Simsjoseph0993

The transcriptional coregulator OCA-B promotes expression of T cell target genes in cases of repeated antigen exposure, a necessary feature of autoimmunity. We hypothesized that T cell-specific OCA-B deletion and pharmacologic OCA-B inhibition would protect mice from autoimmune diabetes. We developed an Ocab conditional allele and backcrossed it onto a diabetes-prone NOD/ShiLtJ strain background. T cell-specific OCA-B loss protected mice from spontaneous disease. Protection was associated with large reductions in islet CD8+ T cell receptor specificities associated with diabetes pathogenesis. CD4+ clones associated with diabetes were present but associated with anergic phenotypes. The protective effect of OCA-B loss was recapitulated using autoantigen-specific NY8.3 mice but diminished in monoclonal models specific to artificial or neoantigens. Rationally designed membrane-penetrating OCA-B peptide inhibitors normalized glucose levels and reduced T cell infiltration and proinflammatory cytokine expression in newly diabetic NOD mice. Together, the results indicate that OCA-B is a potent autoimmune regulator and a promising target for pharmacologic inhibition.

A new cutaneous staging system for folliculotropic mycosis fungoides (FMF) has been purported to better estimate survival compared with the staging system for conventional mycosis fungoides.

To analyze predictive variables associated with survival and evaluate the effectiveness of the newly proposed staging system for estimating overall survival and disease-specific survival (DSS) in a US cohort.

This cohort study assessed 195 patients with FMF in the dermatopathology database of the University of California, San Francisco from January 1, 1990, to April 31, 2012, for eligibility. A total of 153 patients were excluded for the following reasons (1) alternative diagnoses were favored ranging from benign dermatitides to other forms of cutaneous lymphoma; (2) technical problems with slides; and (3) lack of follow-up information. Data were analyzed from January 1, 2018, to August 31, 2020.

Kaplan-Meier curves were used to estimate overall survival and DSS for the entire cohort. Possible predictive variablesstimating survival in a US cohort; and that the poor prognosis initially associated with FMF only applies to the advanced cutaneous stage.

Cox proportional hazards regression modeling demonstrated cutaneous stage to be the only statistically significant predictive variable associated with DSS. Subdividing FMF into early and advanced cutaneous stages was associated with effective estimation of survival in this cohort. Thus, findings suggest that FMF is a heterogeneous disease with early and advanced cutaneous stages; that the new staging system is effective in estimating survival in a US cohort; and that the poor prognosis initially associated with FMF only applies to the advanced cutaneous stage.Super-aligned carbon nanotube (SACNT) films with wrinkled structures are prepared by a biaxial pre-strain method and can withstand repetitive stretching of large strains in multiple directions. Ultra-stretchable supercapacitors were fabricated with the SACNT film and active carbon (AC) powders. The initial specific capacitance without strain and with 150% strains in the X, Y and 45° axes was 91, 88, 89 and 90 F g-1, respectively. click here Moreover, the capacitance retentions were 97%, 98.5% and 98.6% after 2000 tensile cycles at 0-150% strain in the X, Y and 45° axes, respectively, demonstrating the excellent strain durability of the SACNT/AC supercapacitors. The stretchable circuit with the combination of stretchable SACNT/AC supercapacitors and SACNT conductors demonstrates a promising method in developing self-contained stretchable functional devices for a variety of applications. The low-cost and scalable biaxial pre-strain process presents a potential route for designing high performance stretchable electronic and energy storage devices.Prevailing drug delivery strategies rely on the use of synthetic nanocarriers like metal nanoparticles and polymeric liposomes to control the release of therapeutics in a safe and efficacious manner. Despite their high efficiency in encapsulating drugs, these systems exhibit low to moderate biocompatibility, low cellular uptake, and sub-optimal targeting capabilities. Conversely, cell-derived nanoparticles (CDNs) have emerged as a promising alternative to these artificial drug delivery carriers for achieving safer clinical outcomes. In this study, we have generated CDNs from human adipose-derived stem cells (hASCs) using a high-yield fabrication strategy. Briefly, hASCs were subjected to a cell-shearing approach that entails passing the cells through an array of filters, along with serial centrifugations to eliminate intracellular contents. Ultimately, the fragmented parent cell membrane self-assembles to form the CDNs. This strategy successfully converted 80% of the plasma membrane into the novel nanocarriers with an average hydrodynamic diameter of 100 nm. Stability analysis confirmed that the formulated nanocarriers are stable for over 3 weeks, making them a potent candidate for long-term therapies. To demonstrate their potential in drug delivery, we encapsulated trehalose, a cell-impermeable sugar molecule, into the CDNs via an extrusion loading technique. Drug-loaded CDNs were effectively internalized into human umbilical vein endothelial cells (HUVECs) and hASCs, without inducing any significant cytotoxicity. Overall, the findings of this study establish the potential of hASC-derived CDNs as customizable biomimetic nanocarriers for drug delivery and other translational medicine applications.Over the years, the mechanism of copper homeostasis in various organ systems has gained importance. This is owing to the involvement of copper in a wide range of genetic disorders, most of them involving neurological symptoms. This highlights the importance of copper and its tight regulation in a complex organ system like the brain. It demands understanding the mechanism of copper acquisition and delivery to various cell types overcoming the limitation imposed by the blood brain barrier. The present review aims to investigate the existing work to understand the mechanism and complexity of cellular copper homeostasis in the two major cell types of the CNS - the neurons and the astrocytes. It investigates the mechanism of copper uptake, incorporation and export by these cell types. Furthermore, it brings forth the common as well as the exclusive aspects of neuronal and glial copper homeostasis including the studies from copper-based sensors. Glia act as a mediator of copper supply between the endothelium and the neurons.