Search Results (111)

The nuclear RNA exosome, a conserved 3′→5′ ribonuclease complex, degrades the vast majority of RNA polymerase II output, including promoter upstream transcripts, enhancer RNAs, antisense transcripts, and retrotransposon-derived RNAs. Beyond this housekeeping role, the exosome acts as an epigenetic effector, and its dysfunction underlies a growing spectrum of human disease. Here we integrate recent structural, genomic, and disease-focused studies into a unified model of the exosome as a guardian of the epigenome. We describe how MTR4-containing adaptor complexes TRAMP, NEXT, and PAXT confer substrate selectivity, and how the exosome enforces heterochromatic silencing in concert with HP1 proteins and the Human Silencing Hub (HUSH) complex and preserves three-dimensional genome architecture at insulators and enhancers, such as the protocadherin locus where RNA surveillance, CTCF insulation, and heterochromatin converge. We then examine the consequences of failure: exosomopathies such as pontocerebellar hypoplasia, loss of DIS3- and PAXT-mediated tumor suppression in cancer, and age-related erosion of surveillance that permits transposable element de-repression, RIG-1/MDA5 and cGAS-STING-driven inflammation, cellular senescence, and neurodegeneration. We conclude that the exosome couples RNA decay to epigenetic state across the lifespan, positioning RNA surveillance as an emerging therapeutic target. Full article

To identify candidate genes associated with skin tissue responses in Hu sheep raised under different regional rearing environments and to preliminarily explore their potential relevance to low-temperature-related environmental responses, this study used 1-year-old female Hu sheep raised in Anhui and Xinjiang as the experimental animals. Skin tissues were collected from the left scapular region, and their transcriptomic profiles were characterized by integrating histological analysis, RNA sequencing (RNA-seq), differential expression analysis, functional enrichment analysis, protein–protein interaction (PPI) network construction, and RT-qPCR validation. The results showed significant differences between the two groups in body weight, body length, body height, cannon circumference, rectal temperature, and ear temperature. Hematoxylin and eosin (H&E) staining indicated that the Xinjiang group exhibited a denser distribution of hair follicles, a relatively thicker dermis, and a more compact arrangement of collagen fibers, suggesting enhanced insulation-related skin characteristics. Transcriptome sequencing identified 295 differentially expressed genes (DEGs), including 193 upregulated and 102 downregulated genes. GO and KEGG enrichment analyses showed that these DEGs were mainly involved in immune and inflammatory responses, redox processes, extracellular matrix remodeling, and lipid and energy metabolism-related pathways, with significant enrichment in cytokine–cytokine receptor interaction, the chemokine signaling pathway, the NF-κB signaling pathway, glutathione metabolism, and drug metabolism–cytochrome P450. By further integrating PPI network analysis and functional annotation, CXCL13, CCL2, FGF21, GPX3, CYP1A1, HSD11B1, CDO1, and STEAP4 were identified as candidate genes. RT-qPCR results showed that the expression trends of the selected genes were generally consistent with the RNA-seq results. Overall, this study revealed differences in phenotypic traits, skin histological structure, and transcriptomic characteristics between Hu sheep raised in different regions, providing preliminary molecular clues potentially associated with low-temperature-related environmental responses. Given the differences in geographic origin and rearing environments between the two groups, the findings should be interpreted as associative evidence of skin transcriptomic responses in Hu sheep under different environmental conditions—rather than as direct causal evidence that low temperature alone drove these transcriptomic differences. Full article

Opportunities abound in microfluidic technologies to impact how we understand extremely complex systems with many constituents which change with time and space. In these technologies, separation science plays a central role towards understanding everything from biology and healthcare to environmental monitoring to the search for life in the Solar system. Separations can amplify the capabilities of detection modalities by isolating targets and/or increasing their concentration while removing background constituents which can interfere with their sensing. In essence, separations increase the amount of information that can be gathered from a sample. The ideal features of next-generation separations capability are present in gradient insulator-based dielectrophoresis (g-iDEP), enabled by the length scale and precision of microfluidics. It acts through electric field interactions with particles, which enables unbiased (label-free) separations since all relevant particles, from atoms to cells, have an accessible response to electricity—either through linear (electrophoresis) or higher-order gradient (dielectrophoresis and related) effects. The technique isolates and concentrates, enabling improved detection function and multidimensional separations. Its foundational theoretical capabilities give it separations power on the order of 1:10⁸, beyond the resolving power of the best mass spectrometers and ultra-high resolution spectroscopies. Experimental evidence is amassing that shows it to be a powerful tool that can resolve tiny differences in cells (antibiotic resistance versus susceptible in unlabeled paired isolates across many species) and differentiate single-point mutations in proteins. Its capabilities are still emerging, and this work aims to quantify the current practice and connect those approaches to the ultimate capabilities of the technique towards quantifying the dynamic range and resolving power of the strategy as a whole. The technique uses two methods of quantifying the electrophysical properties of the target, voltage sweep and spatial methods. The voltage sweep method is lower-resolution and serves as a search mode, while the spatial method is higher-resolution and quantifies the properties over a smaller defined range determined via the sweep method. These quantification methods are examined by collating existing experimental data, performing relevant Monte Carlo simulations, and finite element model calculations. These are summarized to understand the mechanisms currently limiting the technique, facilitate quantitative comparisons with traditional separation science capabilities in terms of resolution and dynamic range, and compare them to the theoretical limits of the strategy. Full article

Background: Compensatory mutations offer clues in deciphering the role of a particular protein in cellular processes. Here, we investigate an unknown compensatory mutation, present in the BEAF^NP6377 fly line, that provides sufficient rescue of the defective ovary phenotype caused by null BEAF alleles to allow the maintenance of fly stocks lacking the chromatin domain insulator proteins Boundary Element-Associated Factors BEAF-32A and BEAF-32B. We call this dominant mutation Tofu. Methods: We employ both classical genetics and genomic sequencing to attempt to identify the mutation. Results: We find evidence that points to a mutation in a predicted Polycomb response element (PRE) upstream of the ribbon transcription factor gene. This may lead to aberrant rib expression, which is otherwise not expressed in adult ovaries. BEAF and Rib colocalize to a set of promoters, suggesting overlap in gene regulation. Conclusions: Tofu could be a PRE mutation leading to the aberrant activation of rib in the ovaries. This could allow Rib to compensate for a lack of BEAF to activate one or more coregulated genes necessary for egg production in flies. Full article

Adenoviral vectors are among the most efficient platforms for gene delivery; however, the level and pattern of transgene expression in these vectors are largely shaped by the viral genomic context. This review discusses the mechanisms of adenoviral transcription and alternative splicing and how they influence the expression of inserted expression cassettes. Particular attention is given to the role of insertion orientation and transgene placement within the E1 and E3 regions, as well as to the effects of viral regulatory elements, including the E1A enhancer. We analyze evidence on the use of insulating sequences to reduce nonspecific activation and improve the controllability of transgene expression. We also consider the use of endogenous adenoviral promoters—the major late promoter (MLP) and the E3 region promoter—and their contribution to enhanced transgene expression through late viral transcription. Overall, these findings support principles for the rational design of adenoviral vectors, both for high-level protein production and for building systems with regulated or tissue-specific expression. Full article

The massive influx of pelagic Sargassum in the Caribbean poses a serious environmental, social, and economic problem, as the stranded biomass is often treated as waste and deposited in landfills. This literature review synthesizes recent research highlighting its potential for valorization in various industries, turning this challenge into an opportunity. Sargassum has low levels of protein and lipids. Still, it is particularly rich in carbohydrates, such as alginates, fucoidans, mannitol, and cellulose, as well as secondary metabolites, including phenolic compounds, flavonoids, pigments, and phytosterols with antioxidant and bioactive properties. These biochemical characteristics allow for its application in renewable energy (bioethanol, biogas, biodiesel, and combustion), agriculture (fertilizers and biostimulants), construction (composite materials, cement additives, and insulation), bioremediation (adsorption of heavy metals and dyes), and in the health sector (antioxidants, anti-inflammatories, and pharmacological uses). A major limitation is its high bioaccumulation capacity for heavy metals, particularly arsenic, which increases environmental and health risks and limits its direct use in food and feed. Therefore, innovative pretreatment and bioprocessing are essential to mitigate these risks. The most promising approach for its utilization is a biorefinery model, which allows for the sequential extraction of multiple high-value compounds and energy products to maximize benefits, reduce costs, and sustainably transform Sargassum from a coastal pest into a valuable industrial resource. Full article

In healthy cells, the cytomatrix mechanics utilize mitochondrial respiration to control cytosolic motion and fine-tune the chemical processes. In cancer, the cytosolic motion is energized by glycolytic fermentation (the Warburg effect), which provides additional energy to supply the needs of the cytomatrix. Here, we describe the physical and chemical processes of the integrated and cooperative cytomatrix cytoarchitecture, in which structure and function are inseparable. The extracellular matrix is interconnected with the intracellular cytomatrix and functions as two integrated elastic solid phases. This finding led us to propose mechanisms of tumor microenvironment formation resulting from the mutational burden, in which altered proteins with corresponding post-translational modifications translocate to the cell surface, where they attract immunocompetent cells and activated fibroblasts, producing a tumor-insulating niche. This insulation disrupts cell-to-cell recognition and other signaling pathways that affect the intracellular cytomatrix, particularly actin dynamics, which influence both cell size and shape, recognized as the dedifferentiated state of cancer cells. We also discuss the perspectives of AI in cytomatrix modeling and neural network modeling, focusing on the effects of intracellular and extracellular matrices on the development of the tumor microenvironment. Full article

Finding eco-friendly alternatives to the synthetic materials used for acoustic application in building industry is necessary to address environmental sustainability. Biocomposites of natural fibers combined with a biopolymer matrix emerge as a promising approach. In this study, soy protein biocomposites were prepared with 10, 15, and 20 wt% sheep wool and were added spent coffee grounds by freeze-drying to create fibro-porous biocomposites for acoustic applications. Transmission loss (TL) measurements underlined good behavior as sound insulators, with maximum values around 22 dB at 2500 Hz and even better performance than those of commercial synthetic solutions. The obtained sound absorption coefficients were competitive, as they almost reached unity at medium and high frequencies. Airflow resistivity was determined, and values were higher for the biocomposites with coffee grounds, specifically 14–18 kPa·s·m⁻² vs. 5.62–11.6 kPa·s·m⁻². Using the input of the measured airflow resistivity, an empirical model using a genetic algorithm was developed as a prediction tool for the sound absorption performance of the samples. All in all, results showcase the feasibility of employing the studied biocomposites as competitive sound insulators and absorbers in building construction industry. Full article

The wool of sheep consists of structurally intricate natural fibres that can be processed and manufactured into a range of products. It is prized for its insulation, moisture-buffering capability, flame resistance, and biodegradability. These features arise from its unique fibre architecture and specialised protein composition, which set it apart from most other natural and synthetic fibres. However, despite these novel characteristics, wool fibre variation hampers its uses and reduces its ability to compete with other fibres. This review summarises our current knowledge of wool fibre biology. It begins with a description of wool’s functional properties and performance attributes, then explores the structural foundations of these properties, the molecular basis of fibre trait variation, and prospects for improving fibre quality using genetic approaches. Particular attention is given to the wool keratin and keratin-associated protein genes, their spatiotemporal expression patterns, and genetic polymorphism that may influence fibre characteristics. Opportunities for the genetic improvement of sheep are discussed, including the use of genetic modification and marker-assisted selection. Challenges in interpreting gene–trait associations, particularly from high-throughput omics studies, are highlighted, along with the need for functionally validated genetic markers. Potential trade-offs between wool characteristics and other production and reproductive traits are considered, emphasising the need for balanced breeding approaches. By integrating insights from structural biology, molecular genetics, and breeding strategies, this review provides a foundation for wool fibre improvement. Full article

Myelin is a lipid-rich membrane that insulates axons, providing support and ensuring efficient nerve impulse conduction. Disruption of this sheath, or demyelination, impairs neural transmission and underlies symptoms like vision loss and muscle weakness in multiple sclerosis (MS). Despite extensive studies using in vitro and in vivo models, the molecular mechanisms driving demyelination remain incompletely understood. To investigate the role of myelin basic protein (MBP) in membrane stability, we prepared model myelin membranes (MMMs) from lipids expectedly undergoing gel-to-fluid phase transition, mimicking both normal and altered myelin, with and without MBP. Differential scanning calorimetry (DSC) revealed that MBP suppresses the main phase transition in normal MMMs, unlike in modified MMMs. FTIR spectra showed strengthening of van der Waals interactions in normal MMMs with MBP upon heating and opposite effects in the analogous modified MMM system. Additionally, phosphate groups were identified as critical sites for MBP–lipid interactions. Circular dichroism (CD) spectroscopy suggests that MBP adopts helical structures that penetrate the bilayer of normal MMMs. These findings offer new insights into the molecular-level interactions between MBP and myelin membranes, with implications for understanding demyelination in diseases like MS. Full article

Schwann cells (SCs) are the primary glial cells of the Peripheral Nervous System (PNS), which insulate and provide protection and nutrients to the axons. Technological and experimental advances in neuroscience, focusing on the biology of SCs, their interactions with other cells, and their role in the pathogenesis of various diseases, have paved the way for exploring new treatment strategies that aim to harness the direct protective or causative properties of SCs in neurological disorders. SCs express cytokines, chemokines, neurotrophic growth factors, matrix metalloproteinases, extracellular matrix proteins, and extracellular vesicles, which promote the inherent potential of the injured neurons to survive and accelerate axonal elongation. The ability of SCs to support the development and functioning of neurons is lost in certain hereditary, autoimmune, metabolic, traumatic, and toxic conditions, suggesting their role in specific neurological diseases. Thus, targeting, modifying, and replacing SC strategies, as well as utilizing SC-derived factors and exosomes, have been considered novel therapeutic opportunities for neuropathological conditions. Preclinical and clinical data have demonstrated that SCs and SC-derived factors can serve as viable cell therapy for reconstructing the local tissue microenvironment and promoting nerve anatomical and functional recovery in both peripheral and central nerve injury repair, as well as in peripheral neuropathies. However, despite the promising successes of genetic engineering of SCs, which are now in preclinical and clinical trials, improving tactics to obtain ‘repair’ SCs and their products from different sources is the key goal for future clinical success. Finally, further development of innovative therapeutic approaches to target and modify SC survival and function in vivo is also urgently needed. Full article

Lipids, together with water and proteins, constitute the essential structure of cell membranes, and in the CNS, critically contribute to the production, function, and maintenance of the myelin sheath. Myelin produced by oligodendrocytes (OLs) acts as an electric insulator and assures proper conduction of information. Three major fractions of myelin lipids are cholesterol, phospholipids, and glycolipids. These lipids not only sculpt the myelin landscape as a structural support for proteins, but they also play a crucial role in molecular interactions underlying processes of protein trafficking and signal transductions. The high lipid content of myelin makes it susceptible to lipid metabolism disorders. Disorders in systemic and local lipid metabolism may lead to loss of myelin integrity and stability, and potentially to CNS demyelination seen in neurodegenerative diseases, notably progressive multiple sclerosis, for which there are few effective therapies. Precise interactions among disorders in lipid metabolism, function of oligodendrocytes, and demyelination/remyelination events, including de novo myelin formation and myelin remodeling processes, may lay the foundation for novel therapeutics for progressive MS and other demyelinating CNS conditions. Full article

Buildings represent approximately 40% of the total energy consumption. Net-zero energy buildings (NZEBs) have lower energy demands than conventional buildings due to improved thermal insulation combined with other passive design strategies. Thermal mortars, used in insulating plasters, help improve buildings’ energy efficiency in a cost-effective manner, with minimal added thickness, even on irregular surfaces. Brewer’s spent grain (BSG) accounts for 85% of the total by-products of the brewing industry. It is a cellulosic wood material, with a composition rich in protein (20%) and fiber (70%). Considering these properties, it has potential for use as a natural aggregate in mortars and as a sustainable material for buildings aligned with circular economy principles. This work aims to characterize BSG as a natural by-product for use in thermal mortars and identify different incorporation percentages. First, BSG was characterized in terms of its water content, particle size and volume mass. Then, mortars with BSG and fine sand, with different water contents, were produced and compared to a reference mortar and two commercially available thermal mortars. The performance of the mixtures was evaluated in terms of water absorption, mechanical behavior (namely, compressive and flexural strength) and thermal behavior. BSG mortars with a 0.25 w/c ratio presented a water absorption coefficient similar to that of the reference mortar. Overall, BSG mortars presented a mechanical strength profile similar to that of conventional thermal mortars. In the thermal test, the best BSG mortar (BSG75-w/c-0.25) achieved a stationary temperature difference between surfaces that was 8% lower than that of a commercial thermal mortar and 110% higher than that of the reference mortar. In sum, the best BSG mortars had a lower w/c ratio. Full article

Silica-modified electrodes possess physicochemical properties that make them valuable in electrochemical sensing and energy-related applications. Although intrinsically insulating, silica thin films can selectively interact with redox species, producing sieving effects that enhance electrochemical responses. We synthesized Class I hybrid silica matrices incorporating either negatively charged poly(4-styrene sulfonic acid) or positively charged poly(diallyl dimethylammonium chloride). These hybrid films were deposited onto ITO electrodes and evaluated via cyclic voltammetry in aqueous ferrocenium solutions. The polyelectrolyte charge played a key role in the electroassisted incorporation of ferrocene: silica-PSS films promoted accumulation, while silica-PDADMAC films hindered it due to electrostatic repulsion. In situ UV-vis spectroscopy confirmed that only a fraction of the embedded ferrocene was electroactive. Nevertheless, this fraction enabled effective mediated detection of cytochrome c in solution. These findings highlight the crucial role of ionic interactions and hybrid composition in electron transfer to redox proteins, providing valuable insights for the development of advanced bioelectronic sensors. Full article

Background/Objectives: Ischemic time plays a crucial role in graft function and survival during kidney transplantation. Cooling methods, including cold perfusion and ice slush, are predominantly applied to preserve the kidney, but they may cause uneven cooling and complications. The Organ Pocket^®, an insulated gel bag, has been introduced as an alternative cooling method. However, no studies have compared renal temperature changes between the Organ Pocket^® and conventional cooling methods. Methods: We retrospectively analyzed 49 cases of living-donor kidney transplantation. Among these, 33 received kidney grafts preserved with the Organ Pocket^® (OP group), and 16 underwent conventional cooling (control group). Renal surface temperatures were recorded at 5 min intervals during vascular anastomosis using thermography. Postoperative renal function was assessed with estimated glomerular filtration rate (eGFR), serum creatinine (sCr), and liver-type fatty acid-binding protein (L-FABP) levels. Results: The OP group demonstrated significantly higher renal surface temperatures than the control group during vascular anastomosis (p < 0.05). Renal surface temperature before reperfusion was 20.4 °C ± 2.5 °C and 17.2 °C ± 2.5 °C in the OP and control groups, respectively. No significant differences in postoperative eGFR, sCr, and L-FABP levels; delayed graft function (DGF); or acute rejection rates were observed between the groups. Conclusions: The Organ Pocket^® effectively stabilized renal temperatures during vascular anastomosis without direct cooling, thereby reducing continuous manual cooling requirements. Short-term renal function outcomes were comparable between groups; however, the Organ Pocket^® may improve surgical efficiency and be particularly beneficial in robot-assisted kidney transplantation. Further studies are warranted to investigate its long-term benefits. Full article