Co-expression of the RPS6KB1 and PDPK1 genes for production of activated p70S6K1 using bac-to-bac baculovirus expression system.

Background: Ribosomal protein S6 kinase 1 (p70S6K1) is a member of the AGC family of serine/threonine kinases which plays a role in various cellular processes, including protein synthesis, cell growth, and survival. Dysregulation of p70S6K1, characterized by its overexpression and/or hyperactivation, has been implicated in numerous human pathologies, particularly in several types of cancer. Therefore, generating active, recombinant p70S6K1 is critical for investigating its role in cancer biology and for developing novel diagnostic or therapeutic approaches.

The molecular features of non-peptidic nucleophilic substrates and acceptor proteins determine the efficiency of sortagging.

Sortase A-mediated ligation (SML) or "sortagging" has become a popular technology to selectively introduce structurally diverse protein modifications. Despite the great progress in the optimization of the reaction conditions and design of miscellaneous C- or N-terminal protein modification strategies, the reported yields of conjugates are highly variable. In this study, we have systematically investigated C-terminal protein sortagging efficiency using a combination of several rationally selected and modified acceptor proteins and a panel of incoming surrogate non-peptidic amine nucleophile substrates varying in the structural features of their amino linker parts and cargo molecules.

Cardiomyocyte engineering: The meeting point of transcription factors, signaling networks, metabolism and function.

Direct cardiac reprogramming or transdifferentiation is a relatively new and promising area in regenerative therapy, cardiovascular disease modeling, and drug discovery. Effective reprogramming of fibroblasts is limited by their plasticity, that is, their ability to reprogram, and depends on solving several levels of tasks: inducing cardiomyocyte-like cells and obtaining functionally and metabolically mature cardiomyocytes. Currently, in addition to the use of more classical approaches such as overexpression of exogenous transcription factors, activation of endogenous cardiac transcription factors via controlled nucleases, such as CRISPR, represents another interesting way to obtain cardiomyocytes.

Differences in association between hypoalbuminaemia and mortality among younger versus older patients on haemodialysis.

Background: Ageing often affects biomarker production. Yet, clinical/optimal thresholds to guide clinical decisions do not consider this. Serum albumin decreases with age, but hypoalbuminaemia is defined as serum albumin <4.

Discovery of highly active kynureninases for cancer immunotherapy through protein language model.

Tailor-made enzymes empower a wide range of versatile applications, although searching for the desirable enzymes often requires high throughput screening and thus poses significant challenges. In this study, we employed homology searches and protein language models to discover and prioritize enzymes by their kinetic parameters. We aimed to discover kynureninases as a potentially versatile therapeutic enzyme, which hydrolyses L-kynurenine, a potent immunosuppressive metabolite, to overcome the immunosuppressive tumor microenvironment in anticancer therapy.

Amperometric Biosensor Based on Glutamate Oxidase to Determine Ast Activity.

This work presents the development of an amperometric biosensor for detecting aspartate aminotransferase (AST) activity in biological fluids using a platinum disk electrode as the working transducer. Optimal concentrations of substrates (aspartate, α-ketoglutarate) and the coenzyme (pyridoxal phosphate) were determined to ensure efficient biosensor operation. A semi-permeable poly-m-phenylenediamine membrane was applied to enhance selectivity against electroactive interferents.

Pyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the HS/AKT/GSK3β signaling axis.

Pyridoxal-5-phosphate (PLP) enhances the synthesis of endogenous hydrogen sulfide, a potent regulator of cell metabolism. We used 24-month-old rats to investigate the PLP mitoprotective function in the aging heart. We demonstrated improvement of mitochondrial bioenergetic functions, inhibition of mPTP opening after PLP administration.

Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides.

Animal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with comprehensively constructing and expressing highly complex venom and venom-like molecule libraries have precluded their therapeutic evaluation via high throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and "metavenoms".

Fluid overload trajectories and mortality in hemodialysis patients.

Background: Fluid overload remains critical in managing patients with end-stage kidney disease. However, there is limited empirical understanding of fluid overload's impact on mortality. This study analyzes fluid overload trajectories and their association with mortality in hemodialysis patients.

IDENTIFICATION OF CLINICALLY RELEVANT GENE VARIANTS IN COLON ADENOCARCINOMA SAMPLES OF UKRAINIAN PATIENTS USING A COMPREHENSIVE CANCER PANEL: A PILOT STUDY.

Unlabelled: The study aimed to identify the clinically relevant gene variants in colon adenocarcinoma samples of Ukrainian patients using the NGS Comprehensive Cancer Panel (CCP) to implement them conveniently in clinical practice.

Methods: We have studied 20 samples of Ukrainian patients with colorectal adenocarcinomas of various differentiation grades. To identify the clinically relevant gene variants, the CCP data were filtered using the Franklin by Genoox database.

Development and optimisation of the biosensor for aspartate aminotransferase blood level determination.

This work presents the development and optimisation of an amperometric biosensor for determining aspartate aminotransferase (AST) activity in blood serum, using glutamate oxidase and platinum disc electrodes. AST is a key biomarker for diagnosing cardiovascular and liver diseases. The biosensor's bioselective membrane composition and formation protocol and the working solution (aspartate 8 mM, α-ketoglutarate 2 mM, pyridoxal-5-phosphate 100 µM) were optimised.

Longitudinal studies: focus on trajectory analysis in kidney diseases.

Longitudinal cohort studies are pivotal in medical research for understanding disease progression over time. These studies track a group of individuals across multiple time points, enabling the identification of risk factors and the evaluation of interventions. Traditional methods like linear mixed models, generalized estimating equations, and survival analysis often fall short in capturing the complex, non-linear patterns of disease progression.

The mechanisms underlying the cardiac effects of modified citrus pectin in obese rats with myocardial ischemia: Role of galectin-3.

Background: Modified citrus pectin (MCP) is used as a nutritional supplement that inhibits galectin-3 activity, a central player in the cardiac damage associated with different pathological situations. In fact, we have previously observed that MCP improved cardiac function in obese infarcted rats that was associated with a reduction in cardiac fibrosis. Therefore, the aim of the present study was to further explore whether this effect could involve the modulation of gene expression of ECM components and their mediators as well as whether it could affect another two mechanisms involved in cardiac damage: mitochondrial dynamics and autophagic flux.

Structural Insight on the Selectivity of Calyx[4]Arene-Based Inhibitors of MgDependent Atp-Hydrolases.

Located in plasma membranes, ATP hydrolases are involved in several dynamic transport processes, helping to control the movement of ions across cell membranes. ATP hydrolase acts as a transport protein, converting energy from ATP hydrolysis into transport molecules against their concentration gradients. In addition to energy metabolism and active transport, ATP hydrolase is essential for maintaining cellular homeostasis and cell function.

Bilingual language model for protein sequence and structure.

Adapting language models to protein sequences spawned the development of powerful protein language models (pLMs). Concurrently, AlphaFold2 broke through in protein structure prediction. Now we can systematically and comprehensively explore the dual nature of proteins that act and exist as three-dimensional (3D) machines and evolve as linear strings of one-dimensional (1D) sequences.

Unraveling membrane protein localization and interactions in nanodiscs.

Nanodiscs, consisting of a lipid bilayer surrounded by membrane scaffold proteins (MSPs), are extensively used to study membrane proteins (MPs) because they provide a stable lipid environment. However, the precise mechanism governing MP behavior within the nanodisc remains elusive. Here, we examined the cryo-EM structures of various MPs reconstituted in nanodiscs from EMPIAR.

Exploring the metaverse: opportunities for nephrology in patient care and education.

The metaverse, a digital ecosystem characterized by the convergence of physical and virtual realities through technologies like virtual reality (VR), augmented reality (AR), and mixed reality (MR), is reshaping societal and economic landscapes. In healthcare, the metaverse promises to revolutionize service delivery and medical education by overcoming geographical barriers and democratizing access to information. However, challenges such as the digital divide and privacy concerns persist.

REST-dependent glioma progression occurs independently of the repression of the long non-coding RNA HAR1A.

The long non-coding RNA (lncRNA), HAR1A is emerging as a putative tumour suppressor. In non-neoplastic brain cells, REST suppresses HAR1A expression. In gliomas REST acts as an oncogene and is a potential therapeutic target.

Clinical trial emulation in nephrology.

Trial emulation, also known as target trial emulation, has significantly advanced epidemiology and causal inference by providing a robust framework for deriving causal relationships from observational data. This approach aims to reduce biases and confounding factors inherent in observational studies, thereby improving the validity of causal inferences. By designing observational studies to mimic randomized controlled trials (RCTs) as closely as possible, researchers can better control for confounding and bias.

BFVD-a large repository of predicted viral protein structures.

The AlphaFold Protein Structure Database (AFDB) is the largest repository of accurately predicted structures with taxonomic labels. Despite providing predictions for over 214 million UniProt entries, the AFDB does not cover viral sequences, severely limiting their study. To address this, we created the Big Fantastic Virus Database (BFVD), a repository of 351 242 protein structures predicted by applying ColabFold to the viral sequence representatives of the UniRef30 clusters.

Glia-like taste cells mediate an intercellular mode of peripheral sweet adaptation.

The sense of taste generally shows diminishing sensitivity to prolonged sweet stimuli, referred to as sweet adaptation. Yet, its mechanistic landscape remains incomplete. Here, we report that glia-like type I cells provide a distinct mode of sweet adaptation via intercellular crosstalk with chemosensory type II cells.