Involvement of GTPases and vesicle adapter proteins in Heparan sulfate biosynthesis: role of Rab1A, Rab2A and GOLPH3.

Vesicle trafficking is pivotal in heparan sulfate (HS) biosynthesis, influencing its spatial and temporal regulation within distinct Golgi compartments. This regulation modulates the sulfation pattern of HS, which is crucial for governing various biological processes. Here, we investigate the effects of silencing Rab1A and Rab2A expression on the localisation of 3-O-sulfotransferase-5 (3OST5) within Golgi compartments and subsequent alterations in HS structure and levels.

Key Interaction Changes Determine the Activation Process of Human Parathyroid Hormone Type 1 Receptor.

The parathyroid hormone type 1 receptor (PTH1R) plays a crucial role in modulating various physiological functions and is considered an effective therapeutic target for osteoporosis. However, a lack of detailed molecular and energetic information about PTH1R limits our comprehensive understanding of its activation process. In this study, we performed computational simulations to explore key events in the activation process, such as conformational changes in PTH1R, Gs protein coupling, and the release of guanosine diphosphate (GDP).

Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity.

Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity.

Drug Property Optimization: Design, Synthesis, and Characterization of Novel Pharmaceutical Salts and Cocrystal-Salt of Lumefantrine.

Lumefantrine (LMF) is a low-solubility antimalarial drug that cures acute, uncomplicated malaria. It exerts its pharmacological effects against erythrocytic stages of spp. and prevents malaria pathogens from producing nucleic acid and protein, thereby eliminating the parasites.

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.

Aims: The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health.

Structurally programmable, functionally tuneable dendrimers in biomedical applications.

The application of nanotechnology in medical biology has seen a significant rise in recent years because of the introduction of novel tools that include supramolecular systems, complexes, and composites. Dendrimers are one of the remarkable examples of such tools. These spherical, regularly branching structures with enhanced cell compatibility and bioavailability have shown to be an excellent option for gene or drug administration.

Simultaneous Profiling of Multiple Phosphorylated Metabolites in Typical Biological Matrices via Ion-Pair Reversed-Phase Ultrahigh-Performance Liquid Chromatography and Mass Spectrometry.

Simultaneous analysis of multiple phosphorylated metabolites (phosphorylated metabolome) in biological samples is vital to reveal their physiological and pathophysiological functions, which is extremely challenging due to their low abundance in some biological matrices, high hydrophilicity, and poor chromatographic behavior. Here, we developed a new method with ion-pair reversed-phase ultrahigh-performance liquid chromatography and mass spectrometry using BEH C18 columns modified with hybrid surface technology. This method demonstrated good performances for various phosphorylated metabolites, including phosphorylated sugars and amino acids, nucleotides, NAD-based cofactors, and acyl-CoAs in a single run using standard LC systems.

A widespread family of viral sponge proteins reveals specific inhibition of nucleotide signals in anti-phage defense.

Cyclic oligonucleotide-based antiviral signaling systems (CBASS) are bacterial anti-phage defense operons that use nucleotide signals to control immune activation. Here we biochemically screen 57 diverse and phages for the ability to disrupt CBASS immunity and discover anti-CBASS 4 (Acb4) from the phage SPO1 as the founding member of a large family of >1,300 immune evasion proteins. A 2.

Organ injury accelerates stem cell differentiation by modulating a fate-transducing lateral inhibition circuit.

Injured epithelial organs must rapidly replace damaged cells to restore barrier integrity and physiological function. In response, injury-born stem cell progeny differentiate faster compared to healthy-born counterparts, yet the mechanisms that pace differentiation are unclear. Using the adult Drosophila intestine, we find that injury speeds cell differentiation by altering the lateral inhibition circuit that transduces a fate-determining Notch signal.

Novel Natural Candidates for Replacing Synthetic Additives in Nutraceutical and Pharmaceutical Areas: Two Species ( (L.) Roxb. and (L.) Link).

(L.) Roxb. and (L.

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.

Polystyrene nanoparticles induce DNA damage and apoptosis in HeLa cells.

Nanoplastics (NPs) are plastic particles, typically less than 100 nm in size, that result from daily life products as well as the degradation of larger plastic debris. Due to their small size and chemical composition, they can interact with biological systems in ways that larger plastic particles cannot. Humans are continuously exposed to NPs and several studies showed the potentially toxic effects of these latter on health.

Enhancing chemical signal transformation in lateral flow assays using aptamer-architectured plasmonic nanozymes and para-phenylenediamine.

The widespread adoption and commercialization of lateral flow assays (LFAs) for clinical diagnosis have been hindered by limitations in sensitivity, specificity, and the absence of quantitative data. To address these challenges, we developed aptamer-architectured gold nanoparticles as nanozymes that catalytically convert -phenylenediamine (PPD) into Bandrowski's base (BB), thereby amplifying signal strength and sensitivity. The physiochemical properties of the nanozymes were characterized and their specific binding efficiency was demonstrated using experimental studies.

Drug carrier-assisted combined chemo- and radionuclide therapy for tumors of diverse origins: effects of therapeutic schemes on tumor responses.

Despite the promising results in cancer treatment, standard monotherapy remains insufficient for a wide range of oncological diseases. Combined therapy can significantly improve therapeutic outcomes compared to single-agent treatments. However, identifying the optimal treatment regimen for combined therapy can be a challenging task.

Structure-Activity Relationship of Ciprofloxacin towards S-Spike Protein of SARS-CoV-2: Synthesis and Evaluation.

The recent outbreak of the coronavirus (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has posed serious threats to global health systems. Although several directions have been put by the WHO for effective treatment, use of antibiotics, particularly ciprofloxacin, in suspected and acquired Covid-19 patients has raised an even more serious concern of antibiotic resistance. Ciprofloxacin has been reported to inhibit entry of SARS-CoV-2 into the host cells via interacting with the spike (S) protein.

A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5.

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.

Adaptive evolution of stress response genes in parasites aligns with host niche diversity.

Background: Stress responses are key the survival of parasites and, consequently, also the evolutionary success of these organisms. Despite this importance, our understanding of the evolution of molecular pathways dealing with environmental stressors in parasitic animals remains limited. Here, we tested the link between adaptive evolution of parasite stress response genes and their ecological diversity and species richness.

A multilevel social network approach to studying multiple disease-prevention behaviors.

The effective prevention of many infectious and non-infectious diseases relies on people concurrently adopting multiple prevention behaviors. Individual characteristics, opinion leaders, and social networks have been found to explain why people take up specific prevention behaviors. However, it remains challenging to understand how these factors shape multiple interdependent behaviors.

CRISPR-Hybrid: A CRISPR-Mediated Intracellular Directed Evolution Platform for RNA Aptamers.

Recent advances in gene editing and precise regulation of gene expression based on CRISPR technologies have provided powerful tools for the understanding and manipulation of gene functions. Fusing RNA aptamers to the sgRNA of CRISPR can recruit cognate RNA-binding protein (RBP) effectors to target genomic sites, and the expression of sgRNA containing different RNA aptamers permit simultaneous multiplexed and multifunctional gene regulations. Here, we report an intracellular directed evolution platform for RNA aptamers against intracellularly expressed RBPs.

Emerging models to study competitive interactions within bacterial communities.

Within both abiotic and host environments, bacteria typically exist as diverse, multispecies communities and have crucial roles in human health, agriculture, and industry. In these communities, bacteria compete for resources, and these competitive interactions can shape the overall population structure and community function. Studying bacterial community dynamics requires experimental model systems that capture the different interaction networks between bacteria and their surroundings.

Establishing In-vivo brain microdialysis for comparing concentrations of a variety of cortical neurotransmitters in the awake rhesus macaque between different cognitive states.

Background: Neuronal activity is modulated by behavior and cognitive processes. The combination of several neurotransmitter systems, acting directly or indirectly on specific populations of neurons, underlie such modulations. Most studies with non-human primates (NHPs) fail to capture this complexity, partly due to the lack of adequate methods for reliably and simultaneously measuring a broad spectrum of neurotransmitters while the animal engages in behavioral tasks.

Towards measurements of absolute membrane potential in Bacillus subtilis using fluorescence lifetime.

Membrane potential (MP) changes can provide a simple readout of bacterial functional and metabolic state or stress levels. While several optical methods exist for measuring fast changes in MP in excitable cells, there is a dearth of such methods for absolute and precise measurements of steady-state membrane potentials (MPs) in bacterial cells. Conventional electrode-based methods for the measurement of MP are not suitable for calibrating optical methods in small bacterial cells.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain.

The brain uses a specialized system to transport cerebrospinal fluid (CSF), consisting of interconnected ventricles lined by motile ciliated ependymal cells. These cells act jointly with CSF secretion and cardiac pressure gradients to regulate CSF dynamics. To date, the link between cilia-mediated CSF flow and brain function is poorly understood.