A novel brain receptor is expressed in a distinct population of olfactory sensory neurons

Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor-expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules

The TNFR1 antagonist Atrosimab reduces neuronal loss, glial activation and memory deficits in an acute mouse model of neurodegeneration

Abstract Tumor necrosis factor alpha (TNF-α) and its key role in modulating immune responses has been widely recognized as a therapeutic target for inflammatory and neurodegenerative diseases. Even though inhibition of TNF-α is beneficial for the treatment of certain inflammatory diseases, total neutralization of TNF-α largely failed in the treatment of neurodegenerative diseases. TNF-α exerts distinct functions depending on interaction with its two TNF receptors, whereby TNF receptor 1 (TNFR1) is associated with neuroinflammation and apoptosis and TNF receptor 2 (TNFR2) with neuroprotection and immune regulation. Here, we investigated the effect of administering the TNFR1-specific antagonist Atrosimab, as strategy to block TNFR1 signaling while maintaining TNFR2 signaling unaltered, in an acute mouse model for neurodegeneration. In this model, a NMDA-induced lesion that mimics various hallmarks of neurodegenerative diseases, such as memory loss and cell death, was created in the nucleus basalis magnocellularis and Atrosimab or control protein was administered centrally. We showed that Atrosimab attenuated cognitive impairments and reduced neuroinflammation and neuronal cell death. Our results demonstrate that Atrosimab is effective in ameliorating disease symptoms in an acute neurodegenerative mouse model. Altogether, our study indicates that Atrosimab may be a promising candidate for the development of a therapeutic strategy for the treatment of neurodegenerative diseases

Influence of diamond crystal orientation on the interaction with biological matter

Diamond has been a popular material for a variety of biological applications due to its favorable chemical, optical, mechanical and biocompatible properties. While the lattice orientation of crystalline material is known to alter the interaction between solids and biological materials, the effect of diamond's crystal orientation on biological applications is completely unknown. Here, we experimentally evaluate the influence of the crystal orientation by investigating the interaction between the , and surfaces of the single crystal diamond with biomolecules, cell culture medium, mammalian cells and bacteria. We show that the crystal orientation significantly alters these biological interactions. Most surprising is the two orders of magnitude difference in the number of bacteria adhering on surface compared to surface when both the surfaces were maintained under the same condition. We also observe differences in how small biomolecules attach to the surfaces. Neurons or HeLa cells on the other hand do not have clear preferences for either of the surfaces. To explain the observed differences, we theoretically estimated the surface charge for these three low index diamond surfaces and followed by the surface composition analysis using x-ray photoelectron spectroscopy (XPS). We conclude that the differences in negative surface charge, atomic composition and functional groups of the different surface orientations lead to significant variations in how the single crystal diamond surface interacts with the studied biological entities. (c) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, butfew studies have reported on patient-reported outcomes (PROs) outside the context of a clinicaltrial. The goal of the current study was to assess PROs in participants of a lung cancer registry whohad been treated with an ICI. Patients participating in the GO2Foundation’s Lung Cancer Registrywho reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited toparticipate in a survey about their experiences during treatment. Quality of life was evaluated usingthe Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverseevents were evaluated using an item bank generated for ICIs. Internationally, 226 patients (meanage 61, 75% female) participated. Patients reported worse quality of life at the time of assessmentthan U.S. population and cancer normative samples. The most common moderate to severe adverseevents during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Dueto toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization.This study is among the first to our knowledge to report on PROs of ICIs outside the context of aclinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials

Targeting TNFR2 as a novel therapeutic strategy for Alzheimer's disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Accumulating experimental evidence shows the important linkage between tumor necrosis factor-α (TNF) and AD, but the exact role of TNF in AD is still not completely understood. Although TNF-inhibitors are successfully used for treating several diseases, total inhibition of TNF can cause side effects, particularly in neurological diseases. This is attributed to the opposing roles of the two TNF receptors. TNF receptor 1 (TNFR1) predominantly mediates inflammatory and pro-apoptotic signaling pathways, whereas TNF receptor 2 (TNFR2) is neuroprotective and promotes tissue regeneration. Therefore, the specific activation of TNFR2 signaling, either by directly targeting TNFR2 via TNFR2 agonists or by blocking TNFR1 signaling with TNFR1-selective antagonists, seems a promising strategy for AD therapy. This mini-review discusses the involvement of TNFR2 and its signaling pathway in AD and outlines its potential application as therapeutic target. A better understanding of the function of TNFR2 may lead to the development of a treatment for AD

Distinct immune responses in people living with HIV following SARS-CoV-2 recovery

Background SARS-CoV-2 infection results in greater disease severity among immunocompromised individuals compared to healthy individuals. However, there is conflicting information about the impact of chronic HIV infection on immune responses to SARS-CoV-2 infection and vaccination. Method We used a combination of machine learning approaches and network analysis to explore 56 immune markers and comprehensively profile humoral and cellular immunity in a cross-sectional observational cohort of people without HIV (PWOH; n = 216) and people living with HIV (PLWH; n = 43) who recovered from SARS-CoV-2 infection (13–131 days since SARS-COV-2 diagnosis) early in the pandemic. Results PLWH recovered from symptomatic outpatient COVID-19 exhibit lower humoral and B cell responses to SARS-CoV-2 vs. PWOH but, surprisingly, both symptomatic outpatient and hospitalized PLWH have higher anti-endemic coronavirus antibody responses compared to PWOH counterparts and asymptomatic PLWH. The latter observation suggests that this was not strictly due to broadly elevated levels of anti-endemic coronavirus antibodies in PLWH. Moreover, correlation-based analysis reveals that while different compartments of the immune response to SARS-CoV-2 infection are positively correlated in PWOH recovered from symptomatic outpatient COVID-19, these correlations are weaker in PLWH. Conclusion Our analyses reveal significant differences in the coordinated immune responses elicited by infection in PLWH compared to PWOH