Frank A. Middleton
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View article: Increased TNF Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains
Increased TNF Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains Open
View article: Viral genetic variability in wastewater predicts changes in community infection levels
Viral genetic variability in wastewater predicts changes in community infection levels Open
Sequencing viruses found in community wastewater facilitates the study of diversity in circulating viruses at the population level. By analyzing 12,290 wastewater samples collected between January 2023 and April 2025 in New York State, USA…
View article: Mitochondrial protein import stress augments α-synuclein aggregation and neural damage independent of bioenergetics
Mitochondrial protein import stress augments α-synuclein aggregation and neural damage independent of bioenergetics Open
View article: 636. MICROGLIA/MACROPHAGE TRANSCRIPTS ARE INCREASED IN NEUROINFLAMMATORY SCHIZOPHRENIA AND BIPOLAR DISORDER MIDBRAINS
636. MICROGLIA/MACROPHAGE TRANSCRIPTS ARE INCREASED IN NEUROINFLAMMATORY SCHIZOPHRENIA AND BIPOLAR DISORDER MIDBRAINS Open
Background We have previously found increased microglial/macrophage transcripts in the midbrains of people with schizophrenia that display a high-inflammation profile. However, contradictory results of decreased and unchanged markers have …
View article: LungGENIE: the lung gene-expression and network imputation engine
LungGENIE: the lung gene-expression and network imputation engine Open
Background Few cohorts have study populations large enough to conduct molecular analysis of ex vivo lung tissue for genomic analyses. Transcriptome imputation is a non-invasive alternative with many potential applications. We present a nov…
View article: CELL DEATH TRANSCRIPTS OF THE TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY ARE INCREASED IN THE MIDBRAINS OF SCHIZOPHRENIA AND BIPOLAR DISORDER WITH HIGH INFLAMMATION AND ARE NEGATIVELY ASSOCIATED WITH DOPAMINE TRANSCRIPTS
CELL DEATH TRANSCRIPTS OF THE TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY ARE INCREASED IN THE MIDBRAINS OF SCHIZOPHRENIA AND BIPOLAR DISORDER WITH HIGH INFLAMMATION AND ARE NEGATIVELY ASSOCIATED WITH DOPAMINE TRANSCRIPTS Open
Background Whereas it is still unclear if cell death occurs in the brains of people with schizophrenia and bipolar disorder, it is well established that neuroinflammation and dopaminergic imbalances are key neuropathological hallmarks of t…
View article: Discovery of novel blood-brain barrier neuropathology in schizophrenia and bipolar disorder midbrain
Discovery of novel blood-brain barrier neuropathology in schizophrenia and bipolar disorder midbrain Open
Elevated pro-inflammatory cytokines and increased macrophage densities have been found in a subgroup (~30-40%) of schizophrenia and bipolar disorder brains. However, the extent to which neuroinflammation influences the blood-brain barrier …
View article: Dengue Virus Structural Proteins Are Expressed on the Surface of DENV-Infected Cells and Are a Target for Antibody-Dependent Cellular Phagocytosis
Dengue Virus Structural Proteins Are Expressed on the Surface of DENV-Infected Cells and Are a Target for Antibody-Dependent Cellular Phagocytosis Open
Background Dengue virus (DENV) is an arboviral pathogen found in >100 countries and a source of significant morbidity and mortality. While the mechanisms underpinning the pathophysiology of severe Dengue are incompletely understood, it …
View article: Increased Parenchymal Macrophages are associated with decreased Tyrosine Hydroxylase mRNA levels in the Substantia Nigra of people with Schizophrenia and Bipolar Disorder
Increased Parenchymal Macrophages are associated with decreased Tyrosine Hydroxylase mRNA levels in the Substantia Nigra of people with Schizophrenia and Bipolar Disorder Open
View article: Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation
Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation Open
View article: mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency
mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency Open
View article: Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants
Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants Open
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 s…
View article: Mitochondrial protein import clogging as a mechanism of disease
Mitochondrial protein import clogging as a mechanism of disease Open
Mitochondrial biogenesis requires the import of >1,000 mitochondrial preproteins from the cytosol. Most studies on mitochondrial protein import are focused on the core import machinery. Whether and how the biophysical properties of substra…
View article: Systemic Proteome Phenotypes Reveal Defective Metabolic Flexibility in Mecp2 Mutants
Systemic Proteome Phenotypes Reveal Defective Metabolic Flexibility in Mecp2 Mutants Open
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 s…
View article: Author response: Mitochondrial protein import clogging as a mechanism of disease
Author response: Mitochondrial protein import clogging as a mechanism of disease Open
Full text Figures and data Side by side Abstract Editor's evaluation eLife digest Introduction Results Discussion Materials and methods Appendix 1 Data availability References Decision letter Author response Article and author information …
View article: Clinical Features of Genetic Resilience in Chronic Obstructive Pulmonary Disease
Clinical Features of Genetic Resilience in Chronic Obstructive Pulmonary Disease Open
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. H…
View article: Publisher Correction: Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis
Publisher Correction: Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis Open
View article: Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis
Cytosolic aldose metabolism contributes to progression from cirrhosis to hepatocarcinogenesis Open
View article: The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling
The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling Open
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 a…
View article: Mitochondrial protein import stress augments α-synuclein aggregation and neurodegeneration independent of bioenergetics
Mitochondrial protein import stress augments α-synuclein aggregation and neurodegeneration independent of bioenergetics Open
Several genetic and environmental risk factors for Parkinson’s disease have been identified that converge on mitochondria as central elements in the disease process. However, the mechanisms by which mitochondrial dysfunction contributes to…
View article: Mitochondrial protein import clogging as a mechanism of disease
Mitochondrial protein import clogging as a mechanism of disease Open
Mitochondrial biogenesis requires the import of >1,000 mitochondrial preproteins from the cytosol. Most studies on mitochondrial protein import are focused on the core import machinery. Whether and how the biophysical properties of substra…
View article: Changes in Cytokine and Cytokine Receptor Levels During Postnatal Development of the Human Dorsolateral Prefrontal Cortex
Changes in Cytokine and Cytokine Receptor Levels During Postnatal Development of the Human Dorsolateral Prefrontal Cortex Open
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 o…
View article: Infection with Borrelia burgdorferi Increases the Replication and Dissemination of Coinfecting Powassan Virus in Ixodes scapularis Ticks
Infection with Borrelia burgdorferi Increases the Replication and Dissemination of Coinfecting Powassan Virus in Ixodes scapularis Ticks Open
Powassan virus (POWV) is a tick-borne neuroinvasive flavivirus endemic to North America. It is generally transmitted by the tick, Ixodes scapularis. This species also transmits Borrelia burgdorferi, the causative agent of Lyme disease. Inf…
View article: Distinct Phenotypes of Inflammation Associated Macrophages and Microglia in the Prefrontal Cortex Schizophrenia Compared to Controls
Distinct Phenotypes of Inflammation Associated Macrophages and Microglia in the Prefrontal Cortex Schizophrenia Compared to Controls Open
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-…
View article: High Sensitivity and Specificity of Dormitory-Level Wastewater Surveillance for COVID-19 during Fall Semester 2020 at Syracuse University, New York
High Sensitivity and Specificity of Dormitory-Level Wastewater Surveillance for COVID-19 during Fall Semester 2020 at Syracuse University, New York Open
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…
View article: Coupling freedom from disease principles and early warning from wastewater surveillance to improve health security
Coupling freedom from disease principles and early warning from wastewater surveillance to improve health security Open
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 disea…
View article: Development and Validation of Two RT-qPCR Diagnostic Assays for Detecting Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Targets across Two Specimen Types
Development and Validation of Two RT-qPCR Diagnostic Assays for Detecting Severe Acute Respiratory Syndrome Coronavirus 2 Genomic Targets across Two Specimen Types Open
View article: Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine
Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine Open
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 …
View article: Cytosolic adaptation to mitochondria-induced proteostatic stress causes progressive muscle wasting
Cytosolic adaptation to mitochondria-induced proteostatic stress causes progressive muscle wasting Open
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 moder…
View article: Coupling freedom from disease principles and early warning from wastewater surveillance to improve health security
Coupling freedom from disease principles and early warning from wastewater surveillance to improve health security Open
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 disea…