Novel method for detection of Aβ and Iso-D7-Aβ N-terminus-specific B cells and Iso-D7-Aβ-specific antibodies.

Alzheimer's disease (AD) is a multifactorial systemic disease that is triggered, at least in part, by the accumulation of β-amyloid (Aβ) peptides in the brain, but it also depends on immune system-mediated regulation. Recent studies suggest that B cells may play a role in AD development and point to the accumulation of clonally expanded B cells in AD patients. However, the specificity of the clonally expanded B cells is unknown, and the contribution of Aβ-specific B cells to AD pathology development is unclear.

Survey of the Aβ-peptide structural diversity: molecular dynamics approaches.

Unlabelled: The review deals with the application of Molecular Dynamics (MD) to the structure modeling of beta-amyloids (Aβ), currently classified as intrinsically disordered proteins (IDPs). In this review, we strive to relate the main advances in this area but specifically focus on the approaches and methodology. All relevant papers on the Aβ modeling are cited in the Tables in Supplementary Data, including a concise description of the applied approaches, sorted according to the types of the studied systems: modeling of the monomeric Aβ and Aβ aggregates.

Blood plasma proteomic markers of Alzheimer's disease, current status and application prospects.

Introduction: Identifying early risks of developing Alzheimer's disease (AD) is a major challenge as the number of patients with AD steadily increases and requires innovative solutions. Current molecular diagnostic modalities, such as cerebrospinal fluid (CSF) testing and positron emission tomography (PET) imaging, exhibit limitations in their applicability for large-scale screening. In recent years, there has been a marked shift toward the development of blood plasma-based diagnostic tests, which offer a more accessible and clinically viable alternative for widespread use.

Selective retinoid X receptor agonism promotes functional recovery and myelin repair in experimental autoimmune encephalomyelitis.

Evidence that myelin repair is crucial for functional recovery in multiple sclerosis (MS) led to the identification of bexarotene (BXT). This clinically promising remyelinating agent activates multiple nuclear hormone receptor subtypes implicated in myelin repair. However, BXT produces unacceptable hyperlipidemia.

Strategies for automated affinity purification-resin screening for non-traditional biopharmaceuticals in the discovery space.

Biotherapeutics occupy a significant portion of the pharmaceutical pipeline and are projected to continue growing in sales and scope. Further, the field is advancing novel and more complex molecules beyond monoclonal antibodies including multi-target proteins, engineered proteins and bioconjugates. In this aspect, the development of increasingly advanced and challenging therapies necessitates a commiserate degree of innovation to develop automated methods for resin screening, purification, and analytics in the discovery space to quickly identify liabilities and rank candidates with minimal impact on developmental resources.

Structure of Full-Length Src Kinase and Its Key Phosphorylated States: Molecular Dynamics Study.

Src kinase is one of the key regulators of cellular metabolism and is dysregulated in numerous diseases, including cancer, neurodegenerative diseases, and particularly Alzheimer's disease. Despite its therapeutic importance, its full-length structure has never been obtained before, as it contains an intrinsically disordered regulatory region, SH4UD. The SH4UD region is crucial for Src activation, functional dimerization, and regulation by other kinases.

Endoscopic ultrasonography in diagnosis of chemical esophageal burn and prediction of cicatricial stenosis.

Objective: To analyze the role of endoscopic ultrasonography (EUS) in predicting the risk of cicatricial stenosis after chemical esophageal burn.

Material And Methods: A retrospective study included 56 patients with chemical esophageal burn grade III/IV. Primary endoscopy was performed upon admission.

Impact of Antioxidants on Mechanical Properties and ROS Levels of Neuronal Cells Exposed to β-Amyloid Peptide.

This study aims to investigate the potential role of antioxidants in oxidative stress and its consequent impact on the mechanical properties of neuronal cells, particularly the stress induced by amyloid-beta (1-42) (Aβ) aggregates. A key aspect of our research involved using scanning ion-conductance microscopy (SICM) to assess the mechanical properties (Young's modulus) of neuronal cells under oxidative stress. Reactive oxygen species (ROS) level was measured in single-cell using the electrochemical method by low-invasive Pt nanoelectrode.

Experimental-Modeling Framework for Identifying Defects Responsible for Reliability Issues in 2D FETs.

In this work, a self-consistent method is used to identify and describe defects plaguing 300 mm integrated 2D field-effect transistors. This method requires measurements of the transfer characteristic hysteresis combined with physics-based modeling of charge carrier capture and emission processes using technology computer aided design (TCAD) tools. The interconnection of experiments and simulations allows one to thoroughly characterize charge trapping/detrapping by/from defects, depending on their energy position.

Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals.

Background/objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue.

Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort.

Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples.

The Wound-Healing Effect of a Novel Fibroblasts-Impregnated Hydroxyethylcellulose Gel in a Rat Full-Thickness Burn Model: A Preclinical Study.

The objective of this study was to assess the efficacy of a cell-containing wound dressing based on fibroblasts in hydroxyethylcellulose (HEC) gel for the local treatment of deep partial-thickness and/or full-thickness skin burns in an animal model. The rats (male Wistar, n = 100) were subjected to a full-thickness thermal burn (16 cm). Radical necrectomy was performed one day after the burn.

β-Amyloids and Immune Responses Associated with Alzheimer's Disease.

Alzheimer's disease (AD) is associated with the accumulation of β-amyloids (Aβs) and the formation of Aβ plaques in the brain. Various structural forms and isoforms of Aβs that have variable propensities for oligomerization and toxicity and may differentially affect the development of AD have been identified. In addition, there is evidence that β-amyloids are engaged in complex interactions with the innate and adaptive immune systems, both of which may also play a role in the regulation of AD onset and progression.

Strategy for improving circular dichroism spectra deconvolution accuracy for macrocyclic peptides in drug discovery.

Peptide therapeutics have emerged as an appealing modality in the pharmaceutical industry. Understanding peptide conformation in solution remains one of the most critical areas for peptide drug development. Circular dichroism (CD) spectroscopy is a useful technique to study the secondary structure of proteins and peptides, but the current approaches are limited to protein-focused models to predict high-order structures of peptides, and the models were built based on X-ray crystallography instead of solution-based technique, as a result, such models may have poor predictions for peptides.

To 200,000 / and Beyond: Native Electron Capture Charge Reduction Mass Spectrometry Deconvolves Heterogeneous Signals in Large Biopharmaceutical Analytes.

Great progress has been made in the detection of large biomolecular analytes by native mass spectrometry; however, characterizing highly heterogeneous samples remains challenging due to the presence of many overlapping signals from complex ion distributions. Electron-capture charge reduction (ECCR), in which a protein cation captures free electrons without apparent dissociation, can separate overlapping signals by shifting the ions to lower charge states. The concomitant shift to higher / also facilitates the exploration of instrument upper / limits if large complexes are used.

A High Dynamic Range Ion Detector for Multireflection Time-of-Flight Analyzers.

Reflectron-based time-of-flight analyzers rely on subnanosecond detector time response to achieve acceptable resolving power for low-mid-mass, multiple-ion peaks. With the adoption of multireflection analyzers, order of magnitude longer folded ion paths relax restrictions on detector response time, allowing implementation of new technologies that greatly improve dynamic range, detector lifetime, and ion detection efficiency. A detection system is presented, integrated into a multireflection analyzer, that combines 10 keV postacceleration and focal plane correction with a unique BxE focusing, optically coupled detector, preamplification, and dual-channel digitization.

Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells.

Ovarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian cancer ascites obtained before and after chemotherapy and in vitro therapy-induced secretomes, we show that molecules secreted by ovarian cancer cells upon therapy promote cisplatin resistance and enhance DNA damage repair in recipient cancer cells. Even a short-term incubation of chemonaive ovarian cancer cells with therapy-induced secretomes induces changes resembling those that are observed in chemoresistant patient-derived tumor cells after long-term therapy.

Minimally invasive interventions for complications associated with intra-abdominal calculi after laparoscopic cholecystectomy.

Objective: To study the possibilities of minimally invasive methods for removing intra-abdominal calculi after laparoscopic cholecystectomy.

Material And Methods: There were 5 patients with abdominal abscesses associated with infected calculi after previous laparoscopic cholecystectomy at the Sklifosovsky Research Institute for Emergency Care between 2020 and 2023. Mean age of patients was 55±12 years.

A Hybrid Orbitrap-Nanoelectromechanical Systems Approach for the Analysis of Individual, Intact Proteins in Real Time.

Nanoelectromechanical systems (NEMS)-based mass spectrometry (MS) is an emerging technique that enables determination of the mass of individual adsorbed particles by driving nanomechanical devices at resonance and monitoring the real-time changes in their resonance frequencies induced by each single molecule adsorption event. We incorporate NEMS into an Orbitrap mass spectrometer and report our progress towards leveraging the single-molecule capabilities of the NEMS to enhance the dynamic range of conventional MS instrumentation and to offer new capabilities for performing deep proteomic analysis of clinically relevant samples. We use the hybrid instrument to deliver E.

Data Acquisition and Intraoperative Tissue Analysis on a Mobile, Battery-Operated, Orbitrap Mass Spectrometer.

Mass spectrometry has been increasingly explored in intraoperative studies as a potential technology to help guide surgical decision making. Yet, intraoperative experiments using high-performance mass spectrometry instrumentation present a unique set of operational challenges. For example, standard operating rooms are often not equipped with the electrical requirements to power a commercial mass spectrometer and are not designed to accommodate their permanent installation.

Oxidative Transformation of 2-Furylanilines into Indolin-3-ones.

Oxidation of 2-furylaninlies with -CPBA followed by treatment with a base provides access to functionalized indolin-3-ones. The designed oxidative transformation utilizes an underassessed chemical behavior of furyl-containing amines to form a C-N bond via engaging a β-carbon atom of the furan core upon a ring-forming step, thereby providing an alternative disconnection toward nitrogen-containing heterocycles.