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Communicating Genetic Information in Families with Inherited Late-Onset Neurodegenerative Diseases: A Scoping Review

2026-03-27T07:39:58Z

Title: Communicating Genetic Information in Families with Inherited Late-Onset Neurodegenerative Diseases: A Scoping Review Abstract: Communicating genetic information within families living with inherited genetic conditions (IGCs), especially incurable and progressive late-onset neurodegenerative diseases (LONDs), presents significant challenges. To date, no literature review has specifically addressed this issue in families with LONDs. To fill this gap, a scoping review was conducted following PRISMA and JBI guidelines. Four databases (Scopus, Web of Science, PubMed, and PsycInfo) were searched, resulting in 31 articles for analysis. Six categories were identified: (i) from whom to whom: communication transmitters and receivers, (ii) what to tell: content and details of communication, (iii) how to tell: communication approach, (iv) when to tell: timing of communication, (v) barriers and reasons for not communicating, and (vi) facilitators and reasons for communicating. Sharing information about LONDs is a multi-step, deliberative process involving several transmitters and receivers. It typically begins with first-degree relatives, with women often assuming a pivotal role in the gathering and dissemination of information, and extends to the wider family. This process includes assessing the family member’s subjective experiences and the potential impact of the information. Fear of stigmatization and discrimination are notable barriers, while feelings of responsibility and moral obligation toward family members are strong motivators for transmitters to communicate. The studies included in this review were all retrospective, primarily utilized a qualitative design, and predominantly focused on families with Huntington's disease. Prospective studies are needed to investigate disclosure decision-making in families with other LONDs and to explore how the potential availability of clinical trials for testing new drugs might influence family communication.

Activation of nuclear receptors correlates with tuberculosis severity and is a target for host-directed therapy

2026-03-27T16:21:44Z

Title: Activation of nuclear receptors correlates with tuberculosis severity and is a target for host-directed therapy Abstract: Introduction: The immune response to Mycobacterium tuberculosis is accompanied by metabolic adaptations that fuel host immunity, but that are exploited by the pathogen to ensure persistence and growth. Activation of nuclear receptors, such as liver-X-receptors (LXR), orchestrate macrophage immunometabolic adaptations to infection and globally associate with tuberculosis (TB) protection. Methods: We interrogated available transcriptomic datasets of whole blood from TB patients or M. tuberculosis aerosol-infected mice to assess the expression of the signal by nuclear receptors (SNR) and LXR pathways and its correlation with disease severity. In vitro (macrophages) and in vivo (mouse model) M. tuberculosis infections were used for functional validation of the LXR act as a potential host-directed therapy. Results: We show that both the SNR and the LXR pathways are detected in the whole blood of TB patients and that their expression correlates with disease severity. Accordingly, the activation of the LXR pathway progressively increases in the lungs of M. tuberculosis-infected C57BL/6 and C3HeB/FeJ mice. Pharmacologic activation of LXR, specifically at the chronic stage of infection, improved infection outcomes and significantly prolonged the survival of the highly susceptible C3HeB/FeJ mice. Common to both mouse models and to in vitro macrophage infections, LXR activation enhanced bacterial control together with an increase in extracellular cholesterol levels. Discussion: We propose that progressive LXR activation is required to fine-tune host cholesterol availability during M. tuberculosis infections and restrict access to this nutrient during chronic stages of infections. Collectively, we identify the SNR/LXR pathways as potential biomarkers of TB severity and timely LXR activation as a candidate host-directed therapy.

Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity

2026-03-27T07:39:56Z

Title: Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity Abstract: Introduction: During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Mycobacterium tuberculosis may colonize the BM, studies using the mouse model of infection and the laboratory reference strain M. tuberculosis H37Rv have demonstrated limited emergency myelopoiesis and trained immunity. Methods: To further address this issue, we aerosol- infected C57BL/6 mice with high doses of the hypervirulent M. tuberculosis isolate HN878 and monitored alterations to the BM. This experimental model better resembles the human blood immune signature of TB. Results and discussion: We found increased frequencies of lineage^-Sca-1⁺cKit⁺ (LSK) cells and the granulocyte/macrophage progenitor (GMP) population. At the mature cell level, we observed an increase of monocytes and neutrophils in the blood and lung, likely reflecting the increased BM myeloid output. Monocytes or monocyte-derived macrophages recovered from the BM of M. tuberculosis HN878-infected mice did not show signs of trained immunity, suggesting an uncoupling of emergency myelopoiesis and trained immunity in the BM. Surprisingly, M. tuberculosis HN878-induced emergency myelopoiesis was not fully dependent on IFNγ, as mice lacking this cytokine and infected under the same conditions as wild-type mice still presented BM alterations. These data expand our understanding of the immune response to M. tuberculosis and raise awareness of pathogen strain-imposed differences to host responses.

Decellularised Cartilage-Based Hydrogels Functionalised With Chondroitin Sulphate and Quercetin: The Impact on Chondrogenesis

2026-03-27T17:41:07Z

Title: Decellularised Cartilage-Based Hydrogels Functionalised With Chondroitin Sulphate and Quercetin: The Impact on Chondrogenesis Abstract: Tissue engineering and regenerative medicine approaches are being actively developed for degenerative disorders, including osteoarthritis (OA). Decellularized matrix (dECM) is a promising biomaterial; however, glycosaminoglycan (GAG) loss during decellularization limits its chondrogenic potential. In this study, we aimed to overcome this by developing a dECM hydrogel originating from cartilage, functionalized with the GAG chondroitin sulphate (CS), to replenish those originally depleted and incorporating quercetin to enhance hydrogel properties and chondrogenesis. An optimized decellularization protocol efficiently removed DNA, but with a significant loss of GAGs (73%). After dECM solubilization, functionalization with CS or aldehyde modified CS (mCS) was performed. CS-functionalized hydrogels maintained low stiffness compared to non-functionalized hydrogel, while 0.2 mg/mL mCS hydrogels exhibited significantly slower gelation kinetics. To aid the hydrogel's chondrogenic ability, a novel approach using quercetin was investigated. Incorporation of 0.3 mg/mL quercetin in 0.4 mg/mL mCS-functionalized hydrogels resulted in increased gel stiffness. The impact on cell viability and chondrogenic differentiation was evaluated. Results showed similar cell viability in dECM and CS-functionalized hydrogels at 1 and 3 days of culture, with no significant changes in gene expression of chondrogenic and hypertrophic genes. In quercetin-containing hydrogels, the viability of human dermal fibroblasts was not significantly different from non-functionalized hydrogels, while human chondrocytes showed a significant upregulation of collagen type II, with 6.6- and 2.2-fold increases for 0.15 and 0.3 mg/mL quercetin, respectively. These results provide an initial proof-of-concept for dECM functionalization strategies that restore lost CS while incorporating quercetin, creating a microenvironment favorable for cartilage repair.

Genetically Diverse Mycobacterium tuberculosis Isolates Manipulate Inflammasome and Interleukin 1β Secretion Independently of Macrophage Metabolic Rewiring

2026-03-27T15:31:53Z

Title: Genetically Diverse Mycobacterium tuberculosis Isolates Manipulate Inflammasome and Interleukin 1β Secretion Independently of Macrophage Metabolic Rewiring Abstract: The diversity of Mycobacterium tuberculosis impacts the outcome of tuberculosis. We previously showed that M. tuberculosis isolates obtained from patients with severe disease induced low inflammasome activation and interleukin 1β (IL-1β) production by infected macrophages. Here we questioned whether this differential modulation of macrophages by M. tuberculosis isolates depended on distinct metabolic reprogramming. We found that the macrophage metabolic landscape was similar regardless of the infecting M. tuberculosis isolate. Paralleling single–Toll-like receptor (TLR) activated macrophages, glycolysis inhibition during infection impaired IL-1β secretion. However, departing from TLR -based models, in infected macrophages, IL-1β secretion was independent of mitochondrial metabolic changes and hypoxia-inducible factor 1α (HIF-1α). Additionally, we found an unappreciated impact of a host metabolic inhibitor on the pathogen, and show that inflammasome activation and IL-1β production by macrophages require metabolically active bacteria. Our study highlights the potential confounding effect of host metabolic inhibitors on the pathogen and uncoupling of M. tuberculosis-inflammasome modulation from the host metabolic reprogramming.

Immunoinformatics Predictions on Variable Mycobacterium tuberculosis Lineage 6 T Cell Epitopes and HLA Interactions in West Africa

2026-03-27T07:39:52Z

Title: Immunoinformatics Predictions on Variable Mycobacterium tuberculosis Lineage 6 T Cell Epitopes and HLA Interactions in West Africa Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge. The human-adapted TB-causing bacteria are distributed into ten lineages with distinct global distributions and clinical outcomes. Mtb lineages 4 (L4) and L6 are good prototypes of these differences, because L4 is globally prevalent, whereas L6 is geographically restricted to West Africa and associated with slower disease progression. Given the fundamental role of T cells for the control of TB, we questioned whether Mtb L4 or L6 antigens and HLA interactions would be disrupted in West African hosts. Here, we selected variable and validated antigens and demonstrate their expression during in vivo Mtb L4 or L6 infections. We then compared the predicted number of IFN-γ-inducing and HLA high-binding-affinity peptides in Mtb ancestral, L4, or L6 proteins, considering HLA alleles of high or low frequency in West Africa. Our immunoinformatics approach predicts that non-synonymous substitutions of high variance in Mtb L6 strains diminish binding affinities to HLA alleles prevalent in West African populations, suggesting specific adaptations of these strains to their preferred hosts. Future functional studies will advance our knowledge on lineage-specific evolution and inform strategies to enhance TB control in endemic regions.

Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker

2026-03-27T07:39:49Z

Title: Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker Abstract: Colorectal cancer (CRC) has been addressed in the framework of molecular, cellular biology, and biochemical traits. A new approach to studying CRC is focused on the relationship between biochemical pathways and biophysical cues, which may contribute to disease understanding and therapy development. Herein, we investigated the mechanical properties of CRC cells, namely, HCT116, HCT15, and SW620, using static and dynamic methodologies by atomic force microscopy (AFM). The static method quantifies Young’s modulus; the dynamic method allows the determination of elasticity, viscosity, and fluidity. AFM results were correlated with confocal laser scanning microscopy and cell migration assay data. The SW620 metastatic cells presented the highest Young’s and storage moduli, with a defined cortical actin ring with distributed F-actin filaments, scarce vinculin expression, abundant total focal adhesions (FAK), and no filopodia formation, which could explain the lessened migratory behavior. In contrast, HCT15 cells presented lower Young’s and storage moduli, high cortical tubulin, less cortical F-actin and less FAK, and more filopodia formation, probably explaining the higher migratory behavior. HCT116 cells presented Young’s and storage moduli values in between the other cell lines, high cortical F-actin expression, intermediate levels of total FAK, and abundant filopodia formation, possibly explaining the highest migratory behavior.

Microrheological comparison of melanoma cells by atomic force microscopy

2026-03-27T07:39:49Z

Title: Microrheological comparison of melanoma cells by atomic force microscopy Abstract: Melanoma is one of the most severe cancers due to its great potential to form metastasis. Recent studies showed the importance of mechanical property assessment in metastasis formation which depends on the cytoskeleton dynamics and cell migration. Although cells are considered purely elastic, they are viscoelastic entities. Microrheology atomic force microscopy (AFM) enables the assessment of elasticity and viscous properties, which are relevant to cell behavior regulation. The current work compares the mechanical properties of human neonatal primary melanocytes (HNPMs) with two melanoma cell lines (WM793B and 1205LU cells), using microrheology AFM. Immunocytochemistry of F-actin filaments and phosphorylated focal adhesion kinase (p-FAK) and cell migration assays were performed to understand the differences found in microrheology AFM regarding the tumor cell lines tested. AFM revealed that HNPMs and tumor cell lines had distinct mechanical properties. HNPMs were softer, less viscous, presenting a higher power-law than melanoma cells. Immunostaining showed that metastatic 1205LU cells expressed more p-FAK than WM793B cells. Melanoma cell migration assays showed that WM73B did not close the gap, in contrast to 1205LU cells, which closed the gap at the end of 23 h. These data seem to corroborate the high migratory behavior of 1205LU cells. Microrheology AFM applied to HNPMs and melanoma cells allowed the quantification of elasticity, viscous properties, glassy phase, and power-law properties, which have an impact in cell migration and metastasis formation. AFM study is important since it can be used as a biomarker of the different stages of the disease in melanoma.

Addressing family communication in genetic counseling: A scoping review of process studies

2026-03-27T07:39:48Z

Title: Addressing family communication in genetic counseling: A scoping review of process studies Abstract: Process studies explore the content and dynamics established during genetic counseling (GC), allowing a greater understanding of what happens. No literature review has specifically examined how family communication of genetic information has been addressed in GC process studies. To fill this gap, a scoping review was conducted. Scopus, Web of Science, PubMed, and PsycInfo were searched, resulting in 21 articles for analysis. Most studies were retrospective (n = 19) and qualitative (n = 15) and involved hereditary cancer syndromes (n = 13). Studies analyzed how family communication of genetic information is addressed in GC by either focusing on patients' experiences and perspectives, or genetic healthcare professionals' (GHP) roles and scope of practice. All studies reported that GHP address family communication with patients, but their practices were heterogeneous and influenced by contextual factors. Practices to address family communication included providing guidance to inform the family (n = 19), materials to support communication (n = 16), psychosocial assessment (n = 11), and additional support (n = 18). Our findings suggest that the approach to family communication in GC draws on both teaching and counseling models, although with greater emphasis on the former. This is consistent with integrated models of GC. Future prospective process studies using observational data could enhance our understanding of patient-professional interactions and their influence on patient decision-making regarding family communication of genetic information.

Corrosion and tribocorrosion behavior of micro-arc oxidized titanium surfaces functionalized with poly(ethylene glycol) and antimicrobial peptides

2026-03-21T07:54:26Z

Title: Corrosion and tribocorrosion behavior of micro-arc oxidized titanium surfaces functionalized with poly(ethylene glycol) and antimicrobial peptides Abstract: This paper investigates the corrosion and tribocorrosion behavior of titanium surfaces treated with micro-arc oxidation (MAO) and further functionalized with poly(ethylene glycol) (PEG) and an antimicrobial peptide (AMP). PEG was first covalently conjugated onto the MAO surfaces followed by AMP physical adsorption. The MAO layer maintained its porosity and bulk chemical composition (Ca+P) after surface functionalization with PEG-AMP. Although no significant differences on the corrosion mechanisms were observed, the corrosion resistance of the MAO surfaces was slightly improved by the presence of PEG-AMP. This corrosion improvement was mainly attributed to the outer porous oxide layer, where PEG-AMP may create a barrier between the MAO layer and the corrosive medium. In addition, although coefficient of friction (COF) has been slightly increased on the PEG-AMP functionalized MAO surfaces, the bulk titanium was effectively protected under loading and reciprocating sliding conditions, which demonstrates a good tribocorrosion behavior.

Polysaccharide-mediated stabilization of bacterial nanocellulose dispersions: Experimental and molecular dynamics study

2026-03-21T07:50:26Z

Title: Polysaccharide-mediated stabilization of bacterial nanocellulose dispersions: Experimental and molecular dynamics study Abstract: Colloidal dispersions of pristine cellulose (nano- or microsized; fibrillar or particulate), are typically unstable in water due to interfiber/interparticle interactions. Carboxymethyl cellulose (CMC) is known to effectively sta-bilize these dispersions, allowing for full recovery of the properties upon redispersion after drying. However, the underlying mechanism has been unclear. This study investigated why CMC effectively stabilized cellulose and whether other polysaccharides could perform similarly. Mixtures of bacterial nanocellulose (BNC) with chia mucilage (ChM), hyaluronic acid (HA), pectin (Pec), xanthan gum (XG), locust bean gum (LBG), salep, alginate (Alg), and polyol glycerol (Gly) were compared to mixtures of BNC:CMC. The stability and redispersibility after drying of each mixture were analyzed. Only ChM produced homogeneous and stable BNC dispersions similar to CMC. The polysaccharides’ adsorption onto cellulose films was studied using quartz crystal microbalance with dissipation (QCM-D). CMC and ChM showed stronger and more stable adsorption, with higher retained mass after washing (10.0 ± 0.3 and 7.8 ± 2.3 mg/m2, respectively), compared to Alg, HA, or XG (3.6 ± 0.6, 1.0 ± 0.3 and 0.2 ± 0.1 mg/m2, respectively). Molecular dynamics simulations confirmed the stronger interactions of CMC and ChM with cellulose surfaces, characterized by hydrogen bonding and perpendicular orientation.

Impaired Acetyl-CoA Compartmentalization Drives a Futile Lipogenic–Oxidative Cycle in N88S Seipinopathy

2026-03-21T07:45:45Z

Title: Impaired Acetyl-CoA Compartmentalization Drives a Futile Lipogenic–Oxidative Cycle in N88S Seipinopathy Abstract: The N88S mutation in human seipin causes a dominant motor neuron disease marked by ER stress and inclusion body formation, lipid imbalance, and oxidative damage. However, the metabolic mechanisms connecting these defects remain poorly understood. Previous proteomic profiling in our yeast model of N88S human seipinopathy revealed decreased protein levels of enzymes involved in the tricarboxylic acid cycle, fatty acid and carboxylic acid metabolism, and the glyoxylate cycle, suggesting impaired downstream utilization of peroxisome-derived acetyl-CoA. Guided by these findings, we investigated how peroxisomal function contributes to cellular dyshomeostasis. N88S seipin-expressing cells exhibited increased peroxisome abundance but defective routing of acetyl-CoA into mitochondrial and glyoxylate pathways, resulting in elevated reactive oxygen species (ROS), impaired glyoxylate cycle activation, and reduced metabolic adaptability to nonfermentable carbon sources. Loss of peroxisomes or forced cytosolic redirection of acetylCoA further exacerbated ER stress, ROS accumulation, lipid peroxidation, and the growth defect on N88S seipin-expressing cells, whereas inhibition of fatty acid synthesis mitigated oxidative damage. These findings demonstrate that N88S seipin triggers a futile cycle in which misrouted cytosolic acetyl-CoA drives lipogenesis, amplifying oxidative damage and ER stress. We conclude that defective peroxisome–mitochondria metabolic coupling and acetyl-CoA misrouting may represent central pathogenic mechanisms driving cellular dysfunction in N88S-linked seipinopathy.

Exploring immobilization strategies of antimicrobial peptides onto MAO-treated titanium to fight MRSA colonization and preserve osteogenic activity

2026-03-19T07:49:49Z

Title: Exploring immobilization strategies of antimicrobial peptides onto MAO-treated titanium to fight MRSA colonization and preserve osteogenic activity Abstract: Alternative therapies to systemic antibiotics are increasingly explored to prevent infections associated with boné implants. Among them, the surface functionalization of titanium with antimicrobial peptides (AMP) is particu-larly promising due to their broad-spectrum activity and low risk of inducing bacterial resistance. However, a critical challenge remains in achieving both effective antibacterial action and the promotion of osseointegration. This proof-of-concept study investigates different strategies for immobilizing AMP onto bioactive micro-arcoxidation (MAO) coatings on titanium, aiming to combat methicillin-resistant Staphylococcus aureus (MRSA) colonization while preserving the osseointegration potential of MAO surfaces. The peptide MSI-78 was immo-bilized either by physical adsorption or covalent grafting, using 1,1′-carbonyldiimidazole (CDI) coupling agent or poly(ethylene glycol) (PEG) spacer. All immobilization strategies preserved the heterogeneous porous archi-tecture and calcium/phosphorus doping of the complex MAO coatings. Prior to bacterial incubation, the surfaces were pre-conditioned with human plasma proteins. MSI-78, whether by physical adsorption or covalent grafting, killed MRSA after 5 h, but also promoted bacterial adhesion to the surface. In contrast, the combined strategy of grafted PEG and physically adsorbed AMP promoted a remarkable antibacterial effect, by reducing MRSA colonization and killing about 80% of adherent bacteria. Regardless of the immobilization strategy, bacterial killing appeared to occur via contact-mediated membrane disruption. Moreover, these PEGylated MAO surfaces with adsorbed AMP maintained excellent cytocompatibility with bone-like cells and supported osteogenicresponse, underscoring their potential as bioactive coatings for titanium implants.

Rhamnose biosynthesis is not impaired by the deletion of putative rfbC genes, slr0985 and slr1933, in Synechocystis sp. PCC 6803

2026-02-26T07:13:19Z

Title: Rhamnose biosynthesis is not impaired by the deletion of putative rfbC genes, slr0985 and slr1933, in Synechocystis sp. PCC 6803 Abstract: Cyanobacterial extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides can be attached to the cell wall as capsular polysaccharides (CPS) or released to the environment as released polysaccharides (RPS). These polymers have an unusually high diversified monosaccharidic composition, making them attractive for biotechnological/biomedical applications. However, their production is still poorly understood, hindering their optimization for industrial needs. This work aimed to better understand the biosynthesis of the 6-deoxy sugars, fucose and rhamnose, in the model cyanobacterium Synechocystis sp. PCC 6803. To that end, genes encoding proteins putatively involved in the biosynthesis of GDP-L-fucose [sll1213 (fucS)] and dTDP-L-rhamnose [slr0985 (rfbC1) and slr1933 (rfbC2)] were deleted. As previously observed, ΔfucS had significant growth impairment, and its RPS did not contain any fucose or rhamnose. Here, we also showed that both deoxyhexoses’ pathways are completely impaired in ΔfucS. In contrast, both ΔrfbC1 and ΔrfbC1ΔrfbC2, although producing significantly less RPS and more CPS than the wild type, did not show major differences regarding the RPS monosaccharidic composition. These results strongly suggest that their gene products are not essential for rhamnose biosynthesis. Transcriptional analysis revealed that one of the gmd genes (slr1072) putatively encoding a GDP-mannose 4,6-dehydratase was upregulated in all the knockout strains and that the three EPS-related genes in the same operon as rfbC1 (slr0982, slr0983, and slr1610) were upregulated in both ΔrfbC strains. Altogether, our results reveal that rhamnose biosynthesis in Synechocystis depends on FucS but not on the putative RfbC enzymes, underlining the need to further elucidate the mechanisms involved in the biosynthesis of this deoxyhexose. IMPORTANCE This study contributes to the overall knowledge of deoxyhexoses’ biosynthesis in Synechocystis sp. PCC 6803. Here, we demonstrated that the ΔfucS strain not only produces EPS without fucose and rhamnose, but that both pathways are completely impaired. Furthermore, we also showed that the deletion of both putative rfbC genes does not affect rhamnose biosynthesis despite having an impact on carbohydrate production/export, shifting RPS to CPS production. Altogether, our results suggest that the rfbC genes are not correctly annotated and highlight the intricacies and/or potential crosstalk between the two deoxyhexose pathways, yet to be completely unraveled in Synechocystis. The understanding of the cyanobacterial EPS assembly and export is crucial for the optimization of their production and tailoring for industrial/commercial applications.

Bioabsorbable Endovascular Adhesive Tape (BEAT) for Improving Vascular Regeneration

2026-03-17T07:45:01Z

Title: Bioabsorbable Endovascular Adhesive Tape (BEAT) for Improving Vascular Regeneration Abstract: The drug-coated balloons (DCBs) provide a combination therapy of balloon angioplasty and anti-proliferative drug delivery totarget lesions, thereby facilitating the appealing concept of leaving nothing behind. However, several studies have highlightedsignificant challenges posed by low drug transfer efficiency and immediate lumen loss due to elastic recoil. Herein, we propose abioabsorbable endovascular adhesive tape (BEAT) platform that can realize robust adhesion and complete transfer after ballooninflation, enabling efficient endoluminal drug delivery while providing temporary radial support against elastic recoil. ThisBEAT coated balloon contains sprayable Janus coating layers of crosslinked drug-eluting polyelectrolyte complexes (PECs) andpoly(thioctic acid) (PTA) adhesive layer. Notably, the poly (L-lysine-co-L-leucine)-poly (acrylic acid) PECs (PKL-PAA, KLA) exhibitexceptional anti-coagulation properties and selective endothelial cell adhesion behavior. Moreover, the hydrophobic interactionand photo-controllable crosslinking of KLA PECs enable flexible mechanical tunability (0.74–10.9 MPa), robust swelling resistance,and enzyme-responsive biodegradability, thus guaranteeing temporary mechanical reinforcement for blood vessels with efficientdrug delivery. In a rat abdominal aorta injury model, this BEAT coated balloon demonstrates intact transfer with mechanicalcompliance to the vessel and effectively attenuates neointimal hyperplasia. This BEAT platform offers a promising perspective forthe development of DCBs in vascular interventions.

C.A.R.E Tutor Toolkit: Communicate, Assess, Reflect & Empower Tutors for practical classes with laboratory animals

2026-01-25T20:42:01Z

Title: C.A.R.E Tutor Toolkit: Communicate, Assess, Reflect & Empower Tutors for practical classes with laboratory animals

A conserved 3'UTR short motif regulates gene expression in vertebrates

2026-03-12T18:21:12Z

Title: A conserved 3'UTR short motif regulates gene expression in vertebrates Abstract: The messenger RNA (mRNA) 3’ untranslated region (3’UTR) contains important regulatory sequences, including upstream sequence elements(USEs), which regulate gene expression. One well-characterised USE in the 3’UTR of the Drosophila polo gene affects adult fly phenotypes whendisrupted. We have now identified a highly conserved sequence within this USE (DplUSE) in the 3’UTR of several vertebrate genes, includingin zebrafish, mouse, and human genomes and show that DplUSE enhances gene expression in human cells and zebrafish embryos. We showthat, in humans, DplUSE-containing genes are associated with congenital disease processes, and that disruption of DplUSE function impairszebrafish development. We also found that HuR/ELAVL1, hnRNPC, and PTBP1/hnRNPI bind to DplUSE RNA and are required for its activityin a human cell line, suggesting a highly conserved mechanism across distantly related species. Our results indicate that PTBP1 has a globalfunction in alternative polyadenylation, activating the selection of distal polyA sites and repressing intronic polyadenylation in DplUSE-containinggenes while hnRNPC and HuR modulate their expression. Additionally, we found that a colon cancer-associated SNP in the POU2AF2/C11orf533’UTR creates an ectopic DplUSE site, increasing gene expression in zebrafish gut cells and in a human cell line. We have therefore identified ashort 3’UTR motif present in diverse vertebrate genes that controls their expression through conserved RBPs interactions and is implicated in human disease.

N-Glycans as fundamental immune-checkpoints at the frontiers of inflammation, autoimmunity and cancer

2026-01-10T01:58:37Z

Title: N-Glycans as fundamental immune-checkpoints at the frontiers of inflammation, autoimmunity and cancer Abstract: Glycans cover the surface of essentially all cells, giving rise to the so-called glycocalyx. Glycans, and particularly N-glycans are key players in defining the fate and the nature of the immune response, participating in both pro-inflammatory and anti-inflammatory pathways occurring in inflammation, autoimmunity and cancer. Glycans and glycan-binding proteins (GBPs) are instrumental molecules that integrate the immunological landscape in homeostasis, being involved in how the host immune system perceives the self and non-self. Perturbations in these immune regulatory circuits created by glycans and GBPs may result in the loss of immune tolerance associated with autoimmunity and inflammatory conditions, but also in malignant transformation. This chapter will discuss the regulatory role played by N-glycans as fundamental immune-checkpoints in the interplay between the immune cells and their surrounding microenvironment associated with homeostasis and disease. Furthermore, we will also explore how N-glycans can act as promising diagnostic and prognostic biomarkers in disease, as well as appealing targets for new therapeutic approaches in inflammation, autoimmunity and cancer.

Directed disruption of IL2 aggregation and receptor binding sites produces designer biologics with enhanced specificity and improved production capacity

2025-12-11T07:16:46Z

Title: Directed disruption of IL2 aggregation and receptor binding sites produces designer biologics with enhanced specificity and improved production capacity Abstract: The pleotropic nature of interleukin-2 (IL2) has allowed it to be used as both a pro-inflammatory and anti-inflammatory therapeutic agent, through promotion of regulatory T cell (Treg) responses via the trimeric IL2RABG receptor or promotion of CD8 T cell responses via the dimeric IL2RBG receptor, respectively. However, the utility of IL2 as a treatment is limited by this same pleiotropy, and protein engineering to bias specificity towards either Treg or CD8 T cell lineage often requires a trade-off in protein production or total bioactivity. Here we use SolubiS and dTANGO, computational algorithm-based methods, to predict mutations within the IL2 structure to improve protein production yield in muteins with altered cellular selectivity, to generate combined muteins with elevated therapeutic potential. The design and testing process identified the V106R (murine) / V91R (human) mutation as a Treg-enhancing mutein, creating a cation repulsion to inhibit primary binding to IL2RB, with a post-IL2RA confirmational shift enabling secondary IL2RB binding, and hence allowing the trimeric receptor complex to form. In human IL2, additional N90R T131R aggregation-protecting mutations could improve protein yield of the V91R mutation. The approach also generated novel CD8 T cell-promoting mutations. Y59K created a cation-cation repulsion with IL2RA, while Q30W enhanced CD8 T cell activity through potential π-stacking enhancing binding to IL2RB, with the combination highly stimulatory for CD8 T cells. For human IL2, Y45K (homolog to murine Y59K) coupled with E62K prevented IL2RA binding, however it required the aggregation-protecting mutations of N90R T131R to rescue production. These muteins, designed with both cellular specificity and protein production features, have potential as both biological tools and therapeutics.

Reprogramming CD8+ T-cell Branched N-Glycosylation Limits Exhaustion, Enhancing Cytotoxicity and Tumor Killin

2025-10-09T06:17:57Z

Title: Reprogramming CD8+ T-cell Branched N-Glycosylation Limits Exhaustion, Enhancing Cytotoxicity and Tumor Killin Abstract: T-cell therapies have transformed cancer treatment. While surface glycans have been shown to play critical roles in regulating T-cell development and function, whether and how the glycome influences T cell–mediated tumor immunity remains an area of active investigation. In this study, we show that the intratumoral T-cell glycome is altered early in human colorectal cancer, with substantial changes in branched N-glycans. We demonstrated that CD8+ T cells expressing β1,6-GlcNAc branched N-glycans adopted an exhausted phenotype, marked by increased PD1 and Tim3 expression. CRISPR/Cas9 deletion of key branching glycosyltransferase genes revealed that Mgat5 played a prominent role in T-cell exhaustion. In culture-based assays and tumor studies, Mgat5 deletion in CD8+ T cells resulted in improved cancer cell killing. These findings prompted assessment of whether MGAT5 deletion in anti-CD19 chimeric-antigen receptor (CAR) T cells could enable this therapeutic modality in a solid tumor setting. We showed that MGAT5 KO anti-CD19-CAR T cells inhibited the growth of CD19-transduced tumors. Together, these findings show that MGAT5-mediated branched N-glycans regulate CD8+ T-cell function in cancer and provide a strategy to enhance antitumor activity of native and CAR T cells.