Molecular Evidence for Altered Angiogenesis in Neuroinflammation-Associated Schizophrenia and Bipolar Disorder Implicate an Abnormal Midbrain Blood-Brain Barrier.

Background And Hypothesis: Angiogenesis triggered by inflammation increases BBB permeability and facilitates macrophage transmigration. In the midbrain, we have discovered molecular alterations related to the blood-brain barrier (BBB), including endothelial cell changes associated with macrophage diapedesis, in neuroinflammatory schizophrenia and bipolar disorder, but changes in angiogenesis are yet to be reported. Hypothesis: We expected to discover molecular evidence of altered angiogenesis in the midbrain in individuals with schizophrenia and bipolar disorder compared to controls, with these changes more evident in "high" inflammation schizophrenia as compared to "low" inflammation.

Increased Parenchymal Macrophages are associated with decreased Tyrosine Hydroxylase mRNA levels in the Substantia Nigra of people with Schizophrenia and Bipolar Disorder.

Increased activation of inflammatory macrophages and altered expression of dopamine markers are found in the midbrains of people with schizophrenia (SZ). The relationship of midbrain macrophages to dopamine neurons has not been explored, nor is it known if changes in midbrain macrophages are also present in bipolar disorder (BD) or major depressive disorder (MDD). Herein, we determined whether there were differences in CD163+ cell density in the Substantia Nigra (SN), and cerebral peduncles (CP) of SZ, BD, and MDD compared to controls (CTRL).

Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation.

Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4A exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4 and CD3CD4CD8 double-negative T cells over CD8 T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice.

Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants.

Genes mutated in monogenic neurodevelopmental disorders are broadly expressed. This observation supports the concept that monogenic neurodevelopmental disorders are systemic diseases that profoundly impact neurodevelopment. We tested the systemic disease model focusing on Rett syndrome, which is caused by mutations in MECP2.

Quantification and persistence of COVID-19 virus in recently deceased individuals before and after embalming.

The COVID-19 pandemic severely affected the medical education worldwide. The infection risk for medical students and healthcare personnel who work with COVID-19 positive cadavers or tissues remains unclear. Moreover, COVID-19 positive cadavers have been rejected by medical schools, adversely impacting the continuum of medical education.

Systemic Proteome Phenotypes Reveal Defective Metabolic Flexibility in Mecp2 Mutants.

Genes mutated in monogenic neurodevelopmental disorders are broadly expressed. This observation supports the concept that monogenic neurodevelopmental disorders are systemic diseases that profoundly impact neurodevelopment. We tested the systemic disease model focusing on Rett syndrome, which is caused by mutations in MECP2.

Increased prefrontal cortical cells positive for macrophage/microglial marker CD163 along blood vessels characterizes a neuropathology of neuroinflammatory schizophrenia.

Transcript levels of cytokines and SERPINA3 have been used to define a substantial subset (40%) of individuals with schizophrenia with elevated inflammation and worse neuropathology in the dorsolateral prefrontal cortex (DLPFC). In this study, we tested if inflammatory proteins are likewise related to high and low inflammatory states in the human DLFPC in people with schizophrenia and controls. Levels of inflammatory cytokines (IL6, IL1β, IL18, IL8) and a macrophage marker (CD163 protein) were measured in brains obtained from the National Institute of Mental Health (NIMH) (N = 92).

Changes in cytokine and cytokine receptor levels during postnatal development of the human dorsolateral prefrontal cortex.

In addition to their traditional roles in immune cell communication, cytokines regulate brain development. Cytokines are known to influence neural cell generation, differentiation, maturation, and survival. However, most work on the role of cytokines in brain development investigates rodents or focuses on prenatal events.

Clinical Features of Genetic Resilience in Chronic Obstructive Pulmonary Disease.

Introduction: In the personalized risk quantification of chronic obstructive pulmonary disease (COPD), genome-wide association studies and polygenic risk scores (PRS) complement traditional risk factors, such as age and cigarette smoking. However, despite being at considerable levels of risk, some individuals do not develop COPD. Research on COPD resilience remains largely unexplored.

Coupling freedom from disease principles and early warning from wastewater surveillance to improve health security.

Infectious disease surveillance is vitally important to maintaining health security, but these efforts are challenged by the pace at which new pathogens emerge. Wastewater surveillance can rapidly obtain population-level estimates of disease transmission, and we leverage freedom from disease principles to make use of nondetection of SARS-CoV-2 in wastewater to estimate the probability that a community is free from SARS-CoV-2 transmission. From wastewater surveillance of 24 treatment plants across upstate New York from May through December of 2020, trends in the intensity of SARS-CoV-2 in wastewater correlate with trends in COVID-19 incidence and test positivity ( > 0.

The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited therapeutic options. The extracellular matrix protein fibulin-3/EFEMP1 accumulates in the pleural effusions of MPM patients and has been proposed as a prognostic biomarker of these tumors. However, it is entirely unknown whether fibulin-3 plays a functional role on MPM growth and progression.

Infection with Increases the Replication and Dissemination of Coinfecting Powassan Virus in Ticks.

Powassan virus (POWV) is a tick-borne neuroinvasive flavivirus endemic to North America. It is generally transmitted by the tick, . This species also transmits , the causative agent of Lyme disease.

Distinct Phenotypes of Inflammation Associated Macrophages and Microglia in the Prefrontal Cortex Schizophrenia Compared to Controls.

Approximately 40% of people with schizophrenia are classified as having "high inflammation." This subgroup has worse neuropathology than patients with "low inflammation." Thus, one would expect the resident microglia and possibly monocyte-derived macrophages infiltrating from the periphery to be "activated" in those with schizophrenia with elevated neuroinflammation.

Inflammation-related transcripts define "high" and "low" subgroups of individuals with schizophrenia and bipolar disorder in the midbrain.

Dopamine dysregulation in schizophrenia may be associated with midbrain inflammation. Previously, we found elevated levels of pro-inflammatory cytokine mRNAs in the post-mortem midbrain of people with schizophrenia (46%) but not from unaffected controls (0%) using a brain cohort from Sydney, Australia. Here, we measured cytokine mRNAs and proteins in the midbrain in the Stanley Medical Research Institute (SMRI) array cohort (N = 105).

High Sensitivity and Specificity of Dormitory-Level Wastewater Surveillance for COVID-19 during Fall Semester 2020 at Syracuse University, New York.

A residential building's wastewater presents a potential non-invasive method of surveilling numerous infectious diseases, including SARS-CoV-2. We analyzed wastewater from 16 different residential locations at Syracuse University (Syracuse, NY, USA) during fall semester 2020, testing for SARS-CoV-2 RNA twice weekly and compared the presence of clinical COVID-19 cases to detection of the viral RNA in wastewater. The sensitivity of wastewater surveillance to correctly identify dormitories with a case of COVID-19 ranged from 95% (95% confidence interval [CI] = 76-100%) on the same day as the case was diagnosed to 73% (95% CI = 53-92%), with 7 days lead time of wastewater.

Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance.

Development and Validation of Two RT-qPCR Diagnostic Assays for Detecting Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Targets across Two Specimen Types.

Following the outbreak and subsequent pandemic of coronavirus disease 2019 (COVID-19), clinical diagnostic laboratories worldwide sought accurate and reliable testing methodologies. However, many laboratories were and still are hindered by a number of factors, including an unprecedented demand for testing, reagent and laboratory supply shortages and availability of qualified staff. To respond to these concerns, two separate laboratory-developed tests were validated for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using two different specimen types.

Cytosolic adaptation to mitochondria-induced proteostatic stress causes progressive muscle wasting.

Mitochondrial dysfunction causes muscle wasting in many diseases and probably also during aging. The underlying mechanism is poorly understood. We generated transgenic mice with unbalanced mitochondrial protein loading and import, by moderately overexpressing the nuclear-encoded adenine nucleotide translocase, Ant1.

Saliva RNA biomarkers predict concussion duration and detect symptom recovery: a comparison with balance and cognitive testing.

Objective: The goals of this study were to assess the ability of salivary non-coding RNA (ncRNA) levels to predict post-concussion symptoms lasting ≥ 21 days, and to examine the ability of ncRNAs to identify recovery compared to cognition and balance.

Methods: RNA sequencing was performed on 505 saliva samples obtained longitudinally from 112 individuals (8-24-years-old) with mild traumatic brain injury (mTBI). Initial samples were obtained ≤ 14 days post-injury, and follow-up samples were obtained ≥ 21 days post-injury.

Longitudinal stability of salivary microRNA biomarkers in children and adolescents with autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is a complex neurological condition with increasing prevalence. Few tools accurately predict the developmental trajectory of children with ASD. Such tools would allow clinicians to provide accurate prognoses and track the efficacy of therapeutic interventions.

Co-quantification of crAssphage increases confidence in wastewater-based epidemiology for SARS-CoV-2 in low prevalence areas.

Wastewater surveillance of SARS-CoV-2 RNA is increasingly being incorporated into public health efforts to respond to the COVID-19 pandemic. In order to obtain the maximum benefit from these efforts, approaches to wastewater monitoring need to be rapid, sensitive, and relatable to relevant epidemiological parameters. In this study, we present an ultracentrifugation-based method for the concentration of SARS-CoV-2 wastewater RNA and use crAssphage, a bacteriophage specific to the human gut, to help account for RNA loss during transit in the wastewater system and sample processing.

Evidence-based use of scalable biomarkers to increase diagnostic efficiency and decrease the lifetime costs of autism.

Challenges associated with the current screening and diagnostic process for autism spectrum disorder (ASD) in the US cause a significant delay in the initiation of evidence-based interventions at an early age when treatments are most effective. The present study shows how implementing a second-order diagnostic measure to high risk cases initially flagged positive from screening tools can further inform clinical judgment and substantially improve early identification. We use two example measures for the purposes of this demonstration; a saliva test and eye-tracking technology, both scalable and easy-to-implement biomarkers recently introduced in ASD research.

Trajectory of change in brain complement factors from neonatal to young adult humans.

Immune system components also regulate synapse formation and refinement in neurodevelopment. The complement pathway, associated with cell lysis and phagocytosis, is implicated in synaptic elimination. Aberrant adolescent synaptic pruning may underpin schizophrenia onset; thus, changes in cortical complement activity during human development are of major interest.

Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing.

Background: Early, accurate diagnosis of mild traumatic brain injury (mTBI) can improve clinical outcomes for patients, but mTBI remains difficult to diagnose because of reliance on subjective symptom reports. An objective biomarker could increase diagnostic accuracy and improve clinical outcomes. The aim of this study was to assess the ability of salivary noncoding RNA (ncRNA) to serve as a diagnostic adjunct to current clinical tools.