[Treatment of primary malignant melanoma of the esophagus].

Objective: To present treatment of primary esophageal melanoma in a young patient, as well as review of modern data on this issue.

Material And Methods: We describe the results of treatment of a patient with primary melanoma of the esophagus. PubMed, SCOPUS, and elibrary databases were used for the review.

Troponin Structural Dynamics in the Native Cardiac Thin Filament Revealed by Cryo Electron Microscopy.

Cardiac muscle contraction occurs due to repetitive interactions between myosin thick and actin thin filaments (TF) regulated by Ca levels, active cross-bridges, and cardiac myosin-binding protein C (cMyBP-C). The cardiac TF (cTF) has two nonequivalent strands, each comprised of actin, tropomyosin (Tm), and troponin (Tn). Tn shifts Tm away from myosin-binding sites on actin at elevated Ca levels to allow formation of force-producing actomyosin cross-bridges.

Gene Mutations: Implications for Hereditary Cancer Syndromes.

Malignant neoplasms, including pancreatic cancer and melanoma, are major global health challenges. This study investigates melanoma pancreatic syndrome, a rare hereditary tumor syndrome associated with gene mutations. mutations contribute to a lifetime risk of melanoma ranging from 28% to 67%.

[The structure of pathogenic germline variants in colorectal cancer in Moscow patients].

Objective: Describe the structure of pathogenic germline variants and clinical and anatomical features in colorectal cancer patients in Moscow.

Material And Methods: The whole genome sequencing results of patients with suspected hereditary cancer syndrome were evaluated. All identified genetic variants were validated using Sanger sequencing.

[Anatomical resection for non-small cell lung cancer: cardiopulmonary exercise testing in assessing the risk of respiratory complications].

Objective: To assess the role of cardiopulmonary exercise testing in examination of patients with high risk of respiratory complications in anatomical resections for non-small cell lung cancer.

Material And Methods: A non-randomized retrospective single-center study was devoted to immediate results of surgical treatment of patients with NSCLC between December 2020 and April 2021. Median age of patients was 65 (84; 30) years, male-to-female ratio - 129 (57%)/98 (43%).

Cardiac troponin T N-domain variant destabilizes the actin interface resulting in disturbed myofilament function.

Missense variant Ile79Asn in human cardiac troponin T (cTnT-I79N) has been associated with hypertrophic cardiomyopathy and sudden cardiac arrest in juveniles. cTnT-I79N is located in the cTnT N-terminal (TnT1) loop region and is known for its pathological and prognostic relevance. A recent structural study revealed that I79 is part of a hydrophobic interface between the TnT1 loop and actin, which stabilizes the relaxed (OFF) state of the cardiac thin filament.

The Gene Germline Heterozygous Pathogenic Variants in Russian Patients with Malignant Neoplasms and Healthy Carriers: 11,800 WGS Results.

More than 275 million people in the world are carriers of a heterozygous mutation of the gene, associated with cystic fibrosis, the most common autosomal recessive disease among Caucasians. Some recent studies assessed the association between carriers of variants and some pathologies, including cancer risk. The aim of this study is to analyze the landscape of germline pathogenic heterozygous variants in patients with diagnosed malignant neoplasms.

High-resolution cryo-EM structure of the junction region of the native cardiac thin filament in relaxed state.

Cardiac contraction depends on molecular interactions among sarcomeric proteins coordinated by the rising and falling intracellular Ca levels. Cardiac thin filament (cTF) consists of two strands composed of actin, tropomyosin (Tm), and equally spaced troponin (Tn) complexes forming regulatory units. Tn binds Ca to move Tm strand away from myosin-binding sites on actin to enable actomyosin cross-bridges required for force generation.

Investigation of the Technological Possibility of Manufacturing Volumetric Shaped Ductile Cast Iron Products in Open Dies.

Information about the technological possibility of stamping in open dies, round-shaped forgings made of ductile cast iron, is outlined herein. Cast iron's propensity for plastic deformation under complex loading conditions is analyzed from the standpoint of the morphology of graphite inclusions, depending on the degree and mechanical scheme of deformation. The research methodology included: the choice of a brand of cast iron with spherical graphite and the technological process of its deformation; mathematical modeling of the deformation process using the DEFORM-3D software package; stamping of an experimental batch of forgings; and microstructural studies of the forging material, together with the data of its stress-strain state and the direction of flow of the material.

[Fast track recovery protocols for extended pelvic surgery].

Objective: To compare the immediate results of extended pelvic surgery before and after introduction of standardized fast track surgery (FTS) protocol into routine clinical practice.

Material And Methods: The study included 111 patients with pelvic tumors who underwent extended pelvic surgery. The control group included 59 patients whose perioperative management implied traditional approaches (2018-2019), the main group - 52 patients with FTS protocol (2020-2021).

Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.

Cardiac myosin binding protein C (cMyBP-C) modulates cardiac contraction via direct interactions with cardiac thick (myosin) and thin (actin) filaments (cTFs). While its C-terminal domains (e.g.

Actomyosin Complex.

Formation of cross-bridges between actin and myosin occurs ubiquitously in eukaryotic cells and mediates muscle contraction, intracellular cargo transport, and cytoskeletal remodeling. Myosin motors repeatedly bind to and dissociate from actin filaments in a cycle that transduces the chemical energy from ATP hydrolysis into mechanical force generation. While the general layout of surface elements within the actin-binding interface is conserved among myosin classes, sequence divergence within these motifs alters the specific contacts involved in the actomyosin interaction as well as the kinetics of mechanochemical cycle phases.

Ca attenuates nucleation activity of leiomodin.

A transient increase in Ca concentration in sarcomeres is essential for their proper function. Ca drives striated muscle contraction via binding to the troponin complex of the thin filament to activate its interaction with the myosin thick filament. In addition to the troponin complex, the myosin essential light chain and myosin-binding protein C were also found to be Ca sensitive.

[Clinical efficacy of ct-guided transthoracic needle biopsy of peripheral lung lesions].

Objective: To evaluate the effectiveness of a step-by-step protocol for GT-guided transthoracic biopsy in verification of peripheral lung tumors.

Material And Methods: A retrospective analysis of the results of GT-guided transthoracic biopsies of focal lung neoplasms was performed between October 2019 and December 2020. The analysis included the results of 176 biopsies in 158 patients.

Optimization of small extracellular vesicle isolation from expressed prostatic secretions in urine for in-depth proteomic analysis.

The isolation and subsequent molecular analysis of extracellular vesicles (EVs) derived from patient samples is a widely used strategy to understand vesicle biology and to facilitate biomarker discovery. Expressed prostatic secretions in urine are a tumor proximal fluid that has received significant attention as a source of potential prostate cancer (PCa) biomarkers for use in liquid biopsy protocols. Standard EV isolation methods like differential ultracentrifugation (dUC) co-isolate protein contaminants that mask lower-abundance proteins in typical mass spectrometry (MS) protocols.

[Enhanced recovery in thoracic surgery].

Objective: To present an experience of adapting the accelerated rehabilitation protocol at the thoracic surgery department of the Moscow City Clinical Oncology Hospital No. 1.

Material And Methods: An effectiveness of the accelerated rehabilitation program in the city oncology hospital was retrospectively analyzed for the period from February to December 2019.

Interaction of the C2 Ig-like Domain of Cardiac Myosin Binding Protein-C with F-actin.

Cardiac muscle contraction depends on interactions between thick (myosin) and thin (actin) filaments (TFs). TFs are regulated by intracellular Ca levels. Under activating conditions Ca binds to the troponin complex and displaces tropomyosin from myosin binding sites on the TF surface to allow actomyosin interactions.

Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy.

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca-regulation of myocardial contraction. Here, we report the molecular basis of a human mutation in cTnC's αD-helix (-p.C84Y) that impacts conformational dynamics of the D/E central-linker and sampling of discrete states in the N-domain, favoring the "primed" state associated with Ca binding.

The structure of the native cardiac thin filament at systolic Ca levels.

Every heartbeat relies on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising and falling Ca levels. Thin filaments are comprised of two actin strands, each harboring equally separated troponin complexes, which bind Ca to move tropomyosin cables away from the myosin binding sites and, thus, activate systolic contraction. Recently, structures of thin filaments obtained at low (pCa ∼9) or high (pCa ∼3) Ca levels revealed the transition between the Ca-free and Ca-bound states.

High-Resolution Cryo-EM Structure of the Cardiac Actomyosin Complex.

Heart contraction depends on a complicated array of interactions between sarcomeric proteins required to convert chemical energy into mechanical force. Cyclic interactions between actin and myosin molecules, controlled by troponin and tropomyosin, generate the sliding force between the actin-based thin and myosin-based thick filaments. Alterations in this sophisticated system due to missense mutations can lead to cardiovascular diseases.

Effects of cardiomyopathy-linked mutations K15N and R21H in tropomyosin on thin-filament regulation and pointed-end dynamics.

Missense mutations K15N and R21H in striated muscle tropomyosin are linked to dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), respectively. Tropomyosin, together with the troponin complex, regulates muscle contraction and, along with tropomodulin and leiomodin, controls the uniform thin-filament lengths crucial for normal sarcomere structure and function. We used Förster resonance energy transfer to study effects of the tropomyosin mutations on the structure and kinetics of the cardiac troponin core domain associated with the Ca-dependent regulation of cardiac thin filaments.

N-Terminal Domains of Cardiac Myosin Binding Protein C Cooperatively Activate the Thin Filament.

Muscle contraction relies on interaction between myosin-based thick filaments and actin-based thin filaments. Myosin binding protein C (MyBP-C) is a key regulator of actomyosin interactions. Recent studies established that the N'-terminal domains (NTDs) of MyBP-C can either activate or inhibit thin filaments, but the mechanism of their collective action is poorly understood.

Accurate flexible refinement of atomic models against medium-resolution cryo-EM maps using damped dynamics.

Background: Dramatic progress has recently been made in cryo-electron microscopy technologies, which now make possible the reconstruction of a growing number of biomolecular structures to near-atomic resolution. However, the need persists for fitting and refinement approaches that address those cases that require modeling assistance.

Methods: In this paper, we describe algorithms to optimize the performance of such medium-resolution refinement methods.

Characterization and Evidence of the miR-888 Cluster as a Novel Cancer Network in Prostate.

Prostate cancer afflicts 1 in 7 men and is the second leading cause of male cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive class of approximately 22 nucleotide noncoding RNAs, are often aberrantly expressed in tissues and fluids from prostate cancer patients, but the mechanisms of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly understood. Here, miR-888 was identified as a novel prostate factor that promotes proliferation and migration.