Complementary techniques for the reliable characterisation of tissue samples: A case study on pancreatic tumours analysed by means of X-ray fluorescence analysis and IR spectroscopy.

An improvement in the reliability and comparability of tissue characterization results is crucial for enabling further progress in cancer detection and the assessment of therapeutic effects. This can only be achieved by integrating quantitative methods into well-established qualitative characterization routines. This case study presents a hybrid metrological approach for tissue characterisation including vibrational Fourier Transform InfraRed (FTIR) spectroscopy and traceable reference-free X-Ray Fluorescence analysis (XRF).

PROJECT DiViNe: DIVERSE VOICES IN NEUROSCIENCE: Profiles of Rita Levi-Montalcini, Ricardo Miledi, Simon LeVay, Erich Jarvis, and Steve Ramirez.

In this paper we share the first five of what we hope will be many profiles of neuroscientists from historically underrepresented or marginalized groups. This initial collection of profiles, meant to stake out the general territory for future offerings, takes as its subjects a fairly broad range of individuals from Nobel laureates to early career scientists and educators. The goal of this project is to facilitate the dissemination of materials neuroscience educators can use to highlight the scientific contributions and personal stories of scientists from historically marginalized groups, and has been developed more extensively in the Editorial that accompanies this collection (Frenzel and Harrington, 2021).

Celebrating Diverse Voices in Neuroscience: Introducing Project DiViNe.

Institutions of higher education are meant to provide opportunities for the growth and development of their students. As student bodies have become more diverse it would seem to follow that institutional efforts to satisfy this obligation would likewise need to change. Despite increases in the numbers of historically underrepresented students entering higher education, the proportion of these students who graduate continues to lag behind that of students who are not historically underrepresented.

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Further, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities.

Actively personalized vaccination trial for newly diagnosed glioblastoma.

Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential. There is limited intratumoural infiltration of immune cells in glioblastoma and these tumours contain only 30-50 non-synonymous mutations.

Identification of Tumor Antigens Among the HLA Peptidomes of Glioblastoma Tumors and Plasma.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities.

Epilepsy and the Action Potential: Using Case Based Instruction and Primary Literature in a Neurobiology Course.

Epilepsy and seizure generation are at the center of this case study narrative. By exploring the nature of genetic mutations in voltage-gated sodium channels students will solidify fundamental concepts involving action potential generation and roles for excitatory and inhibitory neurons in the central nervous system. Students will wrestle with primary data, developing analytical and quantitative skills, and generate evidence-based hypotheses and predictions.

From Botox to Behavior: Neuroscience for Non-Scientists at Emory.

For the past six years, we have been teaching a neuroscience for non-science majors course titled "From Botox to Behavior: Neuroscience for non-scientists." The primary objectives for this course are to create science literate students using neuroscience concepts as the foundation. The evidence from our course assessments suggest that the students are learning fundamental concepts and developing skills of source evalution, using evidence in an argument and appreciating the role of neuroscience in society.

The multi-target effects of CNI-1493: convergence of anti-amylodogenic and anti-inflammatory properties in animal models of Alzheimer's disease.

After several decades of Alzheimer's disease (AD) research and failed clinical trials, one can speculate that targeting a single pathway is not sufficient. However, a cocktail of novel therapeutics will constitute a challenging clinical trial. A more plausible approach will capitalize on a drug that has relevant and synergistic multiple-target effects in AD.

Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity.

Defects of the intracellular enzyme 3' repair exonuclease 1 (Trex1) cause the rare autoimmune condition Aicardi-Goutières syndrome and are associated with systemic lupus erythematosus. Trex1(-/-) mice develop type I IFN-driven autoimmunity, resulting from activation of the cytoplasmic DNA sensor cyclic GMP-AMP synthase by a nucleic acid substrate of Trex1 that remains unknown. To identify cell types responsible for initiation of autoimmunity, we generated conditional Trex1 knockout mice.

Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation.

Recent studies have shown that tissue macrophages (MΦ) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize tissues before birth. Further studies have proposed that developmentally distinct tissue MΦ can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we took advantage of an inducible fate-mapping system that facilitated the identification of CD45(+)c-kit(-)CX3CR1(+)F4/80(+) (A2) progenitors of the YS as the source of F4/80(hi) but not CD11b(hi) MΦ.

Nora's Medulla: A Problem-Based Learning Case for Neuroscience Fundamentals.

Students work through this Problem-Based Learning Case in order to discover how Nora ended up blue lipped and non-responsive. By exploring fundamental mechanisms of neuronal communication, students examine facts, research concepts, and propose hypotheses about how Nora's physiology was disrupted to cause her respiratory distress. The dramatic context supports student learning at many levels - from systems neurophysiology to synaptic pharmacology.

Origin, fate and dynamics of macrophages at central nervous system interfaces.

Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes.

Moraxella catarrhalis decreases antiviral innate immune responses by down-regulation of TLR3 via inhibition of p53 in human bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) is complicated by infectious exacerbations with acute worsening of respiratory symptoms. Coinfections of bacterial and viral pathogens are associated with more severe exacerbations. Moraxella catarrhalis is one of the most frequent lower respiratory tract pathogens detected in COPD.

Identification of two metallothioneins as novel inhalative coffee allergens cof a 2 and cof a 3.

Background: Dust of green coffee beans is known to be a relevant cause for occupational allergic disorders in coffee industry workers. Recently, we described the first coffee allergen (Cof a 1) establishing an allergenic potential of green coffee dust.

Objective: Our aim was to identify allergenic components of green coffee in order to enhance inhalative coffee allergy diagnosis.

USP18 lack in microglia causes destructive interferonopathy of the mouse brain.

Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called "microgliopathies". However, how the intracellular stimulation machinery in microglia is controlled is poorly understood.

Progressive replacement of embryo-derived cardiac macrophages with age.

Cardiac macrophages (cMΦ) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1(+) cMΦ diversifies into MHCII(+) and MHCII(-) cells.

Combination of immunoglobulins and natural killer cells in the context of CMV and EBV infection.

Cytomegalovirus (CMV)-specific hyperimmunoglobulin (CMV-HIG) is used to treat and prevent CMV infection in immunocompromised patients, and anti-CD20 monoclonal antibody is successfully used in the treatment for post-transplant lymphoproliferative disease caused by Epstein-Barr virus (EBV). Two immunological approaches have been suggested to further improve the control of viral reproduction in patients with active disease: first, the use of monoclonal antibodies with specificity against viral epitopes and second, coadministration of cells with the capacity to promote antibody-dependent cell-mediated cytotoxicity. Here, we have evaluated the effectiveness of these strategies in vitro (alone and in combination) with neutralization and cytotoxicity assays.

Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor γ.

During central nervous system autoimmunity, interactions between infiltrating immune cells and brain-resident cells are critical for disease progression and ultimately organ damage. Here, we demonstrate that local cross-talk between invading autoreactive T cells and auto-antigen-presenting myeloid cells within the central nervous system results in myeloid cell activation, which is crucial for disease progression during experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. This T cell-mediated licensing of central nervous system myeloid cells triggered astrocytic CCL2-release and promoted recruitment of inflammatory CCR2(+)-monocytes, which are the main effectors of disease progression.

Antiviral function and efficacy of polyvalent immunoglobulin products against CMV isolates in different human cell lines.

Primary infection and reactivation of human cytomegalovirus (CMV) remain a major problem in immunocompromised patients, frequently resulting in a life threatening CMV disease. Intravenous polyvalent (hyper)-immunoglobulins (IVIG) can be administered for therapy and prophylaxis of CMV infections. However, only limited data about the efficacy and mechanism of action of IVIG products against viral infections in vitro are available so far.

Intrathecal EBV antibodies are part of the polyspecific immune response in multiple sclerosis.

Objective: One mechanism underlying the link between multiple sclerosis (MS) and Epstein-Barr virus (EBV) might be a direct CNS infection. Viral CNS infections cause elevated antibody indices (AIs). Elevated EBV AIs were found in MS; however, patients with MS frequently show a polyspecific intrathecal immune response with elevated antiviral AIs.