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ObjectiveBeta cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In recent years, the role played by beta cells in the development of T1D has evolved from passive victims of the immune system to active contributors in their own destruction. We and others have demonstrated that perturbations in the islet microenvironment promote endoplasmic reticulum (ER) stress in beta cells, leading to enhanced immunogenicity. Among the underlying mechanisms, secretion of extracellular vesicles (EVs) by beta cells has been suggested to mediate the crosstalk with the immune cell compartment.MethodsTo study the role of cellular stress in the early events of T1D development, we generated a novel cellular model for constitutive ER stress by modulating the expression of HSPA5, which encodes BiP/GRP78, in EndoC-βH1 cells. To investigate the role of EVs in the interaction between beta cells and the immune system, we characterized the EV miRNA cargo and evaluated their effect on innate immune cells.ResultsAnalysis of the transcriptome showed that HSPA5 knockdown resulted in the upregulation of signaling pathways involved in the unfolded protein response (UPR) and changes the miRNA content of EVs, including reduced levels of miRNAs involved in IL-1β signaling. Treatment of primary human monocytes with EVs from stressed beta cells resulted in increased surface expression of CD11b, HLA-DR, CD40 and CD86 and upregulation of IL-1β and IL-6.ConclusionThese findings indicate that the content of EVs derived from stressed beta cells can be a mediator of islet inflammation.

Objective: Beta cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In recent years, the role played by beta cells in the development of T1D has evolved from passive victims of the immune system to active contributors in their own destruction. We and others have demonstrated that perturbations in the islet microenvironment promote endoplasmic reticulum (ER) stress in beta cells, leading to enhanced immunogenicity. Among the underlying mechanisms, secretion of extracellular vesicles (EVs) by beta cells has been suggested to mediate the crosstalk with the immune cell compartment. Methods: To study the role of cellular stress in the early events of T1D development, we generated a novel cellular model for constitutive ER stress by modulating the expression of HSPA5, which encodes BiP/GRP78, in EndoC-βH1 cells. To investigate the role of EVs in the interaction between beta cells and the immune system, we characterized the EV miRNA cargo and evaluated their effect on innate immune cells. Results: Analysis of the transcriptome showed that HSPA5 knockdown resulted in the upregulation of signaling pathways involved in the unfolded protein response (UPR) and changes the miRNA content of EVs, including reduced levels of miRNAs involved in IL-1β signaling. Treatment of primary human monocytes with EVs from stressed beta cells resulted in increased surface expression of CD11b, HLA-DR, CD40 and CD86 and upregulation of IL-1β and IL-6. Conclusion: These findings indicate that the content of EVs derived from stressed beta cells can be a mediator of islet inflammation. [ABSTRACT FROM AUTHOR]

Heeding calls to examine multiple protective factors within single studies, this study tested whether resilience uniquely predicted higher life satisfaction and lower depression over the predictive ability of generalized self-efficacy (GSE) and mindfulness among 332 university students. A second purpose was to test whether resilience uniquely buffered the relationship between two forms of stress—cumulative stress from particular negative life events and general perceived stress—and both life satisfaction and depression over the buffering ability of GSE and mindfulness. In hierarchical multiple regressions, resilience uniquely predicted 3% of the variance in satisfaction with life and 1% of the variance in depression. GSE and mindfulness buffered the relationship between cumulative negative life event stress and depression. At higher levels of GSE and mindfulness, the relationship between cumulative negative life event stress and depression was weaker. [ABSTRACT FROM AUTHOR]

Here, a combination of dopamine self-polymerization and epoxy modified SiO 2 (M-SiO 2 ) grafting was proposed, with the purpose of increasing interfacial adhesion of UHMWPE fiber. Inspired by mussel adhesion, polydopamine (PDA) was deposited onto the surface of UHMWPE fiber to form a thin layer with amino and hydroxyl groups. M-SiO 2 nanoparticles were then adhered to fiber surface via chemical reactions by a "two-step" or "one-step" technology. In the "two-step" technique, the M-SiO 2 nanoparticles were adhered to the surface of PDA modified UHMWPE fiber via reactions between epoxy and amino groups. In the "one-step" method, M-SiO 2 and dopamine were added into the UHMWPE/Tris solution at the same time. Surface morphology and thermal properties of various UHMWPE fibers were tested by SEM and TGA, respectively. Surface wettability of different UHMWPE fibers were evaluated by dynamic contact angle. The results proved that PDA and M-SiO 2 were successfully adhered to the surface of UHMWPE fibers. The mechanical property of modified UHMWPE/Epoxy composites was investigated, and 43.7 % improvement was obtained, compared with unmodified UHMWPE/Epoxy composite. Additionally, micro-bond test revealed that the interfacial property (IFSS value) of modified UHMWPE fiber via the "one-step" method was 6.08 MPa, significantly higher than that of unmodified UHMWPE fiber (2.47 MPa)., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Recent advances in electron microscopy techniques have led to a significant scale up in volumetric imaging of biological tissue. The throughput of electron microscopes, however, remains a limiting factor for the volume that can be imaged in high resolution within reasonable time. Faster detection methods will improve throughput. Here, we have characterized and benchmarked a novel detection technique for scanning electron microscopy: optical scanning transmission electron microscopy (OSTEM). A qualitative and quantitative comparison was performed between OSTEM, secondary and backscattered electron detection and annular dark field detection in scanning transmission electron microscopy. Our analysis shows that OSTEM produces images similar to backscattered electron detection in terms of contrast, resolution and signal-to-noise ratio. OSTEM can complement large scale imaging with (scanning) transmission electron microscopy and has the potential to speed up imaging in single-beam scanning electron microscope., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacob Hoogenboom reports a relationship with Delmic BV that includes: equity or stocks., (Copyright © 2023. Published by Elsevier B.V.)

Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)