Prevalence of AZFс Y chromosome microdeletions and association with spermatogenesis in Russian men from the general population.

The Y chromosome contains a set of genes with testis-specific expression that are responsible for the development of testes and spermatogenesis, and it is the most important target in the search for genetic causes of male infertility. Most of these genes are located in the "azoospermia factor" AZF locus (regions AZFa, AZFb, and AZFc) on the long arm of the Y chromosome. Microdeletions of the Y chromosome, leading to the removal of the entire AZF locus as well as one or more regions (complete deletions), are one of the leading causes of spermatogenesis impairment and infertility.

Effect of Drug-to-Protein Reaction Kinetics on the Results of Thermal Proteome Profiling.

In this Letter, a two-term formalism for constructing protein solubility curves in thermal proteome profiling (TPP) is considered, which takes into account the efficiency of the drug-protein binding reaction. When the reaction is incomplete, this results in distortion of the otherwise sigmoidal shape of the curve after drug treatment, which is often observed in experiments. This distortion may be significant enough to disqualify the corresponding protein from the list of drug target candidates, thus negatively affecting the results of TPP data analysis.

Enhancing the reverse transcriptase function in Taq polymerase via AI-driven multiparametric rational design.

Introduction: Modification of natural enzymes to introduce new properties and enhance existing ones is a central challenge in bioengineering. This study is focused on the development of Taq polymerase mutants that show enhanced reverse transcriptase (RTase) activity while retaining other desirable properties such as fidelity, 5'- 3' exonuclease activity, effective deoxyuracyl incorporation, and tolerance to locked nucleic acid (LNA)-containing substrates. Our objective was to use AI-driven rational design combined with multiparametric wet-lab analysis to identify and validate Taq polymerase mutants with an optimal combination of these properties.

Suppression without Thawing: Constraining Structure Formation and Dark Energy with Galaxy Clustering.

We present a new perturbative full-shape analysis of BOSS galaxy clustering data, including the full combination of the galaxy power spectrum and bispectrum multipoles, baryon acoustic oscillations, and cross-correlations with the gravitational lensing of cosmic microwave background measured from Planck. Assuming the ΛCDM model, we constrain the matter density fraction Ω_{m}=0.3138±0.

[The role of immuno-inflammatory factors in the development of negative symptoms in schizophrenia].

The literature review assessed the data obtained over the past 10 years on the relationship between inflammatory markers and the severity of negative symptoms in schizophrenia. A systematic search of the PubMed, Mendeley, and eLibrary databases was conducted in accordance with the PRISMA guidelines. Of the 407 publications found, 7 studies were selected by keywords that quantitatively assessed the relationship between the concentration of inflammatory markers and the severity of negative disorders in schizophrenia.

Positive Effects of Argon Inhalation After Traumatic Brain Injury in Rats.

The noble gas argon is one of the most promising neuroprotective agents for hypoxic-reperfusion injuries of the brain. However, its effect on traumatic injuries has been insufficiently studied. The aim of this study was to analyze the effect of the triple inhalation of the argon-oxygen mixture Ar 70%/O 30% on physical and neurological recovery and the degree of brain damage after traumatic brain injury and to investigate the possible molecular mechanisms of the neuroprotective effect.

Enhancing genetic discovery through narrow phenotyping in schizophrenia.

Background: Schizophrenia varies greatly from person to person, mainly because of its polygenic nature. Consequently, schizophrenia patients form distinct subphenotypes of schizophrenia, with specific symptom patterns and outcomes.

Methods: This study included 4257 adults, with long-term schizophrenia (control - 8955 individuals) who were assessed for schizophrenia with potentially severe outcomes based on following criteria: disability in functional and/or physical domains before the age of 40; severe negative symptoms (present in infancy or shortly after onset); a continuous course of the disease.

A probable ancient nearshore zone in southern Utopia on Mars unveiled from observations at the Zhurong landing area.

The Chinese Mars rover Zhurong successfully landed in southern Utopia Planitia on Mars in May 2021. Previous research suggested a Hesperian ocean may have existed in the northern lowland on Mars. Recent research observed water-related features at the Zhurong landing site from in situ data.

Chiral topological light for detection of robust enantiosensitive observables.

The topological response of matter to electromagnetic fields is a highly demanded property in materials design and metrology due to its robustness against noise and decoherence, stimulating recent advances in ultrafast photonics. Embedding topological properties into the enantiosensitive optical response of chiral molecules could therefore enhance the efficiency and robustness of chiral optical discrimination. Here we achieve such a topological embedding by introducing the concept of chiral topological light-a light beam which displays chirality locally, with an azimuthal distribution of its handedness described globally by a topological charge.

Citrus flavonoids diosmin, myricetin and neohesperidin as inhibitors of Pseudomonas aeruginosa: Evidence from antibiofilm, gene expression and in vivo analysis.

Citrus flavonoids are group of bioactive polyphenols. Here, we investigated the potential of diosmin, myricetin and neohesperidin as possible inhibitors of Pseudomonas aeruginosa. This bacterium is a major clinical challenge due to its propensity to form resistant biofilm.

[A clinical case of reverse left ventricular remodeling in patient with pathogenic TTN mutation. Case report].

Dilated cardiomyopathy (DCM) is a leading cause of heart failure, sudden cardiac death, and heart transplantation in young patients. The causes of DCM are varied and include genetic factors and metabolic, infectious, toxic and others factors. Today it is known that germline mutations in more than 98 genes can be associated with the occurrence of DCM.

Tackling APOE's structural challenges via in silico modeling in the era of neural networks: Can AlphaFold II help circumvent the problem of lacking full-length protein structure?

The APOE gene, encoding apolipoprotein E, is a predictor of longevity and age-related diseases. Despite numerous genetic studies, the data on molecular mechanisms by which apolipoprotein E affects the human phenotype remain incomplete due to the structural properties of the protein. Recently, a number of studies have used in silico drug discovery techniques based on protein-ligand docking, further highlighting the issue of lacking 3D structure of apolipoprotein E.

Application of concentration-weighted trajectory approach to identify sources with high anthropogenic mercury emissions in the East Asia.

The study evaluates the applicability of the CWT method for identifying mercury sources in a region with high anthropogenic emissions. Analysis is conducted to compare results on grids of 1 × 1°, 0.5 × 0.

The Low-Income and Middle-Income Countries' Perspective on Global Neurosurgery Collaborations.

Background And Objectives: Access to neurosurgical care is limited in low-income and middle-income countries (LMICs) and in marginalized communities in high-income countries (HICs). International partnerships represent one possible means of addressing this issue. Insights from surgeons in HICs have been explored, but data from LMICs' counterparts are scarce.

Evaluation of blood MSI burden dynamics to trace immune checkpoint inhibitor therapy efficacy through the course of treatment.

Analysis of serial liquid biopsy (LB) samples has been found to be a promising approach for the monitoring of tumor dynamics in the course of therapy for patients with colorectal cancer (CRC). Currently, somatic mutations are used for tracing the dynamics of the tumor via LB. However, the analysis of the dynamic changes in the molecular signatures such as microsatellite instability (MSI) is not currently used.

Multi-Institutional Evaluation of Interrater Agreement of Biomarker-Drug Pair Rankings Based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) and Sources of Discordance.

Background: The widespread use of next-generation sequencing in clinical practice has contributed to the accumulation of a large number of genomic findings associated with targeted therapy; therefore, the problem of ranking the detected findings has become acute. The European Society for Medical Oncology Scale of Clinical Actionability of molecular Targets (ESCAT) system was designed by the European Society for Medical Oncology to rank biomarkers into levels of evidence that reflect their potency and clinical significance based on published clinical data. However, the ESCAT system remains imperfect, as it is based on a subjective assessment of the levels of evidence.

Simultaneous Visualization of R-Loops/RNA:DNA Hybrids and Replication Forks in a DNA Combing Assay.

R-loops, structures that play a crucial role in various biological processes, are integral to gene expression, the maintenance of genome stability, and the formation of epigenomic signatures. When these R-loops are deregulated, they can contribute to the development of serious health conditions, including cancer and neurodegenerative diseases. The detection of R-loops is a complex process that involves several approaches.

Subcycle dynamics of excitons under strong laser fields.

Excitons play a key role in the linear optical response of two-dimensional (2D) materials. However, their role in the nonlinear response to intense, nonresonant, low-frequency light is often overlooked as strong fields are expected to tear the electron-hole pair apart. Using high-harmonic generation as a spectroscopic tool, we theoretically study their formation and role in the nonlinear optical response.

Autoencoder latent space sensitivity to material structure in convergent-beam low energy electron diffraction.

The convergent-beam low energy electron diffraction technique has been proposed as a novel method to gather local structural and electronic information from crystalline surfaces during low-energy electron microscopy. However, the approach suffers from high complexity of the resulting diffraction patterns. We show that Convolutional Autoencoders trained on CBLEED patterns achieve a highly structured latent space.

Bidirectional Cascaded Superfluorescent Lasing in Air Enabled by Resonant Third Harmonic Photon Exchange from Nitrogen to Argon.

Cavity-free lasing in atmospheric air has stimulated intense research toward a fundamental understanding of underlying physical mechanisms. In this Letter, we identify a new mechanism-a third-harmonic photon mediated resonant energy transfer pathway leading to population inversion in argon via an initial three-photon excitation of nitrogen molecules irradiated by intense 261 nm pulses-that enables bidirectional two-color cascaded lasing in atmospheric air. By making pump-probe measurements, we conclusively show that such cascaded lasing results from superfluorescence rather than amplified spontaneous emission.

Observation of Medium-Induced Yield Enhancement and Acoplanarity Broadening of Low-p_{T} Jets from Measurements in pp and Central Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high p_{T}) hadron trigger in proton-proton and central Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb-Pb collisions.

Failure of immune checkpoint inhibitors for microsatellite instability-positive pancreatic adenocarcinoma with atypical pattern of short tandem repeat mutation.

Microsatellite instability (MSI) is an important biomarker in cancer. While routine methods can detect MSI in certain tumor types, in other tumor types the results may be incorrect due to differences in the MSI loci pattern. Here, we report the case of a patient with pancreatic adenocarcinoma, with confirmed MSI by two independent next-generation sequencing tests, but not by routine methods, who had progression on pembrolizumab.