The expression level of VEGFR2 regulates mechanotransduction, tumor growth and metastasis of high grade serous ovarian cancer cells.

Recent data shows that alterations in the expression and/or activation of the vascular endothelial growth factor receptor 2 (VEGFR2) in high grade serous ovarian cancer (HGSOC) modulate tumor progression. However, controversial results have been obtained, showing that in some cases VEGFR2 inhibition can promote tumorigenesis and metastasis. Thus, it is urgent to better define the role of the VEGF/VEGFR2 system to understand/predict the effects of its inhibitors administered as anti-angiogenic in HGSOC.

Choice of compound, dosage, and management of side effects for long-term corticosteroid treatment in Duchenne muscular dystrophy: Guidelines from the Neuromuscular Commission of the French Society of Pediatric Neurology.

The French Society of Pediatric Neurology and the FILNEMUS network created a working group on corticosteroid therapy in children with Duchenne muscular dystrophy in order to analyze the literature review and current French practices. The aim of this work was to produce guidelines regarding treatment initiation, pre-therapeutic interventions, choice between available compounds, and treatment monitoring (dosage, duration, and discontinuation). The treatment side effects and their management are also detailed: osteoporosis, endocrinological anomaly (growth delay, weight gain, pubertal delay), cataract, arterial hypertension, behavioral disorders, management of immunosuppression and vaccines, and management of gastrointestinal and metabolic complications.

Mutation in the Kinase Domain Alters the VEGFR2 Membrane Dynamics.

Background: Recently, the substitution R1051Q in VEGFR2 has been described as a cancer-associated "gain of function" mutation. VEGFR2 phosphorylation is ligand-independent and enhances the activation of intracellular pathways and cell growth both in vitro and in vivo. In cancer, this mutation is found in heterozygosity, suggesting that an interaction between VEGFR2 and VEGFR2 may occur and could explain, at least in part, how VEGFR2 acts to promote VEGFR2 signaling.

Correction: Alternative method to visualize receptor dynamics in cell membranes.

[This corrects the article DOI: 10.1371/journal.pone.

CHD8-related disorders redefined: an expanding spectrum of dystonic phenotypes.

Background: Heterozygous loss-of-function variants in CHD8 have been associated with a syndromic neurodevelopmental-disease spectrum, collectively referred to as CHD8-related neurodevelopmental disorders. Several different clinical manifestations, affecting neurodevelopmental and systemic domains, have been described, presenting with highly variable expressivity. Some expressions are well established and comprise autism spectrum disorders, psychomotor delay with cognitive impairment, postnatal overgrowth with macrocephaly, structural brain abnormalities, gastrointestinal disturbances, and behavioral and sleep-pattern problems.

The D647N mutation of FGFR1 induces ligand-independent receptor activation.

The activation loop (A-loop) of kinases, a key regulatory region, is recurrently mutated in several kinase proteins in cancer resulting in dysregulated kinase activity and response to kinase inhibitors. FGFR1 receptor tyrosine kinase represents an important oncogene and therapeutic target for solid and hematological tumors. Here we investigate the biochemical and molecular effects of D647N mutation lying in the A-loop of FGFR1.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants.

Loss-of-function variants in cause a syndromic neurodevelopmental disorder.

Purpose: variants in (Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants in describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.

Methods: Genetic data and detailed clinical records were collected via multi-center collaboration.

Deficiency of AP1 Complex in Zebrafish Model Led to Perturbation of Neurodevelopment, Female and Male Fertility; New Insight to Understand Adaptinopathies.

In vertebrates, two homologous heterotetrameric AP1 complexes regulate the intracellular protein sorting via vesicles. AP-1 complexes are ubiquitously expressed and are composed of four different subunits: γ, β1, μ1 and σ1. Two different complexes are present in eukaryotic cells, AP1G1 (contains γ1 subunit) and AP1G2 (contains γ2 subunit); both are indispensable for development.

Mechanobiology of the relocation of proteins in advecting cells: in vitro experiments, multi-physics modeling, and simulations.

Cell motility-a cellular behavior of paramount relevance in embryonic development, immunological response, metastasis, or angiogenesis-demands a mechanical deformation of the cell membrane and influences the surface motion of molecules and their biochemical interactions. In this work, we develop a fully coupled multi-physics model able to capture and predict the protein flow on endothelial advecting plasma membranes. The model has been validated against co-designed in vitro experiments.

Highlighting the Dystonic Phenotype Related to GNAO1.

Background: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea.

Objective: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders.

Methods: We included patients diagnosed with GNAO1-related movement disorders of delayed onset (>2 years).

Production and Biochemical Characterization of Dimeric Recombinant Gremlin-1.

Gremlin-1 is a secreted cystine-knot protein that acts as an antagonist of bone morphogenetic proteins (BMPs), and as a ligand of heparin and the vascular endothelial growth factor receptor 2 (VEGFR2), thus regulating several physiological and pathological processes, including embryonic development, tissue fibrosis and cancer. Gremlin-1 exerts all these biological activities only in its homodimeric form. Here, we propose a multi-step approach for the expression and purification of homodimeric, fully active, histidine-tagged recombinant gremlin-1, using mammalian HEK293T cells.

Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes.

Background: Adipose tissue plays a pivotal role in the development and progression of the metabolic syndrome which along with its complications is an epidemic of the 21st century. Irisin is an adipo-myokine secreted mainly by skeletal muscle and targeting, among others, adipose tissue. In brown adipose tissue it upregulates uncoupling protein-1 (UCP1) which is responsible for mitochondrial non-shivering thermogenesis.

Glyco-Coated CdSe/ZnS Quantum Dots as Nanoprobes for Carbonic Anhydrase IX Imaging in Cancer Cells.

The bioimaging of cancer cells by the specific targeting of overexpressed biomarkers is an approach that holds great promise in the identification of selective diagnostic tools. Tumor-associated human carbonic anhydrase (hCA) isoforms IX and XII have been considered so far as well-defined biomarkers, with their expression correlating with cancer progression and aggressiveness. Therefore, the availability of highly performant fluorescent tools tailored for their targeting and able to efficiently visualize such key targets is in high demand.

Novel potential oncogenic and druggable mutations of FGFRs recur in the kinase domain across cancer types.

Fibroblast growth factor receptors (FGFRs) are recurrently altered by single nucleotide variants (SNVs) in many human cancers. The prevalence of SNVs in FGFRs depends on the cancer type. In some tumors, such as the urothelial carcinoma, mutations of FGFRs occur at very high frequency (up to 60%).

Protein domain-based approaches for the identification and prioritization of therapeutically actionable cancer variants.

The tremendous number of cancer variants that can be detected by NGS analyses has required the development of computational approaches to prioritize mutations on the basis of their biological and clinical significance. Standard strategies take a gene-centric approach to the problem, allowing exclusively the identification of highly frequent variants. On the contrary, protein domain (PD)-based approaches allow to identify functionally relevant low frequency variants by searching for mutations that recur on analogous residues across homologous proteins (i.

Tremor-like subcortical myoclonus in STXBP1 encephalopathy.

The phenotypic spectrum of STXBP1-related encephalopathy ranges from infantile epileptic encephalopathy to intellectual disability with nonsyndromic or absent epilepsy. Although being frequently reported, the tremor associated with STXBP1 has not been fully characterized to date. The aim of our study was to describe it.