EBS in Children with De Novo Pathogenic Variants Disturbing .

Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the gene, and indirect effects via pathogenic mutation in the gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14.

Bridging Gaps in HDR Improvement: The Role of MAD2L2, SCAI, and SCR7.

This study aimed to enhance homology-directed repair (HDR) efficiency in CRISPR/Cas-mediated genome editing by targeting three key factors regulating the balance between HDR and non-homologous end joining (NHEJ): MAD2L2, SCAI, and Ligase IV. In order to achieve this, a cellular model using mutated eGFP was designed to monitor HDR events. Results showed that MAD2L2 knockdown and SCR7 treatment significantly improved HDR efficiency during Cas9-mediated HDR repair of the mutated eGFP gene in the HEK293T cell line.

[Genome Editing in Therapy of Genodermatoses].

This review is devoted to the prospects for the use of fundamentally important approaches and methods for the correction and therapy of genodermatoses, a group of inherited skin diseases. The greatest number of methods was applicable for the group of inherited epidermolysis bullosa. Gene replacement using viral and non-viral methods of delivery to cells has been replaced by genome editing using programmable nucleases used both in vitro and in vivo.

Rational Design of ssODN to Correct Mutations by Gene Editing.

Gene editing allows to make a variety of targeted changes in genome, which can potentially be used to treat hereditary human diseases. Despite numerous studies in this area, effectiveness of gene editing methods for correcting mutations is still low, so these methods are not allowed in routine practice. It has been shown that rational design of genome editing components can significantly increase efficiency of mutation correction.

Oil spills in the Barents Sea: The results of multiyear monitoring with synthetic aperture radar.

This paper presents the results of multiyear satellite monitoring of oil pollution in the Barents Sea conducted in 2015-2020. Monitoring was based on synthetic aperture radar (SAR) images from the European Space Agency's Sentinel-1A and Sentinel-1B satellites. During monitoring, more than 26,000 SAR images were collected and analyzed for oil pollution in the form of oil spills.

Influence of Copper Oxide Nanoparticles on Gene Expression of Birch Clones In Vitro under Stress Caused by Phytopathogens.

Recently, metal oxide nanoparticles (NPs) have attracted attention as promising components for the protection and stimulation of plant microclones in tissue culture in vitro. However, the effect of NPs on the genetic mechanisms underlying plant adaptive responses remains poorly understood. We studied the effect of column-shaped CuO NPs 50 nm in diameter and 70-100 nm in length at a concentration of 0.

Oxidative Damage of Proteins Precedes Loss of Cholinergic Phenotype in the Septal Neurons of Olfactory Bulbectomized Mice.

Background: The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer's disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer's disease.

Objective: Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model.

Keratins as an Inflammation Trigger Point in Epidermolysis Bullosa Simplex.

Epidermolysis bullosa simplex (EBS) is a group of inherited keratinopathies that, in most cases, arise due to mutations in keratins and lead to intraepidermal ruptures. The cellular pathology of most EBS subtypes is associated with the fragility of the intermediate filament network, cytolysis of the basal layer of the epidermis, or attenuation of hemidesmosomal/desmosomal components. Mutations in keratins 5/14 or in other genes that encode associated proteins induce structural disarrangements of different strengths depending on their locations in the genes.

hTERT-Driven Immortalization of RDEB Fibroblast and Keratinocyte Cell Lines Followed by Cre-Mediated Transgene Elimination.

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a crippling disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Using ectopic expression of hTERT/hTERT + BMI-1 in primary cells, we developed expansible cultures of RDEB fibroblasts and keratinocytes. We showed that they display the properties of their founders, including morphology, contraction ability and expression of the respective specific markers including reduced secretion of type VII collagen (C7).

Immortalization of Human Keratinocytes Using the Catalytic Subunit of Telomerase.

A new stable line of human keratinocytes was obtained. The cells have altered morphology, both abnormal chromosomal composition and expression of keratinocyte markers, do not show contact inhibition, could be cultured in various media and have limited stratification ability in vitro. Upon transplantation into nude mice the cells have tumorigenic properties.

Signatures of Dermal Fibroblasts from RDEB Pediatric Patients.

The recessive form of dystrophic epidermolysis bullosa (RDEB) is a debilitating disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Mutations in the COL7A1 gene induce multiple abnormalities, including chronic inflammation and profibrotic changes in the skin. However, the correlations between the specific mutations in COL7A1 and their phenotypic output remain largely unexplored.

[Certain characteristics of the perinatal development of children whose parents were exposed to the action of uranium fission products].

Analysis was made of the character of the perinatal development of 238 children. In 65 of these, the parents were exposed to the action of uranium fission products in the basin of the river Techa in the Chelyabinsk region. The parents were radiated approximately 5 years before the children's birth.

[Activation of processes of perception and visual memory in teaching pathological anatomy].

The comparative study of different methods of student work with macroscopical preparations and different variants of slides presentation is performed. The volume of the demonstrative material reproduction was checked one week after the presentation. It was required to list in a control card a full name of macro- and microscopical preparations presented.

[Early detection of ovarian cancer].

The authors have analysed the results of the diagnosis and treatment in 144 patients with ovarian cancer, which took second place (28.8%) among malignant diseases of female gneitalia. Including in ovarian cancer high-risk group of females with impaired menstrual cycle and reproduction function, previously subjected to surgery on the adnexa, mammary glands, the intestine and also of those longterm followed up for uterine tumors and their detailed examination would contribute to earlier establishment of the diagnosis of ovarian cancer and enabled the percentage of far-advanced cases of the affection to be reliably reduced in 1974-75, and a percentage of clinical recovery to be increased in ovarian cancer patients to the moment of their discharge.

[Carbon dioxide fixation in aquatic animals and its metabolic significance].

In experiments on the carp Cyprinus carpio and freshwater lamellibranch mollusc Anodonta cygnea, tissue and organ peculiarities of carboxylic reactions have been revealed together with their relationship to the temperatute and ionic composition of the incubation medium. It was shown that in fish the highest intensity of fixation of CO2 is exhibited by glandular organs with biosynthetic profile of the metabolism (liver), whereas in molluscs it is exhibited in the mantle which plays the key role in the formation of the shell, containing carbonate compounds of calcium.

[Intensity of carbon dioxide fixation in the tissues of carp depending on the environmental temperature].

According to the level of carbon dioxide fixation at the incubation temperature at 20 degrees C the organs under study are arranged as follows: liver, kidneys, glandular system of gills, spleen, myocardium, gastrointestinal tract, skeletal muscles. 20 degrees C is the most optimal temperature for the processes of carboxylation in the fish.