bioRxiv (Cold Spring Harbor Laboratory)

Data-independent acquisition (DIA) mass spectrometry has emerged as a powerful tool for neuropeptidomics, but its success relies heavily on the quality of spectral libraries used for peptide identification. There are inherent challenges to mass spectrometry analysis of crustacean neuropeptides, including the endogenous nature in which they are analyzed, extensive post-translational modification (…

The human genome is pervasively transcribed into protein-coding and regulatory non-coding RNAs whose functions are coordinated within higher-order nuclear architectures. However, direct mapping of RNA-RNA and DNA-DNA interaction networks in complex human tissues at single-cell resolution has remained a major challenge. Here, we present SCIENCE-seq, a multimodal single-cell interactomics platform …

The leukocyte-specific β2-integrin receptor family exerts a wide range of functions: β2- integrins are involved in leukocyte trafficking, where they mediate cell adhesion during inflammatory responses via binding to ICAM-1, ICAM-2, or JAM-C. Furthermore, they are essential for the recognition and phagocytosis of pathogens opsonized by complement. Accordingly, the β2-integrin family is known to be…

Targeted radiopharmaceutical development for ovarian cancer (OC) has been limited by the lack of molecular targets that combine broad tumor expression with minimal normal-tissue distribution. TRA-1-60 (TRA) is a cancer-associated glycoepitope carried by podocalyxin. Here, we evaluated TRA as a target for OC and developed a TRA-directed immunoPET imaging platform. Immunohistochemical analysis demo…

Circadian rhythms are driven by daily cellular clocks throughout the body that maintain optimal health. Glucocorticoid (GC) hormones are vital for synchronising cellular clocks, aligning them with external day/night cycles, but the mechanism was unresolved. We use a glucocorticoid receptor (GR) KO/rescue approach to show that residue E755 and the N-terminal intrinsically disordered region are ess…

Whole-genome duplication (WGD; or polyploidy) has played a major role in the evolution of many lineages however, our understanding of the processes that shape genome evolution following WGD remains incomplete. While polyploidy duplicates the entire genome sequence, it is rediploidisation that establishes inde- pendent duplicated genes. Rediploidisation proceeds through suppression of meiotic reco…

The urinary bladder functions to store and release urine, yet how the sensation of bladder fullness is conveyed and perceived to the central nervous system is not understood. During bladder filling, the detrusor smooth muscle (DSM) generates phasic contractions, resulting in pressure fluctuations within the bladder. These transient pressure events drive bursts of afferent nerve activity, yet the …

Fluorescent proteins are fundamental tools for cellular imaging. Most fluorescent proteins in routine use, including GFP, are derived from the jellyfish Aequorea victoria and emit blue-green light, which is strongly absorbed and scattered by tissue, limiting imaging depth. Far-red and near-infrared fluorescent proteins, engineered from bacteriophytochromes, address this limitation because far-red…

Purpose: High dietary fibre intake has been linked to lower cancer risk, yet its role in prostate cancer treatment responses and radiotherapy tolerance remains unclear. We evaluated the effects of dietary fibres (inulin, pectin, beta glucan) on prostate tumour growth, gut microbiota and intestinal response to ionising radiation (IR) in murine models. Methods: Male FVB and C57BL/6J mice were injec…

Osteosarcoma (OS) is the most common primary malignant bone tumour and is characterised by aggressive growth, early metastasis, and a very stagnant clinical outcome. Although epigenetic dysregulation has been implicated in OS progression, the mechanisms linking epigenetic alterations to metastatic signalling remain unclear. Here, we identified the lysine-protein demethylase 6A (KDM6A/UTX) as a cr…

Induced systemic resistance (ISR) is activated in leaves upon root colonization by beneficial microbes, yet the signals linking rhizosphere perception to shoot immunity remain unknown. In the Arabidopsis thaliana-Pseudomonas simiae WCS417 model interaction, the root-specific transcription factor MYB72 and its target gene BGLU42 regulate ISR and the production, activation, and root secretion of co…

Protein thiyl radicals are transient reactive intermediates in oxidative stress and enzymatic catalysis. However, their global profiling in living systems remains challenging due to the lack of suitable tools. Here, we report the first chemoproteomic probes enabling proteome-wide, residue-level identification of protein thiyl radicals in living cells. Designed to leverage sulfur-mediated stabiliz…

Introduction: Understanding mid-term test-retest reliability and within-subject variability is important for interpreting changes observed in longitudinal and intervention studies. The reliability of resting-state functional magnetic resonance imaging (rs-fMRI) is known to vary across measures and brain regions. However, how reliability differs across functional networks and connectivity- and amp…

Acetyl-CoA and other acyl-CoA thioesters are critical intermediates in the metabolic reactions that cells rely on to produce energy and carry out biosynthesis. Therefore, the analysis of acyl-CoA provides valuable information about the metabolic activity of cells, especially when combined with stable isotope tracing. Acyl-CoA species are routinely monitored by reversed-phase liquid chromatography…

Quantitative membrane proteomics remains fundamentally limited by sample preparation because detergent extraction can perturb membrane protein interactions, ligand-responsive conformations, and higher-order assemblies before mass spectrometric analysis. Here, we demonstrate that peptide-based surfactants (Peptergents) enable a complete detergent-free workflow for native membrane proteomics. Membr…

Deep learning tools are increasingly used today, particularly in medical segmentation. A gap nonetheless remains in automating segmentation for insects. This work addresses the following question: can a generalist segmentation model, trained on several phylogenetically related orthopteran species, reliably automate head tissue segmentation from micro-CT images? To answer this, we used nnU-Net, a …

The development of a new integrated operant system was driven by two challenges in behavioral neuroscience: the high cost and technical complexity of commercial rigs, and their limited adaptability across experiments. We developed the NeuroHab, an integrated behavioral arena for high-fidelity operant conditioning and automated data collection in a single unified system. Food and water reward, con…

Background: Although human milk (HM) confers important health benefits, how bioactive milk components (e.g., microbiota, oligosaccharides, and fatty acids) interact with infant genetics to influence childhood atopy remains poorly understood. Objective: We investigated interactions between infant genomic susceptibility and exposure to maternal human milk components (HMCs) and assessed whether inte…

Quantification of microbial growth inhibition is central to assays ranging from antibiotic susceptibility of bacteria to sensitivity of yeasts to antifungal therapeutics. Classical analysis approaches derive from zone-of-inhibition (termed halo) formats using filter paper discs, spanning methods from laser detection to machine learning. However, these tools struggle with non-uniform halos, fail t…

Background: The African green monkey (AGM) is increasingly used as a model for early stage Alzheimer's disease (AD), with cerebrospinal fluid (CSF) targeted for biomarker discovery and longitudinal disease monitoring of shifts in the central nervous system. MicroRNAs (miRNAs) are particularly informative indicators of early neuropathological change. Despite the complementary value of an early sta…