UW Neurological Surgery Recent PubMed Publications

Latrophilin-3 disruption: Effects on brain and behavior

4 years 4 months ago
Latrophilin-3 (LPHN3), a G-protein-coupled receptor belonging to the adhesion subfamily, is a regulator of synaptic function and maintenance in brain regions that mediate locomotor activity, attention, and memory for location and path. Variants of LPHN3 are associated with increased risk for attention deficit hyperactivity disorder (ADHD) in some patients. Here we review the role of LPHN3 in the central nervous system (CNS). We describe synaptic localization of LPHN3, its trans-synaptic binding...
Samantha L Regan

Computationally efficient whole-genome regression for quantitative and binary traits

4 years 4 months ago
Genome-wide association analysis of cohorts with thousands of phenotypes is computationally expensive, particularly when accounting for sample relatedness or population structure. Here we present a novel machine-learning method called REGENIE for fitting a whole-genome regression model for quantitative and binary phenotypes that is substantially faster than alternatives in multi-trait analyses while maintaining statistical efficiency. The method naturally accommodates parallel analysis of...
Joelle Mbatchou

AUTS2 Regulates RNA Metabolism and Dentate Gyrus Development in Mice

4 years 4 months ago
Human AUTS2 mutations are linked to a syndrome of intellectual disability, autistic features, epilepsy, and other neurological and somatic disorders. Although it is known that this unique gene is highly expressed in developing cerebral cortex, the molecular and developmental functions of AUTS2 protein remain unclear. Using proteomics methods to identify AUTS2 binding partners in neonatal mouse cerebral cortex, we found that AUTS2 associates with multiple proteins that regulate RNA transcription,...
Anthony S Castanza

A Pilot Prospective Observational Study of Cerebral Autoregulation and 12-Month Outcomes in Children With Complex Mild Traumatic Brain Injury: The Argument for Sufficiency Conditions Affecting TBI Outcomes

4 years 4 months ago
CONCLUSION: Two-thirds of children with complex mild TBI experienced incomplete functional recovery at 1 year. The co-occurrence of hypotension and cerebral autoregulation may be a sufficiency condition needed to affect TBI outcomes.
Thanyalak Thamjamrassri

Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction

4 years 4 months ago
CONCLUSIONS: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.
Sean P Murphy

ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport

4 years 5 months ago
Despite new advances on the functions of ER chaperones at the cell surface, the translocation mechanisms whereby these chaperones can escape from the ER to the cell surface are just emerging. Previously we reported that in many cancer types, upon ER stress, IRE1α binds to and triggers SRC activation resulting in KDEL receptor dispersion from the Golgi and suppression of retrograde transport. In this study, using a combination of molecular, biochemical, and imaging approaches, we discovered that...
Richard Van Krieken

The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection

4 years 5 months ago
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 global pandemic, utilizes the host receptor angiotensin-converting enzyme 2 (ACE2) for viral entry. However, other host factors might also play important roles in SARS-CoV-2 infection, providing new directions for antiviral treatments. GRP78 is a stress-inducible chaperone important for entry and infectivity for many viruses. Recent molecular docking analyses revealed putative interaction...
Anthony J Carlos

Isoalantolactone Increases the Sensitivity of Prostate Cancer Cells to Cisplatin Treatment by Inducing Oxidative Stress

4 years 5 months ago
Prostate cancer is the most common malignancy among men worldwide. Platinum (II)-based chemotherapy has been used to treat a number of malignancies including prostate cancer. However, the potential of cisplatin for treating prostate cancer is restricted owing to its limited efficacy and toxic side effects. Combination therapies have been proposed to increase the efficacy and reduce the toxic side effects. In the present study, we investigated how isoalantolactone (IATL), a sesquiterpene lactone...
Hang Huang

Maturing heart muscle cells: Mechanisms and transcriptomic insights

4 years 5 months ago
Cardiomyocyte (CM) maturation is the transformation of differentiated fetal CMs into adult CMs that involves changes in morphology, cell function and metabolism, and the transcriptome. This process is, however, incomplete and ultimately arrested in pluripotent stem cell-derived CMs (PSC-CMs) in culture, which hinders their broad biomedical application. For this reason, enormous efforts are currently being made with the goal of generating mature PSC-CMs. In this review, we summarize key aspects...
Sean A Murphy

Cost-effectiveness implications of increasing the efficiency of the extended-release naltrexone induction process for the treatment of opioid use disorder: a secondary analysis

4 years 5 months ago
CONCLUSION: Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the health-care sector perspective over 24-36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.
Sean M Murphy

"What Will Happen If I Say Yes?" Perspectives on a Standardized Firearm Access Question Among Adults With Depressive Symptoms

4 years 5 months ago
CONCLUSIONS: Clarifying the purpose and use of routine firearm access assessment, contextualizing firearm questions within injury prevention broadly, and addressing misconceptions about suicide prevention may help encourage disclosure of firearm access and increase the patient centeredness of this practice.
Julie E Richards

Association of co-occurring opioid or other substance use disorders with increased healthcare utilization in patients with depression

4 years 5 months ago
Substance use disorders (SUDs) commonly co-occur with mental illness. However, the ongoing addiction crisis raises the question of how opioid use disorder (OUD) impacts healthcare utilization relative to other SUDs. This study examines the utilization patterns of patients with major depressive disorder (MDD) and: (1) co-occurring OUD (MDD-OUD); (2) a co-occurring SUD other than OUD (MDD-NOUD); and (3) no co-occurring SUD (MDD-NSUD). We analyzed electronic health records (EHRs) derived from...
Veer Vekaria

Association of Early Multiple Organ Dysfunction With Clinical and Functional Outcomes Over the Year Following Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

4 years 5 months ago
CONCLUSIONS: Early multiple organ dysfunction following moderate-severe traumatic brain injury is common and independently impacts multiple domains (mortality, function, and disability) over the year following injury. Further research is necessary to understand underlying mechanisms, improve early recognition, and optimize management strategies.
Vijay Krishnamoorthy

Endoplasmic reticulum chaperone GRP78/BiP is critical for mutant Kras-driven lung tumorigenesis

4 years 5 months ago
Lung cancer is the leading cause of cancer mortality worldwide and KRAS is the most commonly mutated gene in lung adenocarcinoma (LUAD). The 78-kDa glucose-regulated protein GRP78/BiP is a key endoplasmic reticulum chaperone protein and a major pro-survival effector of the unfolded protein response (UPR). Analysis of the Cancer Genome Atlas database and immunostain of patient tissues revealed that compared to normal lung, GRP78 expression is generally elevated in human lung cancers, including...
Daisy Flores Rangel
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