Digital Commons Network^™

Selective Sweep For An Enhancer Involucrin Allele Identifies Skin Barrier Adaptation Out Of Africa, Mary Elizabeth Mathyer, Erin A. Brettmann, Alina D. Schmidt, Zane A. Goodwin, Inez Y. Oh, Ashley M. Quiggle, Eric Tycksen, Natasha Ramakrishnan, Scot J. Matkovich, Emma Guttman-Yassky, John R. Edwards, Cristina De Guzman Strong

Open Access Publications

No abstract provided.

Co-Evolution Of Tumor And Immune Cells During Progression Of Multiple Myeloma, Ruiyang Liu, Qingsong Gao, Steven M. Foltz, Jared S. Fowles, Lijun Yao, Julia Tianjiao Wang, Song Cao, Hua Sun, Michael C. Wendl, Sunantha Sethuraman, Amila Weerasinghe, Michael P. Rettig, Erik P. Storrs, Christopher J. Yoon, Matthew A. Wyczalkowski, Joshua F. Mcmichael, Daniel R. Kohnen, Justin King, Scott R. Goldsmith, Julie O'Neal, Robert S. Fulton, Catrina C. Fronick, Timothy J. Ley, Reyka G. Jayasinghe, Mark A. Fiala, Stephen T. Oh, John F. Dipersio, Ravi Vij, Li Ding

Open Access Publications

No abstract provided.

Cryo-Em Structure Of Cortical Microtubules From Human Parasite Toxoplasma Gondii Identifies Their Microtubule Inner Proteins, Xiangli Wang, Yong Fu, Wandy L. Beatty, Meisheng Ma, Alan Brown, L. David Sibley, Rui Zhang

Open Access Publications

No abstract provided.

A Voxel-Wise Assessment Of Growth Differences In Infants Developing Autism Spectrum Disorder, A Cárdenas-De-La-Parra, J D Lewis, V S Fonov, K N Botteron, R C Mckinstry, G Gerig, J R Pruett Jr, S R Dager, J T Elison, M A Styner, A C Evans, J Piven, D L Collins, Ibis Network

Open Access Publications

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry …

Multi-Modal Biomarkers Of Low Back Pain: A Machine Learning Approach, Bidhan Lamichhane, Dinal Jayasekera, Rachel Jakes, Matthew F Glasser, Justin Zhang, Chunhui Yang, Derayvia Grimes, Tyler L Frank, Wilson Z Ray, Eric C Leuthardt, Ammar H Hawasli

Open Access Publications

Chronic low back pain (LBP) is a very common health problem worldwide and a major cause of disability. Yet, the lack of quantifiable metrics on which to base clinical decisions leads to imprecise treatments, unnecessary surgery and reduced patient outcomes. Although, the focus of LBP has largely focused on the spine, the literature demonstrates a robust reorganization of the human brain in the setting of LBP. Brain neuroimaging holds promise for the discovery of biomarkers that will improve the treatment of chronic LBP. In this study, we report on morphological changes in cerebral cortical thickness (CT) and resting-state functional connectivity …

Mapping The Molecular And Structural Specialization Of The Skin Basement Membrane For Inter-Tissue Interactions, Ko Tsutsui, Hiroki Machida, Asako Nakagawa, Kyungmin Ahn, Ritsuko Morita, Kiyotoshi Sekiguchi, Jeffrey H. Miner, Hironobu Fujiwara

Open Access Publications

No abstract provided.

A Decade In Review After Idiopathic Scoliosis Was First Called A Complex Trait-A Tribute To The Late Dr. Yves Cotrel For His Support In Studies Of Etiology Of Scoliosis, Nelson L S Tang, Matthew B Dobbs, Christina A Gurnett, Yong Qiu, T P Lam, Jack C Y Cheng, Nancy Hadley-Miller

Open Access Publications

Adolescent Idiopathic Scoliosis (AIS) is a prevalent and important spine disorder in the pediatric age group. An increased family tendency was observed for a long time, but the underlying genetic mechanism was uncertain. In 1999, Dr. Yves Cotrel founded the Cotrel Foundation in the Institut de France, which supported collaboration of international researchers to work together to better understand the etiology of AIS. This new concept of AIS as a complex trait evolved in this setting among researchers who joined the annual Cotrel meetings. It is now over a decade since the first proposal of the complex trait genetic model …

The Treatment Gap In Osteoporosis, Nazia Ayub, Malak Faraj, Sam Ghatan, Joannes A A Reijers, Nicola Napoli, Ling Oei

Open Access Publications

Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is made by measuring bone mineral density. Medications used for the treatment of osteoporosis are bisphosphonates, denosumab, raloxifene, and teriparatide. Recently, romosozumab has been added as well. In recent years, a number of advances have been made in the field of diagnostic methods and the diverse …

Consequences Of Sur2[A478v] Mutation In Skeletal Muscle Of Murine Model Of Cantu Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Giuseppe Passantino, Antonietta Mele, Giulia Maria Camerino, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the

Global Waves Synchronize The Brain's Functional Systems With Fluctuating Arousal, Ryan V Raut, Abraham Z Snyder, Anish Mitra, Dov Yellin, Naotaka Fujii, Rafael Malach, Marcus E Raichle

Open Access Publications

We propose and empirically support a parsimonious account of intrinsic, brain-wide spatiotemporal organization arising from traveling waves linked to arousal. We hypothesize that these waves are the predominant physiological process reflected in spontaneous functional magnetic resonance imaging (fMRI) signal fluctuations. The correlation structure ("functional connectivity") of these fluctuations recapitulates the large-scale functional organization of the brain. However, a unifying physiological account of this structure has so far been lacking. Here, using fMRI in humans, we show that ongoing arousal fluctuations are associated with global waves of activity that slowly propagate in parallel throughout the neocortex, thalamus, striatum, and cerebellum. We …

The Top 100 Cited Papers In The Field Of Iron Deficiency In Humans: A Bibliometric Study, John L. Frater

Open Access Publications

No abstract provided.

Genomic And Clinical Characterization Of Early T-Cell Precursor Lymphoblastic Lymphoma, Xinjie Xu, Christian N. Paxton, Robert J. Hayashi, Kimberly P. Dunsmore, Stuart S. Winter, Stephen P. Hunger, Naomi J. Winick, William L. Carroll, Mignon L. Loh, Meenakshi Devidas, Thomas G. Gross, Catherine M. Bollard, Sherrie L. Perkins, Rodney R. Miles

Open Access Publications

No abstract provided.

Taxonomic Changes In The Gut Microbiota Are Associated With Cartilage Damage Independent Of Adiposity, High Fat Diet, And Joint Injury, Kelsey H. Collins, Drew J. Schwartz, Kristin L. Lenz, Charles A. Harris, Farshid Guilak

Open Access Publications

No abstract provided.

Restoration Of The Molecular Clock Is Tumor Suppressive In Neuroblastoma, Myrthala Moreno-Smith, Thomas P. Burris, Et Al.

Open Access Publications

No abstract provided.

Focused Crispr‑Cas9 Genetic Screening Reveals Uso1 As A Vulnerability In B‑Cell Acute Lymphoblastic Leukemia, Amit Kumar Jaiswal, Hellen Truong, Tiffany M. Tran, Tasha L. Lin, David Casero, Michael O. Alberti, Dinesh S. Rao

Open Access Publications

No abstract provided.

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Gordon I. Smith, Samuel Klein, Et Al

Open Access Publications

No abstract provided.

Transcriptional-Regulatory Convergence Across Functional Mdd Risk Variants Identified By Massively Parallel Reporter Assays, Bernard Mulvey, Joseph D. Dougherty

Open Access Publications

No abstract provided.

Mismatch Repair Deficiency Predicts Response To Her2 Blockade In Her2-Negative Breast Cancer, Nindo B. Punturi, Sinem Seker, Vaishnavi Devarakonda, Aloran Mazumder, Rashi Kalra, Ching Hui Chen, Shunqiang Li, Tina Primeau, Matthew J. Ellis, Shyam M. Kavuri, Svasti Haricharan

Open Access Publications

No abstract provided.

A Multi-Step Nucleation Process Determines The Kinetics Of Prion-Like Domain Phase Separation, Erik W. Martin, Tyler S. Harmon, Jesse B. Hopkins, Srinivas Chakravarthy, J. Jeremías Incicco, Peter Schuck, Andrea Soranno, Tanja Mittag

Open Access Publications

No abstract provided.

Reducing Auditory Nerve Excitability By Acute Antagonism Of Ca2+-Permeable Ampa Receptors, Amit Walia, Choongheon Lee, Jared Hartsock, Shawn S Goodman, Roland Dolle, Alec N Salt, Jeffery T Lichtenhan, Mark A Rutherford

Open Access Publications

Hearing depends on glutamatergic synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are tetramers, where inclusion of the GluA2 subunit reduces overall channel conductance and Ca

Markers Of Early Changes In Cognition Across Cohorts Of Adults With Down Syndrome At Risk Of Alzheimer's Disease, Andrew J Aschenbrenner, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.

Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria.

Results: There were common cognitive domains across site composites, which were sensitive to …

Distinct Microrna Profiles In The Perilymph And Serum Of Patients With Menière's Disease, Matthew Shew, Helena Wichova, Madeleine St Peter, Athanasia Warnecke, Hinrich Staecker

Open Access Publications

No abstract provided.

Maturation Of Heterogeneity In Afferent Synapse Ultrastructure In The Mouse Cochlea, Shelby A Payne, Matthew S Joens, Heather Chung, Natalie Skigen, Adam Frank, Sonali Gattani, Kya Vaughn, Allison Schwed, Matt Nester, Atri Bhattacharyya, Guhan Iyer, Bethany Davis, Jason Carlquist, Honey Patel, James A J Fitzpatrick, Mark A Rutherford

Open Access Publications

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured …

Infiltration By Cxcl10 Secreting Macrophages Is Associated With Antitumor Immunity And Response To Therapy In Ovarian Cancer Subtypes, Laura Ardighieri, William Vermi, Et Al

Open Access Publications

Ovarian carcinomas (OCs) are poorly immunogenic and immune checkpoint inhibitors (ICIs) have offered a modest benefit. In this study, high CD3

Outcome After Acute Ischemic Stroke Is Linked To Sex-Specific Lesion Patterns, Anna K. Bonkhoff, Laura Heitsch, Chia-Ling Phuah, Et Al

Open Access Publications

No abstract provided.

Untargeted Metabolomics And Infrared Ion Spectroscopy Identify Biomarkers For Pyridoxine-Dependent Epilepsy, Udo Fh Engelke, Laura A Jansen, Et Al

Open Access Publications

BackgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.MethodsWe combined the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy to discover …

Dysregulation Of Mannose-6-Phosphate-Dependent Cholesterol Homeostasis In Acinar Cells Mediates Pancreatitis, Olga A Mareninova, Yan Xie, Nicholas O Davidson, Et Al

Open Access Publications

Disordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake. We found similar dysregulation of acinar cell cholesterol, and a decrease in GNPTAB levels, in both WT experimental pancreatitis and human disease. The …

Neurofibrillary Tau Depositions Emerge With Subthreshold Cerebral Beta-Amyloidosis In Down Syndrome, Matthew D Zammit, Dana L Tudorascu, Charles M Laymon, Sigan L Hartley, Paul A Ellison, Shahid H Zaman, Beau M Ances, Sterling C Johnson, Charles K Stone, Marwan N Sabbagh, Chester A Mathis, William E Klunk, Ann D Cohen, Benjamin L Handen, Bradley T Christian

Open Access Publications

INTRODUCTION: Adults with Down syndrome are genetically predisposed to develop Alzheimer's disease and accumulate beta-amyloid plaques (Aβ) early in life. While Aβ has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aβ burden.

METHODS: A total of 161 adults with Down syndrome (mean age = 39.2 (8.50) years) and 40 healthy, non-Down syndrome sibling controls (43.2 (12.6) years) underwent T1w-MRI, [C-11]PiB and [F-18]AV-1451 PET scans. PET images were converted to units of standardized uptake …

White Matter Integrity Of Contralesional And Transcallosal Tracts May Predict Response To Upper Limb Task-Specific Training In Chronic Stroke, Daniela J S Mattos, Jerrel Rutlin, Xin Hong, Kristina Zinn, Joshua S Shimony, Alexandre R Carter

Open Access Publications

OBJECTIVE: To investigate white matter (WM) plasticity induced by intensive upper limb (UL) task specific training (TST) in chronic stroke.

METHODS: Diffusion tensor imaging data and UL function measured by the Action Research Arm Test (ARAT) were collected in 30 individuals with chronic stroke prior to and after intensive TST. ANOVAs tested the effects of training on the entire sample and on the Responders [ΔARAT ≥ 5.8, N = 13] and Non-Responders [ΔARAT < 5.8, N = 17] groups. Baseline fractional anisotropy (FA) values were correlated with ARATpost TST controlling for baseline ARAT and age to identify voxels predictive of response to TST.

RESULTS: While ARAT scores increased following training (p < 0.0001), FA changes within major WM tracts were not significant at p < 0.05. In the Responder group, larger baseline FA of both contralesional (CL) and transcallosal tracts predicted larger ARAT scores post-TST. Subcortical lesions and more severe damage to transcallosal tracts were more pronounced in the Non-Responder than in the Responder group.

CONCLUSIONS: The motor improvements post-TST in the Responder group may reflect the engagement of interhemispheric processes not available to …

Listeria Exploits Ifitm3 To Suppress Antibacterial Activity In Phagocytes, Joel M. J. Tan, Michael S. Diamond, Et Al

Open Access Publications

No abstract provided.