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Mashup Score: 1A metabolic-dysfunction associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system - 12 hour(s) ago
Preclinical and clinical studies suggest that lipid-induced hepatic insulin resistance is a primary defect that predisposes to dysfunction in pancreatic islets, implicating a perturbed liver-pancreas axis underlying the comorbidity of T2DM and MASLD. To investigate this hypothesis, we developed a human biomimetic microphysiological system (MPS) coupling our vascularized liver acinus MPS (vLAMPS) with primary islets on a chip (PANIS) enabling MASLD progression and islet dysfunction to be quantitatively assessed. The modular design of this system (vLAMPS-PANIS) allows intra-organ and inter-organ dysregulation to be deconvoluted. When compared to normal fasting (NF), under early metabolic syndrome (EMS) conditions, the standalone vLAMPS exhibited characteristics of early stage MASLD, while no significant differences were observed in the standalone PANIS. In contrast, with EMS, the coupled vLAMPS-PANIS exhibited a perturbed islet-specific secretome and a significantly dysregulated glucose
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Mashup Score: 1Perfusion-Independent Tissue Hypoxia in Cardiac Hypertrophy in Mice Measured by 64Cu-CTS PET Imaging - 12 hour(s) ago
Background: Hypoxia is central to many cardiac pathologies, but clinically its presence can only be inferred by indirect biomarkers including hypoperfusion and energetic compromise. Imaging hypoxia directly could offer new opportunities for the diagnosis and sub-stratification of cardiovascular diseases. Objectives: To determine whether [64Cu]CuCTS Positron Emission Tomography (PET) can identify hypoxia in a murine model of cardiac hypertrophy. Methods: Male C57BL/6 mice underwent abdominal aortic constriction (AAC) to induce cardiac hypertrophy, quantified by echocardiography over 4 weeks. Hypoxia and perfusion were quantified in vivo using [64Cu]CuCTS and [64Cu]CuGTSM PET, respectively, and radiotracer biodistribution was quantified post-mortem. Cardiac radiotracer retention was correlated with contractile function (measured by echocardiography), cardiac hypertrophy (measured by histology), HIF-1a; stabilization and NMR-based metabolomics. The effect of anesthesia on [64Cu]CuCTS upta
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Mashup Score: 2Detecting color differences in lentil flour samples using an inexpensive, hand-held colorimeter. - 12 hour(s) ago
Premise: The Nix Spectro 2 was developed to obtain CIEL*a*b* values from small samples and is an affordable alternative to the more expensive spectrophotometers typically used to assess food color. Methods: To validate the use of the Nix for lentil seed quality research, eight genotypes in three different field trials, were evaluated for flour color using HunterLab (illuminant C) and Nix (illuminants D50 and C) instruments and results compared for consistency. Results: The a* and b* Nix scores were comparable to those obtained with the HunterLab (r2 = 0.9-0.95). L* scores had lower correlation values: 0.61 and 0.58 when comparing HunterLab (C) with Nix (D50) and Nix (C), respectively. Discussion: Lower L* correlations could be a result of the influence of direct light exposure during HunterLab scans. In contrast, the Nix uses more technical repetitions per scan and avoids direct light exposure with the use of an adaptor, suggesting the L* Nix values are more reliable than those from
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Mashup Score: 2De Novo Genome assembly of the Caucasian dwarf goby Knipowitschia cf. caucasica, a new alien Gobiidae invading the River Rhine - 13 hour(s) ago
The Caucasian dwarf goby Knipowitschia cf. caucasica is a new invasive alien Gobiidae spreading in the Lower Rhine since 2019. Little is known about the invasion biology of the species and further investigations to reconstruct the invasion history are lacking genomic resources. We assembled a high-quality chromosome-scale reference genome of Knipowitschia cf. caucasica by combining PacBio, Omni-C and Illumina technologies. The size of the assembled genome is 956.58 Mb with a N50 scaffold length of 43 Mb, which includes 92.3 % complete vertebrate/Actinopterygii Benchmarking Universal Single-Copy Orthologs. 98.96 % of the assembly sequence was assigned to 23 chromosome-level scaffolds, with a GC-content of 42.83 %. Repetitive elements account for 53.08 % of the genome. The chromosome-level genome contained 49,622 transcripts with 42,926 multi-exons, of which 45,512 genes were functionally annotated. In summary, the high-quality genome assembly provides a fundamental basis to understand t
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Mashup Score: 2PACS-1 variant protein is aberrantly localized in C. elegans model of PACS1/PACS2 syndromes - 13 hour(s) ago
PACS (Phosphofurin Acidic Cluster Sorting Protein) proteins are known for their roles in sorting cargo proteins to organelles and can physically interact with WD40 repeat-containing protein WDR37. PACS1, PACS2, and WDR37 variants are associated with multisystemic syndromes and neurodevelopmental disorders characterized by intellectual disability, seizures, developmental delays, craniofacial abnormalities, and autism spectrum disorder. However, the effects of syndromic variants on function in vivo remains unknown. Here, we report the expression pattern of C. elegans orthologs of PACS and WDR37 and their interaction. We show that cePACS-1 and ceWDR-37 co-localize to somatic cytoplasm of many types of cells, and are mutually required for expression, supporting a conclusion that the intermolecular dependence of PACS1/PACS2/PACS-1 and WDR37/WDR-37 is evolutionarily conserved. We further show that editing in PACS1 and PACS2 variants in cePACS-1 changes protein localization in multiple cell t
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Mashup Score: 3
Honeybees (Apis mellifera) are a keystone species for managed pollination and the production of hive products. Eusociality in honeybees leads to much of the reproduction in a hive driven by the queen. Queen bees have two large active ovaries that can produce large numbers of eggs if conditions are appropriate. These ovaries are also active throughout the long lives of these insects, up to 5 years in some cases. Recent studies have indicated that the germline precursors of the adult honeybee queen ovary are organized into 8 cell clusters, joined together by a polyfusome; a cytoplasmic bridge. To understand the origin of these clusters, and trace the development of the honeybee queen ovary, we examined the cell types and regionalization of the developing larval and pupal queen ovaries. We used established (nanos and castor), and novel (odd skipped) gene expression markers to determine regions of the developing ovary. Primordial germline cells develop in the honeybee embryo and are organi
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Mashup Score: 2
scRNA-seq analysis relies heavily on single-cell clustering to perform many downstream functions. Several machine learning methods have been proposed to improve the clustering of single cells, yet most of these methods are fully unsupervised and ignore the wealth of publicly available annotated datasets from single-cell experiments. Cells are high-dimensional entities, and unsupervised clustering might find clusters without biological meaning. Exploiting relevant annotated scRNA-seq dataset as the learning reference can provide an algorithm with the knowledge that guides it to better estimate the number of clusters and find meaningful clusters in the target dataset. Results: In this paper, we propose Single Cell MUlti-Source CLustering, scMUSCL, a novel transfer learning method for finding clusters of cells in a target dataset by transferring knowledge from multiple annotated source (reference) datasets. scMUSCL relies on a deep neural network to extract domain and batch invariant cell
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Mashup Score: 1Neto proteins differentially modulate the gating properties of Drosophila NMJ glutamate receptors - 13 hour(s) ago
The formation of functional synapses requires co-assembly of ion channels with their accessory proteins which controls where, when, and how neurotransmitter receptors function. The auxiliary protein Neto modulates the function of kainate-type glutamate receptors in vertebrates as well as at the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse widely used for genetic studies on synapse development. We previously reported that Neto is essential for the synaptic recruitment and function of glutamate receptors. Here, using outside-out patch-clamp recordings and fast ligand application, we examine for the first time the biophysical properties of recombinant Drosophila NMJ receptors expressed in HEK293T cells and compare them with native receptor complexes of genetically controlled composition. The two Neto isoforms, Neto-α and Neto-β, differentially modulate the gating properties of NMJ receptors. Surprisingly, we found that deactivation is extremely fast and that the decay
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Mashup Score: 1Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species - 13 hour(s) ago
The lateral septum (LS) is a midline, subcortical structure, which regulates social behaviors that are frequently impaired in neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Mouse studies have identified neuronal populations within the LS that express a variety of molecular markers, including vasopressin receptor, oxytocin receptor, and corticotropin releasing hormone receptor, that control specific facets of social behavior. Despite its critical role in the regulation of social behavior and notable gene expression patterns, comprehensive molecular profiling of the human LS has not been performed. Here, we conducted single nucleus RNA-sequencing (snRNA-seq) to generate the first transcriptomic profiles of the human LS using postmortem human brain tissue samples from 3 neurotypical donors. Our analysis identified 4 transcriptionally distinct neuronal cell types within the human LS that are enriched for TRPC4, the gene encoding Trp-related protein 4. Di
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Mashup Score: 3Tumor suppressor p73 transcriptionally regulates c-FLIP to impede its priming of extrinsic apoptosis while a switcher compound degrades c-FLIP protein - 14 hour(s) ago
The tumor suppressor p73 is a member of the p53 family, and transcriptionally activates multiple p53-targets involved in cell cycle regulation and apoptosis. In addition to pro-apoptotic signaling, outcomes of p73 activation include cell survival signals. Thus, p73 activity and targets may provide insight in cell fate outcomes between cell survival and apoptosis following cellular stress. We report that cellular FLICE inhibitory protein (c-FLIP), a master antiapoptotic factor, is a transcriptional target of p73. The activation of p73 (alpha and beta isoforms) transcriptionally upregulates c-FLIP-L/S expression in cancer cells. The cell fate decision following p73 activation is determined by the adjustment of the balance of outcomes of p73 activation between p73-induced pro-apoptotic signaling and c-FLIP-L/S expression in cancer cells. p73 primes extrinsic apoptosis via an autocrine death ligand-DR5 axis, and the priming appears to be titrated at the level of c-FLIP-L/S. The p73-upregul
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A metabolic-dysfunction associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system https://t.co/SfCFSqtakn #bioRxiv