Bridging the gap between presynaptic hair cell function and neural sound encoding.

Neural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca channels.

Development of a novel tool for individual treatment trials in mucopolysaccharidosis.

Mucopolysaccharidosis (MPS) encompasses a group of genetic lysosomal storage disorders, linked to reduced life expectancy and a significant lack of effective treatment options. Immunomodulatory drugs could have the potential to be a relevant medical approach, as the accumulation of undegraded substances initiates an innate immune response, which leads to inflammation and clinical deterioration. However, immunomodulators are not licensed for this indication.

Impact of Continuous Ofatumumab Exposure During Pregnancy in Multiple Sclerosis.

Objectives: Anti-CD20 therapies are highly effective treatment options for patients with multiple sclerosis (MS), an inflammatory disorder of the CNS commonly affecting women of childbearing age. Anti-CD20 therapies are however unlicensed for use in pregnancy. Belonging to the IgG1 family, anti-CD20 monoclonal antibodies are likely to cross the placenta, especially after the 20th week of gestation.

Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.

Background: Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences.

Cryo-EM Structure of the Mnx Protein Complex Reveals a Tunnel Framework for the Mechanism of Manganese Biomineralization.

The global manganese cycle relies on microbes to oxidize soluble Mn(II) to insoluble Mn(IV) oxides. Some microbes require peroxide or superoxide as oxidants, but others can use O directly, via multicopper oxidase (MCO) enzymes. One of these, MnxG from strain PL-12, was isolated in tight association with small accessory proteins, MnxE and MnxF.

Dysferlin Enables Tubular Membrane Proliferation in Cardiac Hypertrophy.

Background: Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies but can result in heart failure if left untreated. Here, we hypothesized that the membrane fusion and repair protein dysferlin is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes and contributes to the proliferation of TAT endomembranes during pressure overload-induced cardiac hypertrophy.

Methods: Stimulated emission depletion and electron microscopy were used to localize dysferlin in mouse and human cardiomyocytes.

Clinical Application of ISO and CEN/TS Standards for Liquid Biopsies-Information Everybody Wants but Nobody Wants to Pay For.

Background: Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Although International Organization for Standards (ISO) and Technical Specifications from the European Committee for Standardization (CEN/TS) standardized workflows exist, their implementation in clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS standards in a real-world clinical setting, with a particular focus on evaluating the impact of preanalytical parameters and hemolysis on liquid biopsy analysis.

Alemtuzumab treatment for multiple sclerosis in Austria: An observational long-term outcome study.

Background/objective: Observational real-world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease-modifying therapy (DMT) usage in multiple sclerosis (MS).

Methods: Data retrieved from the Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6-month confirmed progression independent of relapse activity (PIRA; ≥ 0.5-point Expanded Disability Status Scale (EDSS) score increase), 6-month confirmed disability improvement (CDI; ≥ 0.

Highly Active WC-Based Composites for the HER in Alkaline Solution: the Role of Surface Oxide Species.

The hydrogen evolution reaction (HER) is a crucial electrochemical process for the proposed hydrogen economy since it has the potential to provide pure hydrogen for fuel cells. Nowadays, hydrogen electroproduction is considerably expensive, so promoting the development of new non-noble catalysts for the cathode of alkaline electrolyzers appears as a suitable way to reduce the costs of this technology. In this sense, a series of tungsten-based carbide materials have been synthesized by the urea-glass route as candidates to improve the HER in alkaline media.

Fabrication and Characterization of PDMS Waveguides for Flexible Optrodes.

With the growth of optogenetic research, the demand for optical probes tailored to specific applications is ever rising. Specifically, for applications like the coiled cochlea of the inner ear, where planar, stiff, and nonconformable probes can hardly be used, transitioning from commonly used stiff glass fibers to flexible probes is required, especially for long-term use. Following this demand, polydimethylsiloxane (PDMS) with its lower Young's modulus compared to glass fibers can serve as material of choice.

Toward Optogenetic Hearing Restoration.

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs.

Beyond T cell toxicity - Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: A two-case series and literature review.

Background And Purpose: This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).

Methods: A systematic literature review was made, with case observations of a melanoma and a non-small cell lung cancer (NSCLC) patient who developed ICI-associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.

Results: Two patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c-LETM), respectively.

Optical measurement of glutamate release robustly reports short-term plasticity at a fast central synapse.

Introduction: Recently developed fluorescent neurotransmitter indicators have enabled direct measurements of neurotransmitter in the synaptic cleft. Precise optical measurements of neurotransmitter release may be used to make inferences about presynaptic function independent of electrophysiological measurements.

Methods: Here, we express iGluSnFR, a genetically encoded glutamate reporter in mouse spiral ganglion neurons to compare electrophysiological and optical readouts of presynaptic function and short-term synaptic plasticity at the endbulb of Held synapse.

Surpassing sensitivity limits in liquid biopsy.

Attenuation of cell-free DNA clearance in vivo is an alternative strategy to maximize recovery.

Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.

Objective: Repeated intravenous administration of anti-CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions in people with MS (pwMS).

Methods: We studied pwMS treated de-novo with either RTX (n = 7) or OCR (n = 8).

Proteomic Analysis Reveals the Composition of Glutamatergic Organelles of Auditory Inner Hair Cells.

In the ear, inner hair cells (IHCs) employ sophisticated glutamatergic ribbon synapses with afferent neurons to transmit auditory information to the brain. The presynaptic machinery responsible for neurotransmitter release in IHC synapses includes proteins such as the multi-C-domain protein otoferlin and the vesicular glutamate transporter 3 (VGluT3). Yet, much of this likely unique molecular machinery remains to be deciphered.

Multichannel laser diode to polymer waveguide array coupling with a double-aspheric lens.

An optical system for multichannel coupling of laser arrays to polymer waveguide array probes with a single biconvex lens is developed. The developed cylindrical module with 13 mm and 20 mm in diameter and length, respectively, enables coupling of eight individual optical channels using an aspheric lens. Specific coupling with crosstalk below -13 for each channel and quasi-uniform coupling over all channels is achieved for a waveguide array with 100 µm lateral facet pitch at the incoupling site.