Common Variants in the Gene with Unclear Pathogenicity as the Cause of Oculocutaneous Albinism in a Cohort of Russian Patients.

oculocutaneous albinism (OCA) is a hereditary impairment of skin, hair, and eye pigmentation. The most common form of albinism is autosomal recessive albinism, caused by mutations in the gene, accounting for approximately 40-50% of all cases of the disease in European populations. Common hypomorphic variants in the gene could lead to a mild form of albinism in a compound heterozygous state with a pathogenic variant.

[Developmental and epileptic encephalopathy produced by the ATP1A2 mutation].

A case of DEE98, a rare developmental and epileptic encephalopathy related to previously reported the missense mutation p.Arg908Gln in the gene, is described. A girl examined first time in 11 months had microcephaly, severe mental and motor delay, strabismus, spastic paraparesis and pachypolymicrogyria on brain MRI that is atypical for DEE98.

Nutritional strategies modulating the gut microbiome as a preventative and therapeutic approach in normal and pathological age-related cognitive decline: a systematic review of preclinical and clinical findings.

Context: The proportion of the elderly population is on the rise across the globe, and with it the prevalence of age-related neurodegenerative diseases. The gut microbiota, whose composition is highly regulated by dietary intake, has emerged as an exciting research field in neurology due to its pivotal role in modulating brain functions via the gut-brain axis.

Objectives: We aimed at conducting a systematic review of preclinical and clinical studies investigating the effects of dietary interventions on cognitive ageing in conjunction with changes in gut microbiota composition and functionality.

Clinical Characterization of Alagille Syndrome in Patients with Cholestatic Liver Disease.

Alagille syndrome (ALGS) is a multisystem condition characterized by cholestasis and bile duct paucity on liver biopsy and variable involvement of the heart, skeleton, eyes, kidneys, and face and caused by pathogenic variants in the or gene. The variable expressivity of the clinical phenotype and the lack of genotype-phenotype correlations lead to significant diagnostic difficulties. Here we present an analysis of 18 patients with cholestasis who were diagnosed with ALGS.

Mesoscale Simulations of Structure Formation in Polyacrylonitrile Nascent Fibers Induced by Binary Solvent Mixture.

Polyacrylonitrile (PAN) is widely used as a raw material for the production of high-modulus carbon fibers, the internal structure of which is directly affected by the spinning of the precursor. Although PAN fibers have been studied for a long time, the formation of their internal structure has not been sufficiently investigated theoretically. This is due to the large number of stages in the process and the parameters controlling them.

Serotonin reuptake transporter deficiency promotes liver steatosis and impairs intestinal barrier function in obese mice fed a Western-style diet.

Background: Intestinal barrier dysfunctions have been associated with liver steatosis and metabolic diseases. Besides nutritional factors, like a Western-style diet (WSD), serotonin has been linked with leaky gut. Therefore, we aimed to evaluate the role of serotonin in the pathogenesis of intestinal barrier dysfunctions and liver steatosis in mice fed high-fat and high-sugar diets.

Spectrum of Genes for Non--Related Non-Syndromic Hearing Loss in the Russian Population Revealed by a Targeted Deafness Gene Panel.

Hearing loss is one of the most genetically heterogeneous disorders known. Over 120 genes are reportedly associated with non-syndromic hearing loss (NSHL). To date, in Russia, there have been relatively few studies that apply massive parallel sequencing (MPS) methods to elucidate the genetic factors underlying non-GJB2-related hearing loss cases.

Identification of a Novel de Novo Variant in the CASZ1 Causing a Rare Type of Dilated Cardiomyopathy.

Unlabelled: A new de novo frameshift variant has been identified in the CASZ1 gene leading to severe dilated cardiomyopathy.

Methods: The proband was analyzed with WES NGS, post-mortem, using dried blood spots on filters. The variant was verified with Sanger sequencing for the proband and her parents.

Serotonin Receptor 5-HT Regulates TrkB Receptor Function in Heteroreceptor Complexes.

Serotonin receptor 5-HT and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT receptor expression.

Congenital myopathy as a new phenotype caused by two undescribed variants in ASCC1 gene.

We present a patient with congenital myopathy and an inborn epiphysiolysis of the ulna. Whole-exome sequencing analysis revealed two novel mutations in Activation Signal Cointegrator Complex 1 (ASCC1) gene in a compound heterozygous state-a splicing variant c.395-2A>G and a deletion of the first two coding exons.

Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene.

Background: Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific features such as disproportionate nanism, generalized osteosclerosis, and distinct craniofacial dysmorphism. Radiographic features include acro-osteolysis of the distal phalanges in association with sclerosing bone lesions with multiple fractures. The polymorphism of the clinical manifestations of pycnodysostosis and low prevalence of the disorder lead to the difficulties with early.

mRNA analysis revealed a novel pathogenic EIF2S3 variant causing MEHMO syndrome.

EIF2S3 pathogenic variants have been shown to cause MEHMO syndrome - a rare X-linked intellectual disability syndrome. In most cases, DNA diagnostics of MEHMO syndrome is performed using exome sequencing. We describe two cousins with profound intellectual disability, severe microcephaly, microgenitalism, hypoglycemia, epileptic seizures, and hypertrichosis, whose clinical symptoms allowed us to suspect MEHMO syndrome.

Effect of Nanoparticles Surface Bonding and Aspect Ratio on Mechanical Properties of Highly Cross-Linked Epoxy Nanocomposites: Mesoscopic Simulations.

The paper aims to study the mechanical properties of epoxy resin filled with clay nanoparticles (NPs), depending on their shapes and content on the surface of a modifying agent capable of forming covalent bonds with a polymer. The cylindrical clay nanoparticles with equal volume and different aspects ratios (disks, barrel, and stick) are addressed. The NPs' bonding ratio with the polymer () is determined by the fraction of reactive groups and conversion time and varies from = 0 (non-bonded nanoparticles) to = 0.

Regulation of the gut barrier by carbohydrates from diet - Underlying mechanisms and possible clinical implications.

The gut barrier has been recognized as being of relevance in the pathogenesis of multiple different diseases ranging from inflammatory bowel disease, irritable bowel syndrome, inflammatory joint disease, fatty liver disease, and cardiometabolic disorders. The regulation of the gut barrier is, however, poorly understood. Especially, the role of food components such as sugars and complex carbohydrates has been discussed controversially in this respect.

[AP4-assocated hereditary spastic paraplegias].

Objective: In the course of studies of spastic paraplegias in Russian patients to detect AP4-associated forms, estimate their proportion in the total SPG group and analyze clinical and molecular characteristics.

Material And Methods: Five families of Russian ethnicity: four with SPG47, one with SPG51 (4 girls and a boy aged 2.5-9 years) were studied.

Alkaptonuria in Russia: mutational spectrum and novel variants.

Alkaptonuria is a rare genetic disease caused by mutations in HGD gene. Here we report the results of genetic and biochemical analysis of 49 Russian patients with alkaptonuria. One of the common variants c.

Development of Human iPSC-Derived Functional Neuronal Networks on Laser-Fabricated 3D Scaffolds.

Neural progenitor cells generated from human induced pluripotent stem cells (hiPSCs) are the forefront of ″brain-on-chip″ investigations. Viable and functional hiPSC-derived neuronal networks are shaping powerful models for evaluating the normal and abnormal formation of cortical circuits, understanding the underlying disease mechanisms, and investigating the response to drugs. They therefore represent a desirable instrument for both the scientific community and the pharmacological industry.

The 5-HT receptor interacts with adhesion molecule L1 to modulate morphogenic signaling in neurons.

Morphological remodeling of dendritic spines is critically involved in memory formation and depends on adhesion molecules. Serotonin receptors are also implicated in this remodeling, though the underlying mechanisms remain enigmatic. Here, we uncovered a signaling pathway involving the adhesion molecule L1CAM (L1) and serotonin receptor 5-HT (5-HTR, encoded by ).

Additive-induced ordered structures formed by PCBM fullerene derivatives.

We report the results of an experimental and theoretical study of structure formation in mixtures of phenyl-C-butyric acid methyl ester (PCBM) with high boiling octane based solvent additives 1,8-octanedithiol (ODT), 1,8-dibromooctane, and 1,8-diiodooctane obtained by evaporation of a host-solvent (chlorobenzene). Experimental studies by DSC, SAXS and WAXS methods found evidence of crystallization of fullerenes in the presence of the high boiling additives in the mixtures. A molecular dynamics simulation of a PCBM/ODT mixture revealed the self-assembly of fullerenes into sponge-like network structures.

Identification of novel variants in the gene in Russian patients with familial hypercholesterolemia using targeted sequencing.

Familial hypercholesterolemia (FH) is caused by mutations in various genes, including the , and genes; however, the spectrum of these mutations in Russian individuals has not been fully investigated. In the present study, mutation screening was performed on the gene and other FH-associated genes in patients with definite or possible FH, using next-generation sequencing. In total, 59 unrelated patients were recruited and sorted into two separate groups depending on their age: Adult (n=31; median age, 49; age range, 23-70) and children/adolescent (n=28; median age, 11; age range, 2-21).

Prokinetic actions of luminally acting 5-HT receptor agonists.

Background: 5-HT receptor (5-HT R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT Rs have limited their use. Since 5-HT Rs are expressed in the colonic epithelium and their stimulation accelerates colonic propulsion in vitro, we tested whether luminally acting 5-HT R agonists promote intestinal motility.

Methods: Non-absorbed 5-HT R agonists, based on prucalopride and naronapride, were assessed for potency at the 5-HT R in vitro, and for tissue and serum distribution in vivo in mice.

Amelioration of Tau pathology and memory deficits by targeting 5-HT7 receptor.

Tauopathies comprise a heterogeneous family of neurodegenerative diseases characterized by pathological accumulation of hyperphosphorylated Tau protein. Pathological changes in serotonergic signaling have been associated with tauopathy etiology, but the underlying mechanisms remain poorly understood. Here, we studied the role of the serotonin receptor 7 (5-HT7R), in a mouse model of tauopathy induced by overexpressing the human Tau[R406W] mutant associated with inherited forms of frontotemporal dementia.

KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families.

Background: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population.

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels.

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown.