjects are asymptomatic, some suffer from exercise-induced myalgia suggesting a causal relationship between a lack of enzyme activity and muscle function. In addition, carriers of this derangement in purine nucleotide catabolism may have an adaptive advantage related to clinical outcome in heart disease. The molecular basis of myoadenylate deaminase deficiency in Caucasians has been attributed to a single mutant allele characterized by double C to T transitions at nucleotides +34 and +143 in mRNA enco…

Paroxysmal nocturnal hemoglobinuria-like phenotype and thrombotic risk in several clinical disorders.

2021

Cytotoxicity and bioactivity of various pulpotomy materials on stem cells from human exfoliated primary teeth.

2017

Aims To investigate the cytotoxicity and bioactivity of several pulpotomy materials: Biodentine (Septodont, Saint-Maur-des-Fosses, France) MTA (Angelus, Londrina, PR, Brazil), Theracal LC (Bisco Inc., Schamburg, IL, USA) and IRM (Dentsply DeTrey GmbH, Konstanz, Germany), after contact with stem cells isolated from human exfoliated primary teeth (SHEDs). Methodology SHEDs were cultured in the presence of the eluates of various pulpotomy materials for 24, 48 and 72 h. Cell viability was determined by mitochondrial dehydrogenase enzymatic (MTT) assay. Apoptosis and changes in cell phenotype were evaluated by flow cytometry. Also, an in vitro scratch wound-healing assay was used to determine th…