Novel Synonymous HLA-B*35:01:80 Allele Identified by Next-Generation Sequencing.

The new HLA-B*35:01:80 allele showed one synonymous nucleotide difference compared to the HLA-B*35:01:01:01 allele in codon 137.

WES-based screening of 7,000 newborns: A pilot study in Russia.

The effective implementation of whole-exome sequencing- and whole-genome sequencing-based diagnostics in the management of children affected with genetic diseases and the rapid decrease in the cost of next-generation sequencing (NGS) enables the expansion of this method to newborn genetic screening programs. Such NGS-based screening greatly increases the number of diseases that can be detected compared to conventional newborn screening, as the latter is aimed at early detection of a limited number of inborn diseases. Moreover, genetic testing provides new possibilities for family members of the proband, as many variants responsible for adult-onset conditions are inherited from the parents.

Plasmonic nano-aperture label-free imaging of single small extracellular vesicles for cancer detection.

Background: Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling.

Methods: In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis.

ANPEP/CD13 Expression as a Marker of Lymphovascular Invasion and Survival in Esophageal Adenocarcinoma.

Background: The presence of lymphovascular invasion (LVI) in early esophageal adenocarcinoma (EAC) is associated with more aggressive disease. Molecular markers associated with LVI are still largely unknown. Using a combination of transcriptomic analysis and validation experiments, we sought to describe markers for LVI and survival.

Passive Microwave Radiometry and microRNA Detection for Breast Cancer Diagnostics.

Breast cancer prevention is an important health issue for women worldwide. In this study, we compared the conventional breast cancer screening exams of mammography and ultrasound with the novel approaches of passive microwave radiometry (MWR) and microRNA (miRNA) analysis. While mammography screening dynamics could be completed in 3-6 months, MWR provided a prediction in a matter of weeks or even days.

Contribution of the Collective Excitations to the Coupled Proton and Energy Transport along Mitochondrial Cristae Membrane in Oxidative Phosphorylation System.

The results of many experimental and theoretical works indicate that after transport of protons across the mitochondrial inner membrane (MIM) in the oxidative phosphorylation (OXPHOS) system, they are retained on the membrane-water interface in nonequilibrium state with free energy excess due to low proton surface-to-bulk release. This well-established phenomenon suggests that proton trapping on the membrane interface ensures vectorial lateral transport of protons from proton pumps to ATP synthases (proton acceptors). Despite the key role of the proton transport in bioenergetics, the molecular mechanism of proton transfer in the OXPHOS system is not yet completely established.

Evaluation of therapeutic strategies targeting BCAA catabolism using a systems pharmacology model.

Abnormal branched-chained amino acids (BCAA) accumulation in cardiomyocytes is associated with cardiac remodeling in heart failure. Administration of branched-chain α-keto acid dehydrogenase (BCKD) kinase inhibitor BT2 has been shown to reduce cardiac BCAA levels and demonstrated positive effects on cardiac function in a preclinical setting. The current study is focused on evaluating the impact of BT2 on the systemic and cardiac levels of BCAA and their metabolites as well as activities of BCAA catabolic enzymes using a quantitative systems pharmacology model.

Diagnostics of Ovarian Tumors in Postmenopausal Patients.

Early diagnosis of ovarian cancer remains an urgent issue owing to the continuing trend towards increasing incidence along with only marginal improvements in mortality and 5-year survival rates. Furthermore, there is a lack of a clear formulation of the concept of pathogenesis. The diagnostic values of tumor markers, their potential advantages and disadvantages, and their combination with radiation imaging methods and transvaginal sonography are discussed.

Three Grand Challenges in High Throughput Omics Technologies.

Over the years, next-generation sequencing (NGS) and advanced bioinformatics approaches have allowed the transition of genomic assays into translational practices [...

Collective excitations in α-helical protein structures interacting with the water environment.

Low-frequency vibrational excitations of protein macromolecules in the terahertz frequency region are suggested to contribute to many biological processes such as enzymatic catalysis, intra-protein energy/charge transport, recognition, and allostery. To explain high effectiveness of these processes, two possible mechanisms of the long-lived excitation were proposed by H. Fröhlich and A.

Cycle Network Model of Prostaglandin H Synthase-1.

The kinetic model of Prostaglandin H Synthase-1 (PGHS-1) was developed to investigate its complex network kinetics and non-steroidal anti-inflammatory drugs (NSAIDs) efficacy in different in vitro and in vivo conditions. To correctly describe the complex mechanism of PGHS-1 catalysis, we developed a microscopic approach to modelling of intricate network dynamics of 35 intraenzyme reactions among 24 intermediate states of the enzyme. The developed model quantitatively describes interconnection between cyclooxygenase and peroxidase enzyme activities; substrate (arachidonic acid, AA) and reducing cosubstrate competitive consumption; enzyme self-inactivation; autocatalytic role of AA; enzyme activation threshold; and synthesis of intermediate prostaglandin G (PGG) and final prostaglandin H (PGH) products under wide experimental conditions.

Prenatal diagnosis of Prader-Willi syndrome due to uniparental disomy with NIPS: Case report and literature review.

Background: PWS is challenging to diagnose prenatally due to a lack of precise and well-characterized fetal phenotypes and noninvasive markers. Here we present the case of prenatal diagnosis of Prader-Willi syndrome, which was suspected with whole-genome NIPS.

Methods: Whole-genome noninvasive prenatal screening showed a high risk for trisomy 15.

gen. nov., sp. nov. isolated from human faeces.

A strain of obligately anaerobic, spore-forming, Gram-positive rods was isolated from child faeces and characterized both phenotypically and genotypically. Phylogenetic analysis based on 16S rRNA gene and whole genome sequencing revealed the strain to represent a member of the family distant from described species and genera. The strain was moderately saccharolytic with mannose as the preferred substrate and produced lactic acid, acetic acid and H as the end products.

Multimodal Optical Diagnostics of the Microhaemodynamics in Upper and Lower Limbs.

The introduction of optical non-invasive diagnostic methods into clinical practice can substantially advance in the detection of early microcirculatory disorders in patients with different diseases. This paper is devoted to the development and application of the optical non-invasive diagnostic approach for the detection and evaluation of the severity of microcirculatory and metabolic disorders in rheumatic diseases and diabetes mellitus. The proposed methods include the joint use of laser Doppler flowmetry, absorption spectroscopy and fluorescence spectroscopy in combination with functional tests.

Epigenetic-genetic chromatin footprinting identifies novel and subject-specific genes active in prefrontal cortex neurons.

Human prefrontal cortex (PFC) is associated with broad individual variabilities in functions linked to personality, social behaviors, and cognitive functions. The phenotype variabilities associated with brain functions can be caused by genetic or epigenetic factors. The interactions between these factors in human subjects is, as of yet, poorly understood.

Outcomes after endoscopic mucosal resection or esophagectomy for submucosal esophageal adenocarcinoma.

Objectives: Endoscopic mucosal resection (EMR) is a diagnostic and potentially therapeutic option for patients with submucosal esophageal adenocarcinoma. However, there are significant concerns regarding the risk of lymph node metastasis. Our purpose was to construct a comparative effectiveness analysis comparing recurrence patterns after therapeutic EMR or esophagectomy.

Noncontiguous finished genome sequence of sp. ASD88, isolated from faeces of a child with autism spectrum disorder.

We report here a draft genome sequence of sp. ASD88, a strain from the intestinal microbiota of a child with autism spectrum disorder, representing a previously undescribed species of the genus The assembled sequence consists of 88 scaffolds, and the total size is 2.59 Mb.

Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults.

Background: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown.

Objective: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood.

Methods: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age.

Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling physiologically-relevant activities from those associated with Alzheimer's disease.

The intramembrane proteolytic activities of presenilins (PSEN1/PS1 and PSEN2/PS2) underlie production of β-amyloid, the key process in Alzheimer's disease (AD). Dysregulation of presenilin-mediated signaling is linked to cancers. Inhibition of the γ-cleavage activities of PSENs that produce Aβ, but not the ε-like cleavage activity that release physiologically essential transcription activators, is a potential approach for the development of rational therapies for AD.

In silico size selection is effective in reducing false positive NIPS cases of monosomy X that are due to maternal mosaic monosomy X.

Objectives: The aim of this study was to establish maternal contribution to false positive noninvasive prenatal DNA screening (NIPS) results and develop the method to distinguish maternal and fetal origin of high-risk monosomy X NIPS calls including mosaic maternal cases.

Method: A total of 906 women carrying singleton pregnancies have been recruited. Maternal plasma DNA semiconductor massive parallel sequencing was performed to detect common aneuploidies.