Desmin mutations impact the autophagy flux in C2C12 cell in mutation-specific manner.

Desmin is the main intermediate filament of striated and smooth muscle cells and plays a crucial role in maintaining the stability of muscle fiber during contraction and relaxation cycles. Being a component of Z-disk area, desmin integrates autophagic pathways, and the disturbance of Z-disk proteins' structure negatively affects chaperone-assisted selective autophagy (CASA). In the present study, we focused on alteration of autophagy flux in myoblasts expressing various Des mutations.

Dynamic NIR Fluorescence Imaging and Machine Learning Framework for Stratifying High vs. Low Notch-Dll4 Expressing Host Microenvironment in Triple-Negative Breast Cancer.

Delta like canonical notch ligand 4 (Dll4) expression levels in tumors are known to affect the efficacy of cancer therapies. This study aimed to develop a model to predict Dll4 expression levels in tumors using dynamic enhanced near-infrared (NIR) imaging with indocyanine green (ICG). Two rat-based consomic xenograft (CXM) strains of breast cancer with different Dll4 expression levels and eight congenic xenograft strains were studied.

The HUSH complex controls brain architecture and protocadherin fidelity.

The HUSH (human silencing hub) complex contains the H3K9me3 binding protein M-phase phosphoprotein 8 (MPP8) and recruits the histone methyltransferase SETDB1 as well as Microrchidia CW-type zinc finger protein 2 (MORC2). Functional and mechanistic studies of the HUSH complex have hitherto been centered around SETDB1 while the in vivo functions of MPP8 and MORC2 remain elusive. Here, we show that genetic inactivation of or in the nervous system of mice leads to increased brain size, altered brain architecture, and behavioral changes.

Rare clinical phenotype of filaminopathy presenting as restrictive cardiomyopathy and myopathy in childhood.

Background: FLNC is one of the few genes associated with all types of cardiomyopathies, but it also underlies neuromuscular phenotype. The combination of concomitant neuromuscular and cardiac involvement is not often observed in filaminopathies and the impact of this on the disease prognosis has hitherto not been analyzed.

Results: Here we provide a detailed clinical, genetic, and structural prediction analysis of distinct FLNC-associated phenotypes based on twelve pediatric cases.

Case Report: Two New Cases of Autosomal-Recessive Hypertrophic Cardiomyopathy Associated With -Compound Heterozygous Variant.

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary diseases, and it is associated with fatal complications. The clinical heterogeneity of HCM requires risk prediction models to identify patients at a high risk of adverse events. Most HCM cases are caused by mutations in genes encoding sarcomere proteins.

Estimating correlations between vaccine clinical trial outcomes.

We demonstrate how a linear factor model with latent variables can be used to estimate correlations between the outcomes of clinical trials. These correlations are needed for many policy questions of drug/vaccine development (such as calculating the optimal size of financial incentives) and the literature so far has relied on expert opinions. We apply our methodology to the case of vaccines and show that the estimated correlations are highly significant.

Case Reports: Emery-Dreifuss Muscular Dystrophy Presenting as a Heart Rhythm Disorders in Children.

Emery-Dreifuss muscular dystrophy (EDMD) is inherited muscle dystrophy often accompanied by cardiac abnormalities in the form of supraventricular arrhythmias, conduction defects and sinus node dysfunction. Cardiac phenotype typically arises years after skeletal muscle presentation, though, could be severe and life-threatening. The defined clinical manifestation with joint contractures, progressive muscle weakness and atrophy, as well as cardiac symptoms are observed by the third decade of life.

ASSESSMENT OF CORRELATION BETWEEN MIRNAS-21-3P AND -210-3P EXPRESSION IN MATERNAL AND UMBILICAL CORD PLASMA AND FETAL WEIGHT AT BIRTH.

Objective: The aim: To determine the degree of correlation of mass of the fetus and the level of mir-21, mir210 in maternal blood and umbilical cord blood of the fetus in uncomplicated gestation.

Patients And Methods: Materials and methods: 60 pregnant women with a single baby pregnancy in the third trimester (37-40 weeks) were examined. They all were given a general clinical, obstetric and the level of miRNA21-3р and miRNA210-3р were determined in the whole blood of pregnant women (before labor) and in fetal blood obtained from the umbilical artery at birth.

Dual Color Imaging from a Single BF-Azadipyrromethene Fluorophore Demonstrated for Lymph Node Identification.

Dual emissions at ~700 and 800 nm have been achieved from a single NIR-AZA fluorophore by establishing parameters in which it can exist in either its isolated molecular or aggregated states. Dual near infrared (NIR) fluorescence color lymph node (LN) mapping with was achieved in a large-animal porcine model, with injection site, channels and nodes all detectable at both 700 and 800 nm using a preclinical open camera system. The fluorophore was also compatible with imaging using two clinical instruments for fluorescence guided surgery.

Maternal psychosocial stress and labor dystocia.

Objective: The aim: to study the possible role of psychosocial stressors in the emergence of anomalies of childbirth, as well as to examine their nature using the example of pregnant women who have been forcefully displaced from Donetsk and Luhansk regions of Ukraine.

Patients And Methods: Materials and methods: 115 internally displaced pregnant women from Donetsk and Luhansk regions, were surveyed. All women underwent a comprehensive neuropsychological examination of their psycho-emotional status via interviews, questioning, and psychological testing (Spielberg-Haning's Situational and Personal Anxiety Scale).

Pain as leading syndrome of the somatoform disorders at the pediatrics.

Objective: The aim: Study of somatoform vegetative dysfunction' clinical features at adolescent age with a chronic pain (HA syndrome and AP syndrome), and also socially-psychological factors of its formation too.

Patients And Methods: Materials and methods: There are 82 teenagers have been examined in this research: 48 girls (58,5 %) and 34 young men (41,5 %) at the age of 16 - 17 years. Research will be done according to diagnostic criteria of ICD-10.

Using Contrast Motion to Generate Patient-Specific Blood Flow Simulations During Invasive Coronary Angiography.

Virtual fractional flow reserve (vFFR) is an emerging technology employing patient-specific computational fluid dynamics (CFD) simulations to infer the hemodynamic significance of a coronary stenosis. Patient-specific boundary conditions are an important aspect of this approach and while most efforts make use of lumped parameter models to capture key phenomena, they lack the ability to specify the associated parameters on a patient-specific basis. When applying vFFR in a catheter laboratory setting using X-ray angiograms as the basis for creating the simulations, there is some indirect functional information available through the observation of the radio-opaque contrast agent motion.

Methods of transmission and features of the course of hepatitis c virus infection in children: medical and social aspects.

Objective: Introduction: Hepatitis C virus (HCV) infection is a major global problem. According to WHO, 150-200 million people globally have hepatitis C infection. Even though HCV infection morbidity rate in children is relatively low in comparison with the adult population, approximately 5 million children in the world have active HCV.

Monocytes with Oncogenic Mutation JAK2 V617F as a Tool for Studies of the Pathogenic Mechanisms of Myelofibrosis.

We analyzed previously generated stable monocyte-derived cell line carrying mutation JAK2 V617F. Evaluation of the expression of pro- and antifibrotic factors revealed changes in the production of MMPs and their inhibitors, growth factors, galectin-3, and pentraxin 3 in cells carrying mutation JAK2 in comparison with control non-modified cells.

CRISPR-UMI: single-cell lineage tracing of pooled CRISPR-Cas9 screens.

Pooled CRISPR screens are a powerful tool for assessments of gene function. However, conventional analysis is based exclusively on the relative abundance of integrated single guide RNAs (sgRNAs) between populations, which does not discern distinct phenotypes and editing outcomes generated by identical sgRNAs. Here we present CRISPR-UMI, a single-cell lineage-tracing methodology for pooled screening to account for cell heterogeneity.

A reversible haploid mouse embryonic stem cell biobank resource for functional genomics.

The ability to directly uncover the contributions of genes to a given phenotype is fundamental for biology research. However, ostensibly homogeneous cell populations exhibit large clonal variance that can confound analyses and undermine reproducibility. Here we used genome-saturated mutagenesis to create a biobank of over 100,000 individual haploid mouse embryonic stem (mES) cell lines targeting 16,970 genes with genetically barcoded, conditional and reversible mutations.

[Murine and human hematopoietic progenitor cultures grown on stromal layers expressing Notch ligands].

The ex vivo maintenance and expansion of hematopoietic stem cells and early progenitors is necessary for the successful treatment of hematopoietic and immune diseases. Multiple attempts to improve the expansion of hematopoietic stem cells (HSCs) by their cultivation in the presence of growth factor cocktails have so far failed. Novel approaches aimed at conserving the earliest precursors in their undifferentiated state are needed.

Impact of molybdenum out diffusion and interface quality on the performance of sputter grown CZTS based solar cells.

We have investigated the impact of CuZnSnS-Molybdenum (Mo) interface quality on the performance of sputter-grown CuZnSnS (CZTS) solar cell. Thin film CZTS was deposited by sputter deposition technique using stoichiometry quaternary CZTS target. Formation of molybdenum sulphide (MoS) interfacial layer is observed in sputter grown CZTS films after sulphurization.