Antigen-specific age-related memory CD8 T cells induce and track Alzheimer's-like neurodegeneration.

Cerebral (Aβ) plaque and (pTau) tangle deposition are hallmarks of Alzheimer's disease (AD), yet are insufficient to confer complete AD-like neurodegeneration experimentally. Factors acting upstream of Aβ/pTau in AD remain unknown, but their identification could enable earlier diagnosis and more effective treatments. T cell abnormalities are emerging AD hallmarks, and CD8 T cells were recently found to mediate neurodegeneration downstream of tangle deposition in hereditary neurodegeneration models.

Amyloid-α Peptide Formed through Alternative Processing of the Amyloid Precursor Protein Attenuates Alzheimer's Amyloid-β Toxicity via Cross-Chaperoning.

Amyloid aggregation is a key feature of Alzheimer's disease (AD) and a primary target for past and present therapeutic efforts. Recent research is making it increasingly clear that the heterogeneity of amyloid deposits, extending past the commonly targeted amyloid-β (Aβ), must be considered for successful therapy. We recently demonstrated that amyloid-α (Aα or p3), a C-terminal peptidic fragment of Aβ, aggregates rapidly to form amyloids and can expedite the aggregation of Aβ through seeding.

Team science: A syllabus for success on big projects.

Interdisciplinary teams are on the rise as scientists attempt to address complex environmental issues. While the benefits of team science approaches are clear, researchers often struggle with its implementation, particularly for new team members. The challenges of large projects often weigh on the most vulnerable members of a team: trainees, including undergraduate students, graduate students, and post-doctoral researchers.

Evolutionary Selection of APOEɛ4 Encourages Increased Focus on Immunity in Alzheimer's Disease.

Smith and Ashford present a compelling hypothesis on evolution of APOE alleles, namely that ɛ4 prevalence is mediated by immune selection pressure against enteric pathogens. While the ɛ3 allele is more prevalent today, it outcompetedɛ4 only relatively recently, as immune selection pressure for more effective immune responses to such pathogens was alleviated with transition to agrarian from hunter-gatherer lifestyles. Smith and Ashford's hypothesis is intriguing in itself, but the implications for APOE ɛ4 function in Alzheimer's disease are even more so and encourage greater focus on specific aspects of immunity in accounting for both ɛ4-mediated and general Alzheimer's disease risk.

Glioma immunotherapy enhancement and CD8-specific sialic acid cleavage by isocitrate dehydrogenase (IDH)-1.

The promise of adaptive cancer immunotherapy in treating highly malignant tumors such as glioblastoma multiforme (GBM) can only be realized through expanding its benefits to more patients. Alleviating various modes of immune suppression has so far failed to achieve such expansion, but exploiting endogenous immune enhancers among mutated cancer genes could represent a more direct approach to immunotherapy improvement. We found that Isocitrate Dehydrogenase-1 (IDH1), which is commonly mutated in gliomas, enhances glioma vaccine efficacy in mice and discerns long from short survivors after vaccine therapy in GBM patients.

Performance of cough monitoring by Albus Home, a contactless and automated system for nocturnal respiratory monitoring at home.

Introduction: Objective cough frequency is a key clinical end-point but existing wearable monitors are limited to 24-h recordings. Albus Home uses contactless motion, acoustic and environmental sensors to monitor multiple metrics, including respiratory rate and cough without encroaching on patient lifestyle. The aim of this study was to evaluate measurement characteristics of nocturnal cough monitoring by Albus Home compared to manual counts.

Performance of Contactless Respiratory Rate Monitoring by Albus Home, an Automated System for Nocturnal Monitoring at Home: A Validation Study.

Respiratory rate (RR) is a clinically important predictor of cardio-respiratory deteriorations. The mainstay of clinical measurement comprises the manual counting of chest movements, which is variable between clinicians and limited to sporadic readings. Emerging solutions are limited by poor adherence and acceptability or are not clinically validated.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide.

CD103 Deficiency Promotes Autism (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) Behavioral Spectra and Reduces Age-Related Cognitive Decline.

The incidence of autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), which frequently co-occur, are both rising. The causes of ASD and ADHD remain elusive, even as both appear to involve perturbation of the gut-brain-immune axis. CD103 is an integrin and E-cadherin receptor most prominently expressed on CD8 T cells that reside in gut, brain, and other tissues.

COVID-19: Review of a 21st Century Pandemic from Etiology to Neuro-psychiatric Implications.

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large.

Functional recreation of age-related CD8 T cells in young mice identifies drivers of aging- and human-specific tissue pathology.

Mitigating effects of aging on human health remains elusive because aging impacts multiple systems simultaneously, and because experimental animals exhibit critical aging differences relative to humans. Separation of aging into discrete processes may identify targetable drivers of pathology, particularly when applied to human-specific features. Gradual homeostatic expansion of CD8 T cells dominantly alters their function in aging humans but not in mice.

A phase I trial of surgical resection with Gliadel Wafer placement followed by vaccination with dendritic cells pulsed with tumor lysate for patients with malignant glioma.

High grade gliomas are associated with poor prognosis and high mortality. Conventional treatments and management of high grade gliomas have shown little improvement in 5-year overall survival. This phase I trial evaluated the safety, immunogenicity, and potential synergy of surgical resection with Gliadel Wafer implantation, followed by autologous tumor lysate-pulsed dendritic cell (DC) vaccine in patients with malignant glioma.

A Simple Three-dimensional Hydrogel Platform Enables Cell Culture of Patient and PDX Tumors for Assaying Their Response to Clinically Relevant Therapies.

A cell culture platform that enables tissue growth from patients or patient-derived xenograft (PDX) models and assesses sensitivity to approved therapies (e.g., temozolomide) in a clinically relevant time frame would be very useful in translational research and personalized medicine.

Using a Concept Inventory to Assess the Reasoning Component of Citizen-Level Science Literacy: Results from a 17,000-Student Study.

After articulating 12 concepts for the reasoning component of citizen-level science literacy and restating these as assessable student learning outcomes (SLOs), we developed a valid and reliable assessment instrument for addressing the outcomes with a brief 25-item science literacy concept inventory (SLCI). In this paper, we report the results that we obtained from assessing the citizen-level science literacy of 17,382 undergraduate students, 149 graduate students, and 181 professors. We address only findings at or above the 99.

Human Hematopoietic Signal peptide-containing Secreted 1 (hHSS1) modulates genes and pathways in glioma: implications for the regulation of tumorigenicity and angiogenesis.

Background: Human Hematopoietic Signal peptide-containing Secreted 1 (hHSS1) is a truly novel protein, defining a new class of secreted factors. We have previously reported that ectopic overexpression of hHSS1 has a negative modulatory effect on cell proliferation and tumorigenesis in glioblastoma model systems. Here we have used microarray analysis, screened glioblastoma samples in The Cancer Genome Atlas (TCGA), and studied the effects of hHSS1 on glioma-derived cells and endothelial cells to elucidate the molecular mechanisms underlying the anti-tumorigenic effects of hHSS1.

T-Lymphocyte Deficiency Exacerbates Behavioral Deficits in the 6-OHDA Unilateral Lesion Rat Model for Parkinson's Disease.

T-lymphocytes have been previously implicated in protecting dopaminergic neurons in the substantianigra from induced cell death. However, the role of T-cells in neurodegenerative models such as Parkinson's disease (PD) has not been fully elucidated. To examine the role of T-lymphocytes on motor behavior in the 6-hydroxydopamine (6-OHDA) unilateral striatal partial lesion PD rat model, we assessed progression of hemi-parkinsonian lesions in the substantia nigra, induced by 6-OHDA striatal injections, in athymic rats (RNU-/-, T-lymphocyte-deficient) as compared to RNU-/+ rats (phenotypically normal).

Intrinsically de-sialylated CD103(+) CD8 T cells mediate beneficial anti-glioma immune responses.

Background: Cancer vaccines reproducibly cure laboratory animals and reveal encouraging trends in brain tumor (glioma) patients. Identifying parameters governing beneficial vaccine-induced responses may lead to the improvement of glioma immunotherapies. CD103(+) CD8 T cells dominate post-vaccine responses in human glioma patients for unknown reasons, but may be related to recent thymic emigrant (RTE) status.

Following in their footprints: cuticular hydrocarbons as overwintering aggregation site markers in Hippodamia convergens.

The convergent lady beetle (Hippodamia convergens) forms large overwintering aggregations at revisited montane microsites far removed from their summer foraging grounds. Although orientation responses to visual and altitudinal features of habitat can explain the arrival of migrants at the general overwintering macrosite, the role that pheromones play in the accumulation of individuals in inconspicuous hibernacula microsites is not fully understood. Through two-choice bioassays and gas chromatography and mass spectrometry, we found that H.

Exploitation of adaptive evolution in glioma treatment.

Glioblastoma multiforme (GBM) is a malignant neoplasm of the CNS with almost uniform lethality. Even with standard-of-care treatments, the prognosis for patients remains dismal. GBM, as with other malignancies, often acquires treatment resistance after an initial response to therapy.

Defensive allomones function as aggregation pheromones in diapausing Ladybird Beetles, Hippodamia convergens.

Identification of the stimuli responsible for the formation of an aggregation can be used to distinguish between social and non-social aggregations and help in the process of identifying the adaptive benefits of the gregarious behavior. The convergent ladybird beetle, Hippodamia convergens, forms dense aggregations during winter diapause. The mechanisms of conspecific attraction and hibernacula site selection of H.

Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.

The molecular mechanism underlying tumor-induced epileptogenesis is poorly understood. Alterations in the peritumoral microenvironment are believed to play a significant role in inducing epileptogenesis. We hypothesize that the change of gene expression in brain peritumoral tissues may contribute to the increased neuronal excitability and epileptogenesis.

Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma.

Background: This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107).

Methods: TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible.

Vaccines for glioblastoma and high-grade glioma.

Vaccination by administering tumor antigen plus cell-free or cellular adjuvant has garnered hope for more effective, less toxic therapy for patients with malignant brain tumors including glioblastoma multiforme. To determine if this approach demonstrates ample clinical promise, all published reports of vaccination for glioma were evaluated. These reports suggest vaccination is associated with low toxicity and favorable clinical outcomes.