Stratified Medicine Paediatrics: Cell free DNA and serial tumour sequencing identifies subtype specific cancer evolution and epigenetic states.

We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and paired plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tissue and cfDNA sequencing results were concordant, with a wider spectrum of mutant alleles and higher degree of intra-tumour heterogeneity captured by the latter, if sufficient circulating tumour-derived DNA (ctDNA) was present. Serial tumour sequencing identified putative drivers of relapse, with alterations in epigenetic drivers being a common feature.

Dextromethorphan inhibits collagen and collagen-like cargo secretion to ameliorate lung fibrosis.

Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis.

GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease-like filaments.

The pathological deposition of proteins is a hallmark of several devastating neurodegenerative diseases. These pathological deposits comprise aggregates of proteins that adopt distinct structures named strains. However, the molecular factors responsible for the formation of distinct aggregate strains are unknown.

Proteomic analysis of the sponge Aggregation Factor implicates an ancient toolkit for allorecognition and adhesion in animals.

The discovery that sponges (Porifera) can fully regenerate from aggregates of dissociated cells launched them as one of the earliest experimental models to study the evolution of cell adhesion and allorecognition in animals. This process depends on an extracellular glycoprotein complex called the Aggregation Factor (AF), which is composed of proteins thought to be unique to sponges. We used quantitative proteomics to identify additional AF components and interacting proteins in the classical model, , and compared them to proteins involved in cell interactions in Bilateria.

An antibiotic that mediates immune destruction of senescent cancer cells.

Drugs that eliminate senescent cells, senolytics, can be powerful when combined with prosenescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation, and interferes with redox signaling, leading to death of senescent cells.

Genetic Signatures of Contrasted Outbreak Histories of " Liberibacter asiaticus", the Bacterium That Causes Citrus Huanglongbing, in Three Outermost Regions of the European Union.

In an era of trade globalization and climate change, crop pathogens and pests are a genuine threat to food security. The detailed characterization of emerging pathogen populations is a prerequisite for managing invasive species pathways and designing sustainable disease control strategies. Huanglongbing is the disease that causes the most damage to citrus, a crop that ranks #1 worldwide in terms of fruit production.

Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Surveillance Outcome Program (ASSOP) Bloodstream Infection Annual Report 2023.

From 1 January to 31 December 2023, fifty-seven institutions across Australia participated in the Australian Surveillance Outcome Program (ASSOP). The aim of ASSOP 2023 was to determine the proportion of bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on methicillin resistance, and to characterise the methicillin-resistant (MRSA) molecular epidemiology. A total of 3,422 SAB episodes were reported, of which 77.

Australian Group on Antimicrobial Resistance (AGAR) Australian Enterococcal Surveillance Outcome Program (AESOP) Bloodstream Infection Annual Report 2023.

From 1 January to 31 December 2023, fifty-six institutions across Australia participated in the Australian Enterococcal Surveillance Outcome Program (AESOP). The aim of AESOP 2023 was to determine the proportion of enterococcal bacteraemia isolates in Australia that were antimicrobial resistant, and to determine the molecular epidemiology. Of the 1,599 unique episodes of enterococcal bacteraemia investigated, 92.

The physiological and molecular responses of potato tuberization to projected future elevated temperatures.

Potato (Solanum tuberosum L.) is one of the most important food crops globally and is especially vulnerable to heat stress. However, substantial knowledge gaps remain in our understanding of the developmental mechanisms associated with tuber responses to heat stress.

Beyond-local neural information processing in neuronal networks.

While there is much knowledge about local neuronal circuitry, considerably less is known about how neuronal input is integrated and combined across neuronal networks to encode higher order brain functions. One challenge lies in the large number of complex neural interactions. Neural networks use oscillating activity for information exchange between distributed nodes.

Quantifying conformational changes in the TCR:pMHC-I binding interface.

Background: T cells form one of the key pillars of adaptive immunity. Using their surface bound T cell antigen receptors (TCRs), these cells screen millions of antigens presented by major histocompatibility complex (MHC) or MHC-like molecules. In other protein families, the dynamics of protein-protein interactions have important implications for protein function.

Exploring aliphatic sulfonamides as multiclass inhibitors of the carbonic anhydrases from the pathogen bacterium Vibrio cholerae.

This study investigates aliphatic sulfonamide derivatives as inhibitors of the α-, β-, and γ-class carbonic anhydrase (CA) isoforms from Vibrio cholerae (VchCAs). A series of 26 compounds bearing a triazole linker and urea- or ether-based tails were described and evaluated for their inhibitory action using a stopped-flow CO hydrase technique. These inhibitors demonstrated a preferential efficacy against VchCAβ.

Characterising a Novel Therapeutic Target for Psoriasis, TYK2, Using Functional Genomics.

Psoriasis (Ps) is a debilitating immune-mediated chronic skin condition. It affects about 1-3% of the world population, with an 8-11% prevalence in Northern European populations. Tyrosine kinase 2 (TYK2) is a newly identified target for Ps.

The Detection of Toxic Amyloid-β Fibril Fragments Through a Surface Plasmon Resonance Immunoassay.

Amyloid-β1-42 (Aβ42) forms highly stable and insoluble fibrillar structures, representing the principal components of the amyloid plaques present in the brain of Alzheimer's disease (AD) patients. The involvement of Aβ42 in AD-associated neurodegeneration has also been demonstrated, in particular for smaller and soluble aggregates (oligomers). Based on these findings and on genetic evidence, Aβ42 aggregates are considered key players in the pathogenesis of AD and targets for novel therapies.

Association of Inflammasome Gene Expression Levels with Pathogenesis of Familial Mediterranean Fever in Armenians.

Familial Mediterranean fever (FMF) is a genetically determined autoinflammatory disease transmitted mostly by an autosomal recessive mechanism and caused by point mutations of the (Mediterranean FeVer) gene. The aim of this study was to evaluate the expression of inflammasome genes (, , , and ) in patients with FMF compared to controls to understand the changes playing a key role in disease development. We found altered expression levels of the full-length isoform as well as and in FMF patients versus controls.

Functional Modulation of Gut Microbiota and Blood Parameters in Diabetic Rats Following Dietary Intervention with Free or Immobilized SK Cells on Pistachio Nuts.

Background/objectives: The gut microbiota is linked to the pathogenesis of type 1 diabetes mellitus (T1DM), while supplementation with probiotics may result in positive alterations in the composition of the gut microbiome. This research aimed to map the changes in the gut microbiome and blood markers of streptozotocin-induced diabetic rats after a dietary intervention with free or immobilized cells of the presumptive probiotic SK on pistachio nuts.

Methods: Twenty-four male Wistar rats were studied and divided into four groups (healthy or diabetic) which received the free or the immobilized .

Prediagnostic Plasma Nutrimetabolomics and Prostate Cancer Risk: A Nested Case-Control Analysis Within the EPIC Study.

: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. : We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Run-off impacts on Arctic kelp holobionts have strong implications on ecosystem functioning and bioeconomy.

Kelps (Laminariales, Phaeophyceae) are foundation species along Arctic rocky shores, providing the basis for complex ecosystems and supporting a high secondary production. Due to ongoing climate change glacial and terrestrial run-off are currently accelerating, drastically changing physical and chemical water column parameters, e.g.

Structural and biophysical characterization of the cytoplasmic domains of HprS kinase and its interactions with the cognate regulator HprR.

The HprSR constitutes the bacterial two-component regulatory system engaged by Escherichia coli to reduce the damaging effects of reactive chlorine and oxygen species present in its cytosol. Hypochlorous acid (HOCl) has been shown to be the molecule capable of activating of the HprSR system. HOCl is produced upon pathogen invasion by phagocytic cells of the human innate immune system, particularly neutrophils, to take advantage of its powerful antimicrobial attributes.

A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%).

Painting lysosomes to study organelle heterogeneity.

Like other organelles, the heterogeneity of lysosomes within a single cell has been challenging to capture and study in detail. In this issue, Chen and Gutierrez discuss new work that tackles this question using DNA-PAINT imaging, from Lakadamyali and colleagues (https://doi.org/10.

Cyclic Olefin Copolymer-Based Fixed-Target Sample Delivery Device for Protein X-ray Crystallography.

Serial macromolecular X-ray crystallography plays an important role in elucidating protein structures and consequently progressing the field of targeted therapeutics. The use of pulsed beams at different repetition frequencies requires the development of various sample-conserving injection strategies to minimize sample wastage between X-ray exposures. Fixed-target sample delivery methods that use solid support to hold the crystals in the X-ray beam path are gaining interest as a sample-conserving delivery system for X-ray crystallography with high crystal hit rates.

Mesoscopic axially swept oblique plane microscope for the imaging of freely moving organisms with near-isotropic resolution.

Rapid three-dimensional imaging over extended fields of view (FOVs) is crucial to the study of organism-wide systems and biological processes . Selective-plane illumination microscopy (SPIM) is a powerful method for high spatio-temporal resolution imaging of such biological specimens. However, typical SPIM implementations preclude conventional sample mounting and have anisotropic imaging performance, in particular when designed for large FOVs over 1 mm diameter.

Geographical factors and air raid alarms influence leptospirosis epidemiology in Ukraine (2018-2023).

Leptospirosis, a widespread zoonotic disease caused by spp., affects approximately 1 million people annually and causes about 58,000 deaths worldwide. This study examines the epidemiology of leptospirosis in Ukraine from 2018 to 2023, focusing on the impact of weather and geographical factors on disease transmission.