Digital Commons Network^™

Intravenous Thrombolysis In Patients On Direct Oral Anticoagulants: Analysis Of The Get With The Guidelines Stroke Registry, Shadi Yaghi, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use.

METHODS: This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from …

Association Between Monoclonal Gammopathy Of Undetermined Significance And Cardiovascular Disease Risk: A Veterans Health Administration Study, Tzeyu L Michaud, Mei Wang, Daphne R Friedman, Lawrence Liu, Theodore S Thomas, Kristen M Sanfilippo, Graham A Colditz, Martin W Schoen, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease (CVD). However, its potential to provide additional prognostic information beyond traditional CVD risk assessments remains unknown. This study aimed to examine the association between MGUS and incident CVD and to determine whether MGUS status offers additional prognostic value beyond the established atherosclerotic cardiovascular disease risk calculation.

METHODS: We conducted a retrospective, matched observational study using 2010 to 2021 Veterans Health Administration data. MGUS status, confirmed through a validated natural language processing algorithm, were 1:5 matched to individuals without MGUS. The outcome of interest was …

Neuronal Subtype Governs Amyloid Structure, Cellular Response, And Cognitive Outcome In Genetically Targeted App Mouse Models, Gabriella A Perez, Zoe Lai, George A Edwards Iii, Jacob M Dundee, Shannon N Leahy, Chuangye Qi, Yanyan Qi, Ye-Jin Park, Tzu-Chiao Lu, M Danish Uddin, Rong Zhao, Hui Zheng, Hongjie Li, Joanna L Jankowsky

2020-Current year OA Pubs

Pathological heterogeneity is increasingly appreciated in Alzheimer’s disease, yet we do not know how distinct aggregate conformations arise or influence cognitive outcomes. In an amyloid mouse model, we found that different brain regions formed structurally distinct Aβ deposits, prompting us to test whether neuronal subtypes shape aggregate conformation. To address this, we created transgenic mice expressing the same APP construct in either glutamatergic or GABAergic neurons. APP expression in GABAergic neurons resulted in diffuse plaques with high Aβ42/Aβ40 ratios and minimal gliosis, while glutamatergic expression produced neuritic plaques with activated glia. Despite similar Aβ levels, only mice with neuritic plaques …

Durability Of The Benefit Of Vagus Nerve Stimulation In Markedly Treatment-Resistant Major Depression: A Recover Trial Report, Charles R Conway, Christopher L Kriedt, Charles F Zorumski, Hunter Brown, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Greater levels of treatment resistance in major depressive disorder (MDD) are associated with lower rates of initial benefit and higher rates of relapse (lower durability).

OBJECTIVE: Characterize depressive symptoms, function, and quality of life (QoL) over 24 months of adjunctive vagus nerve stimulation (VNS) in participants with markedly treatment-resistant depression.

DESIGN: Prospective, open-label, single-arm, long-term extension study (RECOVER) conducted from September 2019 to April 2025.

SETTING: Outpatient.

PARTICIPANTS: Adults with moderate-severe MDD with ≥ 4 failed antidepressant trials in the current episode, randomized to blinded, adjunctive VNS for 12 months, who subsequently received open-label, adjunctive VNS for 12 additional …

Postoperative Lymph Is A Proximal Source Of Ctdna For Detection Of Recurrence In Hpv-Independent Head And Neck Cancer, Seka Lazare, Noah Earland, Peter Harris, Ricardo Ramirez, Benjamin Wahle, Sid Puram, Doug Adkins, Wade Thorstad, Rebecca Chernock, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

PURPOSE: Relapse is a major cause of failure in human papillomavirus-independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains ("lymph") 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma.

EXPERIMENTAL DESIGN: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. …

Mass Spectrometry Footprinting Reveals How Kinetic Stabilizers Counteract Transthyretin Dynamics Altered By Pathogenic Mutations, Francisca Pinheiro, Ravi Kant, Saketh Chemuru, Nathalia Varejão, Adrián Velázquez-Campoy, David Reverter, Irantzu Pallarès, Michael L Gross, Salvador Ventura

2020-Current year OA Pubs

The aggregation of transthyretin (TTR) results in life-threatening transthyretin amyloidosis. Familial forms of the disease arise from point mutations that destabilize the TTR tetramer, leading to its dissociation and/or monomer unfolding and subsequent formation of amyloid fibrils. Small molecules that kinetically stabilize the native tetramer effectively inhibit this aggregation. Although over 300 X-ray crystal structures of TTR have been determined, these data refer to a static structure and do not capture the conformational effects of mutations and ligand binding. Here, we demonstrate that hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) offer critical …

Polymer Conformational Entropy As The Driver Of Complex Coacervation, Tommaso Inzani, Giovanni Nava, Marco Buscaglia, Andrea Soranno, Alessandro Gori, Greta Bergamaschi, Samir Suweis, Amos Maritan, Tommaso Bellini

2020-Current year OA Pubs

Understanding the mechanisms leading to complex coacervation is a fundamental challenge in biomolecular sciences. Here, we explored the condensation transition and pretransitional behavior of an archetypal system consisting of polyuridylic acid chains (PolyU) and short cationic peptides in buffered aqueous solutions. By combining static and dynamic light scattering with confocal microscopy, we determined the location of the transition and the partitioning of PolyU and peptides between the coexisting phases as a function of the total peptides/PolyU ratio. We find that upon adding peptides in the system, the size of PolyU coils in the single-phase region is progressively reduced by peptide-mediated …

Omg! A Proteomic Determinant Of Neurodegenerative Resiliency, Michael R Duggan, Muhammad Ali, Menghan Liu, Ying Xu, Daniel Western, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer's disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation.

METHODS: After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG's role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, …

Accurate Chromatin Marks Peak Calling With Omnipeak, Oleg Shpynov, Maxim N Artyomov

2020-Current year OA Pubs

Chromatin immunoprecipitation sequencing (ChIP-seq) is a widely used technique for identifying transcription-factor binding and histone modifications across the genome. Peaks in ChIP-seq data vary in length depending on the biological context, from narrow transcription factor binding sites to broad histone modification domains. However, commonly used peak-calling tools are tailored to the specific types of data and struggle to consistently handle various peak lengths, datasets of varying quality, and missing control tracks-common issues in comparative or meta-analyses. These limitations are addressed with Omnipeak, a universal unsupervised peak-calling algorithm based on a constrained three-state hidden Markov model. Omnipeak accurately models global genomic …

Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle

2020-Current year OA Pubs

Ca2+- and voltage-activated BK-type K+ channels are influenced profoundly by associated regulatory subunits, including β subunits (Kcnmb1-4; β1-β4). Although overlap in expression of different BK β subunits occurs in native tissues, whether they can coassemble in the same channel complex is not known. We coexpress β2 and β3a subunits together with BK α and, through a combination of macroscopic and single-channel recordings, along with quantitative pull-down of tagged subunits, test whether coassembly can occur. We evaluate two models: (1) random mixing in which β2 and β3a subunits coassemble in the same channels, and (2) segregation in which β2 and β3a …

Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda

2020-Current year OA Pubs

Cyclic nucleotide-binding domain (CNBD) channels are critical components of numerous bioelectrical processes, including cardiac pacemaking, neuronal signaling, phototransduction in the eye, and stomatal regulation in plants. While members of this channel family share a conserved overall structure, they exhibit striking differences in voltage sensitivity. Hyperpolarization-activated cyclic nucleotide-gated channels are activated by membrane hyperpolarization, whereas ether-à-go-go channels open upon depolarization. Mutagenesis and chimeragenesis studies have revealed that some mutants display bipolar gating behavior-remaining closed at intermediate membrane potentials but capable of opening in response to both hyperpolarization and depolarization. Remarkably, in certain cases, just a few mutations are sufficient to reverse …

Environmental Enteric Dysfunction In Well-Nourished And Undernourished Women In Bangladesh, Mustafa Mahfuz, Md Shabab Hossain, Ar-Rafi Khan, Mehjabin Tishan Mahfuz, Rumana Sharmin, A H M Rezwan, Musarrat Tasnim, S M Tafsir Hasan, S M Khodeza Nahar Begum, M Masudur Rahman, Michael J Barratt, Jeffrey I Gordon, Tahmeed Ahmed

2020-Current year OA Pubs

INTRODUCTION: Environmental Enteric Dysfunction (EED) is a subacute inflammation of the small intestinal (SI) mucosa associated with undernutrition and perturbation of the SI microbiota. Its diagnosis relies on histopathological assessment of small intestinal biopsies, with a lack of validated biomarkers contributing to underdiagnosis. This study assessed the prevalence and histological features of EED in undernourished Bangladeshi women living in an urban slum in Dhaka, compared to well-nourished women from slum and non-slum areas, and examined the factors associated with histologically confirmed EED.

METHODS: This analysis included non-pregnant, non-lactating Bangladeshi women aged 18-45 years classified by location of residence and nutritional …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H B Wu, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Prospective Audit And Feedback By Antibiotic Stewardship Teams To Reduce Antibiotic Overuse At Hospital Discharge: A Stepped-Wedge Cluster-Randomized Clinical Trial, Daniel J Livorsi, Michael Joshua Hendrix, Erin Rachmiel, Jahnavi Bongu, Alice Bewley, Kevin Hsueh, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Antibiotics prescribed at hospital discharge are frequently unnecessary or suboptimal. Strategies to improve prescribing are not well defined.

OBJECTIVE: To evaluate whether a discharge-focused prospective audit and feedback process decreases antibiotic overuse at hospital discharge.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted across participating units at 10 hospitals with antibiotic stewardship (AS) teams and supporting staff from December 5, 2022, to November 17, 2023. After a 24-week baseline period, 1 hospital crossed into the intervention arm every 2 weeks.

INTERVENTION: The intervention consisted of disseminating institutional guidelines for oral antibiotic step-down to frontline prescribers and …

Cumulative Lifespan Stress, Inflammation, And Racial Disparities In Mortality Between Black And White Adults, Isaiah D Spears, Aaron J Gorelik, Sara A Norton, Michael J Boudreaux, Megan W Wolk, Jayne Siudzinski, Sarah E Paul, Mary A Cox, Cynthia E Rogers, Thomas F Oltmanns, Patrick L Hill, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: In the US, Black individuals experience higher mortality risk than White individuals. Greater stress exposure and its biological sequelae are theorized to drive this heightened risk.

OBJECTIVE: To evaluate whether greater cumulative lifespan stress exposure and elevated inflammation are associated with increased mortality risk among Black compared with White US individuals.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study (St Louis Personality and Aging Network) recruited participants from 2007 to 2011 from the St Louis, Missouri, metropolitan area. Participants were required to have a mailing address to permit longitudinal follow-up and sixth grade reading level to facilitate understanding of …

White Matter Hyperintensity Burden And Decline In Driving Performance Among Older Adults, Madhur Parihar, Yasheng Chen, Byron Xu, Semere Bekena, Ramkrishna K Singh, Yiqi Zhu, Jean-Francois Trani, Jin-Moo Lee, David B Carr, Chia-Ling Phuah, Ganesh M Babulal, Driving Real-World In-Vehicle Evaluation System (Drives) Project

2020-Current year OA Pubs

IMPORTANCE: White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.

OBJECTIVE: To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study enrolled community-dwelling older adults (≥65 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected …

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …

Pacs Viewbook 2026-2027, Program In Audiology And Communication Sciences

PACS News

No abstract provided.

A Generalist Institutional Data Repository Offering Both Open And Restricted Access To Support Nih Data Sharing Compliance., Seonyoung Kim, Xing Jian, Marcy Vana

Becker Library Publications and Presentations

In response to the 2023 NIH Data Management and Sharing (DMS) Policy, Washington University School of Medicine in St. Louis launched Digital Commons Data@Becker, a generalist institutional data repository supporting both open and restricted access to research data. Managed by Bernard Becker Medical Library's DMS Team, the repository offers a fully mediated curation workflow that guides researchers through consultation, metadata capture, documentation, and quality control. Draft Digital Object Identifiers (DOIs) can be issued once access type is determined, with final DOI publication following curation and QC. Restricted datasets require Human Research Protection Office (HRPO) review and Data Transfer and Use …

Nanoparticle Albumin-Bound Paclitaxel And Nivolumab For Pd-1 Inhibitor-Refractory Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Douglas Adkins, Jessica C Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt

2020-Current year OA Pubs

INTRODUCTION: Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (nab)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.

METHODS: In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received nab-paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were …

Perception Of Dementia Risk Among Black Adults: An Ecological Analysis Of Causal Loop Diagrams With A Structural And Social Determinant Of Health Composite Index, Jean-Francois Trani, Ramkrishna K Singh, Alexis Ib Walker, Semere Bekena, Yiqi Zhu, Ganesh M Babulal, Robbie Hart

2020-Current year OA Pubs

INTRODUCTION: To investigate drivers of dementia risk disparities among older Black Americans using a community-based system dynamics (CBSD) approach.

METHODS: Over 18 months, 234 participants created 36 causal loop diagrams (CLDs) on dementia risk. An ecological analysis compared structural differences across groups based on scores on a structural and social determinants of health composite index (S/SDOH-CI).

RESULTS: Groups in the highest SDOH-CI quantile were more likely to identify key protective pathways linking mental health, substance use, exercise, medication, and community support to reduce dementia risk. In contrast, fewer than 25% of low-SDOH-CI groups identified these connections, and under 15% recognized …

Treating Alzheimer's Disease In A Person Living With Hiv, David B Clifford, Tammie L S Benzinger, Jee-Young Han, Savannah Powles, Madeline Paczynski, Beau M Ances, J William Campbell

2020-Current year OA Pubs

INTRODUCTION: Human immunodeficiency virus (HIV) therapies now support survival into advanced ages by suppressing HIV replication and preserving immune function. Alzheimer's disease (AD), the most common neurologic degenerative condition, may now be treated with anti-amyloid therapies (AAT). HIV was an exclusionary criterion in clinical trials for AAT, leaving the safety and efficacy of these medications unknown in this setting.

METHODS: We report the development of AD supported by careful evaluations and biomarkers over a 10-year period in a person living with well-controlled HIV infection.

RESULTS: AD was diagnosed with consistent clinical and biomarker evidence. AAT was successfully administered without complications. …

Reliability Of Remote Self-Administered Web-Based Digital Cognitive Measures And Comparison To In-Person Neuropsychological Tests: Stricker Learning Span, Symbols Test, And The Mayo Test Drive Screening Battery Composite, Morgan A Hughes, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

INTRODUCTION: We describe the reliability of remote self-administered digital cognitive measures completed via the Mayo Test Drive (MTD) web-based platform.

METHODS: A total of 1846 participants (mean age = 70, SD = 12, range 31-101; 48% male; 96% White; 99% non-Hispanic; 97% cognitively unimpaired) with two to four complete MTD sessions at ∼7.5-month intervals were included. Test-retest reliability was assessed using single-rating, absolute-agreement, and two-way mixed intraclass correlation coefficients (ICCs) with 95% confidence intervals. ICCs for in-person-administered traditional neuropsychological measures were compared to MTD for a subset of 244 participants. Analyses also compared reliability across demographic, residential, and session context …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G Clina, Beau Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (

RESULTS: People with CHD scored lower for visuospatial ability (

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the …

The Role Of Home Visiting In Addressing Postpartum Care Gaps: Evidence From A Large Community Sample, Aishwarya Vijay, Allison Kemner, Karen Hoerchler, Abigail Edwards, Jeannie C Kelly, Rachel G Tabak, Mark D Huffman, Zainab Mahmoud

2020-Current year OA Pubs

BackgroundMaternal mortality in the United States has doubled over the last two decades, primarily due to cardiovascular disease, with more than half of deaths occurring postpartum. Despite national calls to action, attendance at postpartum clinic visits remains low. The role of alternative care delivery strategies, such as home visiting, remains insufficiently studied.ObjectiveTo describe postpartum clinic visit attendance among participants in a large national home visiting program, identify sociodemographic and clinical factors associated with attendance, and examine how timing and duration of enrollment relate to postpartum follow-up.DesignWe conducted a retrospective cohort study of pregnancy episodes among mothers enrolled in the Parents …

Steroid Hormone Metabolites And Mammographic Breast Density In Premenopausal Women, Ghazaleh Pourali, Kayode A Matthew, Myung Sik Jeon, Chongliang Luo, Gary J Patti, Jingqin Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Steroid hormones influence breast morphology and cellular proliferation and are associated with breast carcinogenesis. However, their associations with mammographic breast density (MBD) are less studied, particularly in premenopausal women. We, therefore, investigated the associations of steroid hormone metabolites with MBD in premenopausal women.

METHODS: Our study included 700 premenopausal women scheduled for screening mammograms. We analyzed 54 steroid hormone metabolites (Metabolon®) and assessed volumetric measures of MBD including volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV) using Volpara. We investigated associations using linear regression modeling to estimate the covariate-adjusted means of VPD, NDV, and DV, corresponding …

Cutibacterium Adaptation To Life On Humans Provides A Potential C Acnes Infection Biomarker, Md Shafiuddin, Wen-Chi Huang, Gabriel William Prather, Jeffrey Ryan Anton, Andrew Lawrence Martin, Sydney Brianna Sillart, Jonathan Z Tang, Michael R Vittori, Michael J Prinsen, Jessica Jane Ninneman, Chandrashekhara Manithody, Jeffrey P Henderson, Alexander W Aleem, Ma Xenia Garcia Ilagan, William H Mccoy 4th

2020-Current year OA Pubs

Propionibacteriaceae appear to have adapted to life on humans during the domestication of cattle. These microbial immigrants formed the genus Cutibacterium, and a descendent of those microbial trailblazers (C acnes) now dominates 25% of human skin. C acnes colonization of human skin requires the protein RoxP. Although all Cutibacteria encode this adaptation to life on humans, nothing like RoxP has been found in any other organism. In this study, we report an extensive assessment of 21 RoxP orthologs, which identified conserved molecular surfaces linked to heme-dependent oligomerization and low pH stability. Our investigation suggests how RoxP helps C acnes dominate …

An Integrated View Of The Structure And Function Of The Human 4d Nucleome, Job Dekker, Ting Wang, Daofeng Li, Et Al.

2020-Current year OA Pubs

The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

Dysregulated Lactate Metabolism Synergizes With Als Genetic Risk Factors To Accelerate Motor Decline, Shweta Tendulkar, Tong Wu, Amy Strickland, Amber R. Hackett, Yurie Sato-Yamada, Xianrong Mao, Yo Sasaki, Jeffrey Milbrandt, A. Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Neurons rely on glial 'lactate shuttling' for metabolic support, which declines with aging and in neurodegenerative disease. Full disruption of lactate shuttling in peripheral nerves causes progressive axon degeneration, but we were interested to understand how partial disruption, a scenario more relevant to aging and disease, contributes to neurodegeneration risk. Pyruvate and lactate are interconverted by lactate dehydrogenases (LDHA and LDHB) in both lactate producing and consuming cells. We therefore began by investigating Ldhb knockout mice (loss of LDHA, the dominant LDH in liver and muscle, caused embryonic lethality), and discovered that they develop progressive neuromuscular junction atrophy and functional …