Single-molecule systems for the detection and monitoring of plasma-circulating nucleosomes and oncoproteins in diffuse midline glioma.

The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG).

A graph neural network-based model with out-of-distribution robustness for enhancing antiretroviral therapy outcome prediction for HIV-1.

Predicting the outcome of antiretroviral therapies (ART) for HIV-1 is a pressing clinical challenge, especially when the ART includes drugs with limited effectiveness data. This scarcity of data can arise either due to the introduction of a new drug to the market or due to limited use in clinical settings, resulting in clinical dataset with highly unbalanced therapy representation. To tackle this issue, we introduce a novel joint fusion model, which combines features from a Fully Connected (FC) Neural Network and a Graph Neural Network (GNN) in a multi-modality fashion.

CD44 in myEloid cells is a major driver of liver inflammation and injury in alcohol-related liver disease.

Background And Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH). CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to ASH development in mice and its expression in ALD patients.

The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis.

Although chromatin remodelers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), the roles of these complexes during brain development are in many cases unclear. Here, we focused on the recently discovered ChAHP chromatin remodeling complex. The zinc finger and homeodomain transcription factor ADNP is a core subunit of this complex, and de novo mutations lead to intellectual disability and autism spectrum disorder.

Standard: Human gastric organoids.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.

Detection and quantification of ergothioneine in human serum using surface enhanced Raman scattering (SERS).

Ergothioneine (ERG) is a natural sulfur-containing amino acid found in many organisms, including humans. It accumulates at high concentrations in red blood cells and is distributed to various organs, including the brain. ERG has numerous health benefits and antioxidant capabilities, and it has been linked to various human physiological processes, such as anti-inflammatory, neuroprotective, and anti-aging effects.

Modeling the navigating forces behind BSA aggregation in a microfluidic chip.

Microfluidic chips are powerful tools for investigating numerous variables including chemical and physical parameters on protein aggregation. This study investigated the aggregation of bovine serum albumin (BSA) in two different systems: a vial-based static system and a microfluidic chip-based dynamic system in which BSA aggregation was induced successfully. BSA aggregation induced in a microfluidic chip on a timescale of seconds enabled a dynamic investigation of the forces driving the aggregation process.

Current Scenario in Associating Clinical COVID-19 Biomarkers for Developing Surveillance Platforms.

The novel coronavirus that caused the epidemic and pandemic resulting in the acute respiratory illness known as coronavirus disease 2019 (COVID-19) has plagued the world. This is unlike other coronavirus outbreaks that have occurred in the past, such as Middle East respiratory syndrome (MERS) or severe acute respiratory syndrome (SARS). COVID-19 has spread more quickly and posed special challenges due to the lack of appropriate treatments and vaccines.

TSC complex decrease the expression of mTOR by regulated miR-199b-3p.

The TSC complex formed by TSC1 and TSC2 is the most important upstream negative regulator of mTORC1. Genetic variations in either TSC1 or TSC2 cause tuberous sclerosis complex (TSC) disease which is a rare autosomal dominant disorder resulting in impairment of multiple organ systems. In this study, besides a reported variation, c.

Morphology remodelling and membrane channel formation in synthetic cells via reconfigurable DNA nanorafts.

The shape of biological matter is central to cell function at different length scales and determines how cellular components recognize, interact and respond to one another. However, their shapes are often transient and hard to reprogramme. Here we construct a synthetic cell model composed of signal-responsive DNA nanorafts, biogenic pores and giant unilamellar vesicles (GUVs).

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens.

Exploring similarities and differences in anti-atherosclerotic potential bioactives among Dendrobium species by UPLC-Q-Exactive Orbitrap MS.

Atherosclerosis is a primary cause of cardiovascular disease, straining healthcare systems. Dendrobium officinale, a widely used food-medicine homology, has demonstrated anti-atherosclerotic (anti-AS) properties, with other species listed in pharmacopoeias exhibiting similar effects. However, their efficacy varies, and the impact of interspecies variations on compounds and mechanisms in Dendrobium's anti-AS effects remains unclear.

A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis.

Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.

Distinguishing abiotic corrosion from two types of microbiologically influenced corrosion (MIC) using a new electrochemical biofilm/MIC test kit.

Biofilms can cause biofouling, water quality deterioration, and transmission of infectious diseases. They are also responsible for microbiologically influenced corrosion (MIC) which can cause leaks, resulting in environmental disasters. A new disposable biofilm/MIC test kit was demonstrated to distinguish abiotic corrosion of carbon steel from MIC.

Synthetic Lipid Biology.

Cells contain thousands of different lipids. Their rapid and redundant metabolism, dynamic movement, and many interactions with other biomolecules have justly earned lipids a reputation as a vexing class of molecules to understand. Further, as the cell's hydrophobic metabolites, lipids assemble into supramolecular structures─most commonly bilayers, or membranes─from which they carry out myriad biological functions.

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.