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Development and validation of a novel Simoa assay for NPTX2 in Alzheimer's disease and Down syndrome

INTRODUCTION: Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders. METHODS: We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, w

Immunity to the microbiota promotes sensory neuron regeneration

Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with

Mesenchymal stromal cell-derived nanovesicles ameliorate bacterial outer membrane vesicle-induced sepsis via IL-10

BACKGROUND: Sepsis remains a source of high mortality in hospitalized patients despite proper antibiotic approaches. Encouragingly, mesenchymal stromal cells (MSCs) and their produced extracellular vesicles (EVs) have been shown to elicit anti-inflammatory effects in multiple inflammatory conditions including sepsis. However, EVs are generally released from mammalian cells in relatively low amount

The CTA1-DD adjuvant strongly potentiates follicular dendritic cell function and germinal center formation, which results in improved neonatal immunization

Vaccination of neonates and young infants is hampered by the relative immaturity of their immune systems and the lack of safe and efficacious vaccine adjuvants. Immaturity of the follicular dendritic cells (FDCs), in particular, appears to play a critical role for the inability to stimulate immune responses. Using the CD21mT/mG mouse model we found that at 7 days of life, FDCs exhibited a mature p

Optimizing energy usage and reducing waste Digital Twin applications in industrial IoT

Industrial sector, by boosting energy efficiency and reducing waste through the use of digital twin (DT) technology in the integration of industrial IoT (IIoT). DT generates realistic simulations for predictive analytics and decision-making with the help of real-time simulations of physical objects. In this chapter, the authors focus on the DT application for the optimum utilization of energy and

Skin autonomous antibody production regulates host-microbiota interactions

The microbiota colonizes each barrier site and broadly controls host physiology1. However, when uncontrolled, microbial colonists can also promote inflammation and induce systemic infection2. The unique strategies used at each barrier tissue to control the coexistence of the host with its microbiota remain largely elusive. Here we uncover that, in the skin, host-microbiota symbiosis depends on the

Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy

Bacterial outer membrane vesicles (OMV) have gained attention as a promising new cancer vaccine platform for efficiently provoking immune responses. However, OMV induce severe toxicity by activating the innate immune system. In this study, we applied a simple isolation approach to produce artificial OMV that we have named Synthetic Bacterial Vesicles (SyBV) that do not induce a severe toxic respon

Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reductio

Diagnostic performance of plasma Aβ42/40 ratio, p-tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non-AD dementias : An international multi-center study

INTRODUCTION: Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study. METHODS: Plasma samples (n = 1298) w

Optimization of MoRe contacts to InGaAs Quantum Wells

This thesis presents the design, fabrication, and characterization of molybdenum–rhenium (MoRe) based MOSFET on InAlAs and InGaAs heterostructures, aiming to integrate superconducting contacts with III–V semiconductors for hybrid quantum compatible devices. The study addresses interfacial challenges that limit contact transparency and investigates different surface preparation and passivation tech

Discovery and engineering of the antibody response to a prominent skin commensal

The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection1. However, the scope and purpose of this anticommensal immune programme are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable and specific antibody response that is conserved in human

A vaccine combination of lipid nanoparticles and a cholera toxin adjuvant derivative greatly improves lung protection against influenza virus infection

This is a proof-of-principle study demonstrating that the combination of a cholera toxin derived adjuvant, CTA1-DD, and lipid nanoparticles (LNP) can significantly improve the immunogenicity and protective capacity of an intranasal vaccine. We explored the self-adjuvanted universal influenza vaccine candidate, CTA1-3M2e-DD (FPM2e), linked to LNPs. We found that the combined vector greatly enhanced

Therapeutic impact of leuprorelin acetate on spinal and bulbar muscular atrophy : pre- and post-marketing observational study

Although leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, has been approved based on short-term clinical trials conducted in Japan, its long-term efficacy on physical function remains unclear. We aimed to evaluate the long-term therapeutic efficacy of leuprorelin acetate using real-world clinical data through a self-controlled trend-shift analysis. The analysis included 91 gen

Cross-Protective Potential and Protection-Relevant Immune Mechanisms of Whole Inactivated Influenza Virus Vaccines Are Determined by Adjuvants and Route of Immunization

Adjuvanted whole inactivated virus (WIV) influenza vaccines show promise as broadly protective influenza vaccine candidates. Using WIV as basis we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the liposome-based adjuvants CAF01 and CAF09 and the protein-based adjuvants CTA1-DD and CTA1-3M2e-DD and evaluated whether one or more of the adjuvants c

Home-based Hybrid Assistive Limb Lumbar Type Telerehabilitation in Spinocerebellar Ataxias : A Nonrandomized Open-label Trial

A hybrid assistive limb (HAL) can improve the motor performance of patients with various neurodegenerative diseases, but the efficacy of home-based rehabilitation using HAL for spinocerebellar ataxias (SCA) has yet to be elucidated. To evaluate the efficacy and safety of home-based telerehabilitation with lumbar type HAL in patients with SCA. In this non-randomized open-label single center trial,