Digital Commons Network^™

Disruption Of The Cerebrospinal Fluid-Plasma Protein Balance In Cognitive Impairment And Aging, Amelia Farinas, Daniel Western, Jigyasha Timsina, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium. We identified proteins with correlated CSF and plasma levels that are produced primarily outside the brain and are enriched for structural domains that may enable their …

Tau Pet Positivity In Individuals With And Without Cognitive Impairment Varies With Age, Amyloid-Β Status, Apoe Genotype And Sex, Rik Ossenkoppele, Tammy L S Benzinger, Et Al.

2020-Current year OA Pubs

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU …

The Microrna Mir-30a Blocks Adipose Tissue Fibrosis Accumulation In Obesity, Pradip K Saha, Robert Sharp, Aaron R. Cox, Rabie Habib, Michael J. Bolt, Jessica B. Felix, Claudia E. Ramirez Bustamante, Xin Li, Sung Yun Jung, Kang Ho Kim, Kai Sun, Huaizhu Wu, Samuel Klein, Sean M. Hartig

2020-Current year OA Pubs

White adipose tissue (WAT) fibrosis occurring in obesity contributes to the inflammatory and metabolic comorbidities of insulin resistance and type 2 diabetes, yet the mechanisms involved remain poorly understood. Here, we report a role for the broadly conserved miRNA miR-30a as a regulator of WAT fibrosis and systemic glucose metabolism. Mice modified to express miR-30a at elevated levels in adipose tissues maintain insulin sensitivity coupled with reduced fatty liver disease when fed a high-fat diet. These effects were attributable to cell-autonomous functions of miR-30a that potently increase expression of adipocyte-specific genes. Proteomic screening revealed miR-30a limits profibrotic programs in subcutaneous …

Active Dna Demethylation Upstream Of Rod-Photoreceptor Fate Determination Is Required For Retinal Development, Ismael Hernández-Núñez, Alaina Urman, Xiaodong Zhang, William Jacobs, Christy Hoffmann, Ellen G. Harding, Shiming Chen, Meelad M. Dawlaty, Philip A. Ruzycki, John R. Edwards, Brian S. Clark

2020-Current year OA Pubs

Retinal cell fate specification from multipotent retinal progenitors is governed by dynamic changes in chromatin structure and gene expression. Methylation at cytosines in DNA (5mC) is actively regulated for proper control of gene expression and chromatin architecture. Numerous genes display active DNA demethylation across retinal development; a process that requires oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and is controlled by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. Using an allelic series of conditional TET enzyme mutants in mice, we determine that DNA demethylation is required upstream of NRL and NR2E3 expression for the establishment of rod-photoreceptor fate. Using histological, behavioral, …

Autophagy Regulates Müller Glial Cell Inflammatory Activation, Teresa A Doggett, Zhenqing Zhou, Sohini Rebba, Jacqueline Unsinger, Philip A Ruzycki, Thomas A Ferguson

2020-Current year OA Pubs

PURPOSE: We tested whether Müller cells utilize autophagy to support immune privilege in the eye.

METHODS: The essential autophagy gene Atg5 was deleted in retinal Müller cells. Inflammation was induced by intravitreal injection of lipopolysaccharide (LPS) that was monitored by hematoxylin and eosin (H&E) staining, immunofluorescent confocal microscopy, and flow cytometry. Single-cell RNA sequencing was performed on retinal Müller cells isolated from control and Atg5-deficient mice. Markers of Müller cell gliosis were assessed, and cytokine production in the eye was measured. Small interfering RNA knockdown techniques were used to examine LPS-induced inflammatory pathways in culture.

RESULTS: We observed increased and …

Longer Scans Boost Prediction And Cut Costs In Brain-Wide Association Studies, Leon Qi Rong Ooi, Scott Marek, Nico U F Dosenbach, Timothy O Laumann, Evan M Gordon, Et Al.

2020-Current year OA Pubs

A pervasive dilemma in brain-wide association studies

High-Density Lipoprotein-Associated Cholesterol Abnormalities In A Clinical Outcomes Study Of Dysferlin-Deficient Limb-Girdle Muscular Dystrophy Type R2, Zoe White, Alan Pestronk, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limb-girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, DYSF. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.

METHODS: Cross-sectional circulating total cholesterol (CHOL), high-density lipoprotein-associated …

Sex-Related Variability In The Perception Of Symptoms Associated With Common Otolaryngologic Complaints, Sabrina K Wagner, Jakob L Fischer, Alvaro Navarro, Lily Trinh, Waleed M Abuzeid, Ian M Humphreys, Nadeem A Akbar, Sharan Shah, Jivianne T Lee, Tara Wu, John S Schneider, Edward D Mccoul, Charles A Riley, Anthony M Tolisano

2020-Current year OA Pubs

OBJECTIVE: To assess the differences in the symptoms associated with common otolaryngology complaints between male and female patients.

METHODS: Between June 2020 and July 2023, a multi-institutional cross-sectional study was performed at six tertiary academic otolaryngology practices using semantics-based questionnaires to assess the symptoms patients associate with the complaints of sinus infection, reflux, congestion, and dizziness. Patients selected symptoms from lists of proposed terms to describe the various conditions. The primary outcome measure was sex-related differences in respondent symptom selection.

RESULTS: Four separate questionnaires were completed by a total of 1495 patients (46.0% male, 54.0% female). Female patients more often …

Association Between Nt-Probnp Changes And Clinical Outcomes In Paediatric Patients With Heart Failure: Insights From Panorama-Hf And Paradigm-Hf, Robert Shaddy, Charles Canter, Et Al.

2020-Current year OA Pubs

AIMS: The PANORAMA-HF trial demonstrated significant N-terminal pro-B-type natriuretic peptide (NT-proBNP) reductions in paediatric patients with left ventricular systolic dysfunction with sacubitril/valsartan or enalapril treatment over 52 weeks. This post hoc analysis aims to correlate changes in NT-proBNP levels with clinical outcomes in PANORAMA-HF patients receiving either sacubitril/valsartan or enalapril. Additionally, NT-proBNP reductions in the paediatric population were compared with a subset of adult heart failure with reduced ejection fraction (HFrEF) patients from the PARADIGM-HF trial.

METHODS AND RESULTS: This post hoc analysis utilized data from Part 2 of the PANORAMA-HF trial. Associations between baseline NT-proBNP levels, changes post-baseline and …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

METHODS: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

RESULTS: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

Formation Control Between Leader And Migratory Follower Tissues Allows Coordinated Growth, Toru Kawanishi, Takamichi Sushida, Tony Y-C Tsai, Hiroyuki Takeda, Sean G Megason

2020-Current year OA Pubs

Coordinated growth of multiple tissues is fundamental to shaping our body, but the underlying mechanisms remain underexplored. In zebrafish embryos, midline tissues composed of the notochord, floorplate, and hypochord elongate synchronously with their lengths aligned. We show that floorplate and hypochord cells collectively migrate posteriorly along the nascent notochord extracellular matrix as it extends posteriorly, maintaining the tripartite configuration. Fibroblast growth factor-mediated migration in a spatially graded manner causes cell stretching, which triggers Yap-dependent proliferation and controls floorplate and hypochord growth. Supported by mathematical modeling, we further suggest that their growth is fine-tuned by mechanical tethering to the notochord via …

Human Thalamocortical Structural Connectivity Develops In Line With A Hierarchical Axis Of Cortical Plasticity, Valerie J Sydnor, Deanna M Barch, Et Al.

2020-Current year OA Pubs

Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain's capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8-23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in …

The Importance Of Imperfect Pre-Clinical Models In Adolescent Idiopathic Scoliosis, Diane S Sepich, Ryan S Gray, Nadav Ahituv, Christina A Gurnett, Jonathan J Rios, Lila Solnica-Krezel, Carol A Wise

2020-Current year OA Pubs

Adolescent idiopathic scoliosis (AIS) is a twisting spinal deformity that occurs in otherwise healthy children at the time of rapid pre-pubescent growth. AIS affects ∼3% of children worldwide and is the most common musculoskeletal diagnosis in pediatric populations, posing a significant physiological, psychosocial and financial burden to patients. Genetic predisposition is a clear and major contributor to AIS, and insights from genomic discoveries are inspiring translational studies ultimately aimed at developing novel diagnostics and therapies. Pre-clinical animal models of AIS are now essential to validate human genetic findings, understand gene-by-environment interactions, and speed etiologic and therapeutic discovery. In this Perspective, …

Advanced Quantification Pipeline Reveals New Spatial And Temporal Tumor Characteristics In Preclinical Multiple Myeloma, Zhixin Sun, Jacqueline M Godbe, Alexander Zheleznyak, Brad Manion, Junhao Hu, Julie L Prior, Kathleen Duncan, Ulugbek S Kamilov, Monica Shokeen

2020-Current year OA Pubs

BACKGROUND: Radiological imaging plays an indispensable role in both preclinical and clinical studies of multiple myeloma (MM). However, manual quantification in longitudinal small animal PET/CT is limited by annotator bias, signal artifacts from urinary/fecal excretion, and voxel misalignment due to non-rigid registration. To address these challenges and improve characterization of tumor biology, we developed a semi-automated PET/CT quantification pipeline targeting defined regions of interest (ROIs) within the bone marrow-rich mouse skeleton, achieving sub-organ spatial resolution, including in anatomically complex sites such as the pelvis. We applied this MM-specific preclinical pipeline to analyze tumor distribution in a longitudinal molecular PET study …

Effects Of The Gut Microbiota On Placental Angiogenesis And Intrauterine Growth In Gnotobiotic Mice, Reyan Coskun, Zenan L Chang, Athziri Marcial Rodríguez, Haoxin Liu, Jiye Cheng, Yael Alippe, Michael S Diamond, Jeffrey I Gordon

2020-Current year OA Pubs

Environmental causes of intrauterine growth restriction (IUGR) remain poorly characterized. Here, we compare germ-free (GF) and conventionally raised (CONV-R) mice to assess the effects of the gut microbiota on placental/fetal development at embryonic day (E)11.5 (end of placentation) and E17.5 (near term). Pregnancy- and microbiota-associated changes in gene expression occur along the gut, including those related to angiogenesis, while bacterial composition and fermentation activity remain stable. Placental weights at E11.5 and fetal weights at E17.5 are significantly reduced in GF animals. Compared to CONV-R dams, the GF maternal decidua exhibits similar vascular histomorphometric features at E11.5 and E17.5, and numbers …

The Biophysical Basis For Karyopherin-Dependent Ebola Virus Vp24 Nuclear Transport, Junjie Zhao, Bojie Zhang, Olivia Vogel, Benjamin W Walker, Leonard W Ma, Nicole D Wagner, Christopher F Basler, Daisy W Leung, Michael L Gross, Gaya K Amarasinghe

2020-Current year OA Pubs

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription. However, the molecular interactions of eVP24-KPNA5 binding that lead to the nuclear localization of eVP24 remain poorly characterized. Here, we show that trafficking of eVP24 …

Single-Cell Transcriptomics Of Ventral Forebrain Progenitors Identifies Evf2 Enhancer Lncrna-Enhancer Gene Guidance Through Direct Rna Binding And Rnp Recruitment Domains, Edward Li, Abhijit Chakraborty, Sara J Kohtz, Ivelisse Cajigas, Laura Hinojosa-Gonzalez, Fion Shiau, Ryan Bertossi, Robert J Vassar, Jack A Kessler, Ferhat Ay, Brian S Clark, Jhumku D Kohtz

2020-Current year OA Pubs

During mouse embryonic brain development, the Evf2 ultraconserved enhancer (UCE) lncRNA guides the Dlx5/6UCE to ~129 sites across chr6. However, previous work identified only 4 transcriptionally regulated targets associated with Evf2-Dlx5/6UCE-gene guidance, raising questions about the significance of Evf2-regulated Dlx5/6UCE-gene interactions. Here, single-cell transcriptomics reveal far greater alignment between Evf2-Dlx5/6UCE-gene guidance and transcriptional regulation than previously reported. Evf2 divides chr6 into short-range ( < 10 Mb distant), activated genes, and long/super-long-range (10-129 Mb distant), repressed genes, identifying seizure regulating genes in the embryonic subventricular zone that predict adult phenotypes. Evf2-regulated Dlx5/6UCE-gene distances and directions (closer to or further from gene targets) can be decoupled from gene target transcriptional effects. Evf2 regulates Evf2-ribonucleoprotein (RNP) binding in a combinatorial manner to key regulatory sites, including chr6 Evf2-Dlx5/6UCE-gene guided sites, Evf1/2 RNA-directly bound sites (RBSs), and inter-chromosomal HiC looping interactions. RBSs divide chromosomes into multi-megabase domains enriched for Evf2-regulated RNP recruitment, transcription factor motifs, and HiC looping interactions. Together with Evf2-controlled homeobox motif recognition at Evf2-RNP recruitment sites and transcription factor motif enrichment in RBSs with DNA identity, this work supports direct roles for Evf2 in enhancer-gene guidance and transcriptional regulation, with the potential for both site-specific and chromosomal domain specific RNP recruitment.

Replication Of Sensor-Based Categorization Of Upper-Limb Performance In Daily Life In People Post Stroke And Generalizability To Other Populations, Chelsea E Macpherson, Marghuretta D Bland, Christine Gordon, Allison E Miller, Caitlin Newman, Carey L Holleran, Christopher J Dy, Lindsay Peterson, Keith R Lohse, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Wearable movement sensors can measure upper limb (UL) activity, but single variables may not capture the full picture. This study aimed to replicate prior work identifying five multivariate categories of UL activity performance in people with stroke and controls and expand those findings to other UL conditions.

METHODS: Demographic, self-report, and wearable sensor-based UL activity performance variables were collected from 324 participants (stroke

RESULTS: Two PCs explained 70-90% variance: PC1 (overall UL activity performance) and PC2 (preferred-limb use). A five-variable, five-cluster model was optimal across samples. In comparison to clusters, two PCs and individual accelerometry variables showed higher convergent …

U-Rich Elements Drive Pervasive Cryptic Splicing In 3' Utr Massively Parallel Reporter Assays, Khoa Dao, Courtney F Jungers, Sergej Djuranovic, Anthony M Mustoe

2020-Current year OA Pubs

Untranslated RNA sequences play essential roles in orchestrating gene expression. However, the sequence codes and mechanisms underpinning post-transcriptional regulation remain incompletely understood. Here, we revisit the finding from a prior massively parallel reporter assay (MPRA) that AU-rich elements in 3' untranslated regions (3' UTRs) can drive upregulation or downregulation of mRNA expression depending on 3' UTR context. We unexpectedly discover that this variable regulation arises from widespread cryptic splicing, predominately from an unannotated splice donor in the coding sequence of GFP to diverse acceptor sites in reporter 3' UTRs. Splicing is activated by U-rich sequences, which function as potent position-dependent …

Phase 1b/2 Study Evaluating Safety, Efficacy And Immune Effects Of Tlr9 Agonist Cavrotolimod With Anti-Pd-1 Antibodies Among Patients With Advanced Solid Tumors, Mohammed M Milhem, George Ansstas, Et Al.

2020-Current year OA Pubs

BACKGROUND: There is an unmet need for novel immunotherapies to overcome immune evasion in patients with advanced skin cancers resistant to programmed death (PD)-1 / PD-ligand 1 (PD-L1) blockade. Cavrotolimod is a novel spherical nucleic acid configuration of a toll-like receptor 9 agonist oligonucleotide, designed to trigger innate and adaptive immune responses to tumors.

PATIENTS AND METHODS: The safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of intratumoral cavrotolimod, first dosed alone and then in combination with anti-PD-1 antibodies (pembrolizumab or cemiplimab), were assessed in a combined Phase 1b/2 dose escalation/dose expansion study in patients with advanced skin cancers, including melanoma, Merkel …

Macrophage-T Cell Interactions Promote Slamf1 Expression For Enhanced Tb Defense, G V R Krishna Prasad, Steven J Grigsby, Gideon A Erkenswick, Cynthia Portal-Celhay, Ekansh Mittal, Guozhe Yang, Samuel M Fallon, Fengyixin Chen, Thais Klevorn, Neharika Jain, Yuanyuan Li, Makedonka Mitreva, Amanda J Martinot, Joel D Ernst, Jennifer A Philips

2020-Current year OA Pubs

CD4+ T cells are crucial for protective immunity to intracellular pathogens. In addition to secreting cytokines, CD4+ T cells promote control of Mycobacterium tuberculosis infection through cognate interactions with macrophages, but the mechanism has been unclear. Here, we show that SLAMF1/CD150 is highly and uniquely induced in macrophages by antigen-specific interactions with CD4+ T cells. In macrophages, SLAMF1 enhances the generation of reactive oxygen species and restricts Mtb replication. Mtb-infection of mice promotes SLAMF1 expression specifically on infected macrophages, not uninfected bystanders. SLAMF1 expression depends on adaptive immunity and also autophagy. Moreover, Slamf1

Sepsis Restructures The Mitochondrial Calcium Uniporter Complex In The Lymphoid Tissues Of Mice And Humans, Xianghong Zhang, Jianguo Lin, Baobo Zou, Jack R Killinger, Andrew C Sayce, Thiagarajan Meyyappan, Zeyu Xiong, Melanie J Scott, Janet S Lee, Matthew R Rosengart

2020-Current year OA Pubs

Survivors of sepsis suffer from an elevated risk of premature death that is not explained by a higher burden of chronic diseases prior to the infection. Nearly 1 out of 4 survivors have persistent elevations of inflammation biomarkers, such as interleukin (IL) 6. These observations suggest that sepsis imparts durable changes to organismal biology. Eukaryotic life depends upon ATP and calcium (Ca

Cdc1s Promote Atherosclerosis Via Local Immunity And Are Targetable For Therapy, Miguel Galán, Suin Jo, Tian-Tian Liu, Kenneth M. Murphy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Atherosclerosis is characterized by immune cell accumulation in the arterial wall and adaptive CD4

METHODS: We tested atherosclerosis in

RESULTS: Expansion of DCs in

CONCLUSIONS: Using state-of-the-art strategies, our results establish that cDC1s have a proatherogenic role in atherosclerosis by boosting CD4

Electrophysiological Characterization Of Sex-Dependent Hypnosis By An Endogenous Neuroactive Steroid Epipregnanolone, Tamara Timic Stamenic, Ian Coulter, Douglas F Covey, Slobodan M Todorovic

2020-Current year OA Pubs

Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral …

Identification Of Functional Non-Coding Variants Associated With Orofacial Cleft, Priyanka Kumari, Ryan Z Friedman, Michael A White, Barak A Cohen, Et Al.

2020-Current year OA Pubs

Oral facial cleft (OFC) comprises cleft lip with or without cleft palate (CL/P) or cleft palate only. Genome wide association studies (GWAS) of isolated OFC have identified common single nucleotide polymorphisms (SNPs) in many genomic loci where the presumed effector gene (for example, IRF6 in the 1q32 locus) is expressed in embryonic oral epithelium. To identify candidates for functional SNPs at eight such loci we conduct a massively parallel reporter assay in a fetal oral epithelial cell line, revealing SNPs with allele-specific effects on enhancer activity. We filter these SNPs against chromatin-mark evidence of enhancers and test a subset in …

V2b Neurons Act Via Multiple Targets To Produce In Phase Inhibition During Locomotion, Mohini Sengupta, Alaina Bertram, Shuyu Iris Zhu, Geoffrey J Goodhill, Martha W Bagnall

2020-Current year OA Pubs

Spinal interneurons shape motor neuron activity. Gata3

Cryo-Em Structures Of A Pentameric Ligand-Gated Ion Channel In Liposomes, Vikram Dalal, Brandon K Tan, Hanrui Xu, Wayland W L Cheng

2020-Current year OA Pubs

Detergents and lipid nanodiscs affect the cryo-EM structures of pentameric ligand-gated ion channels (pLGICs) including ELIC. To determine the structure of a pLGIC in a membrane environment that supports ion channel function, we performed single particle cryo-EM of ELIC in liposomes. ELIC activation and desensitization were confirmed in liposomes with a stopped-flow thallium flux assay. Using WT ELIC and a non-desensitizing mutant (ELIC5), we captured resting, activated, and desensitized structures at high resolution. In the desensitized structure, the ion conduction pore has a constriction at the 9' leucine of the pore-lining M2 helix, indicating that 9' is the desensitization gate …

Integrated Genomic Analysis Of Nf1-Associated Peripheral Nerve Sheath Tumors: An Updated Biorepository Dataset, Jineta Banerjee, Yang Lyu, Kuangying Yang, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous condition that predisposes to the development of peripheral nerve sheath tumors (PNST) including cutaneous neurofibromas (CNF), plexiform neurofibromas (PNF), atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), and malignant peripheral nerve sheath tumors (MPNST). The Johns Hopkins NF1 biospecimen repository promotes the successful advancement of therapeutic developments for NF1-associated PNST through acquisition and genomic analysis of human tumor specimens. RNA sequencing (RNAseq) and whole exome sequencing (WES) data were generated from 73 and 114 primary human tumor samples, respectively. These pre-processed data, standardized for immediate computational analysis, are accessible through the NF …

Self-Other Generalisation Shapes Social Interaction And Is Disrupted In Borderline Personality Disorder, Joseph M Barnby, Jen Nguyen, Julia Griem, Magdalena Wloszek, Henry Burgess, Linda J Richards, Jessica Kingston, Gavin Cooper, P Read Montague, Peter Dayan, Tobias Nolte, Peter Fonagy, London Personality And Mood Disorders Consortium

2020-Current year OA Pubs

Generalising information from ourselves to others, and others to ourselves allows for both a dependable source of navigation and adaptability in interpersonal exchange. Disturbances to social development in sensitive periods can cause enduring and distressing damage to lasting healthy relationships. However, identifying the mechanisms of healthy exchange has been difficult. We introduce a theory of self-other generalisation tested with data from a three-phase social value orientation task - the Intentions Game. We involved humans with (

Ablation Of The Evolutionarily Acquired Functions Of The Atp1b4 Gene Increases Metabolic Capacity And Reduces Obesity, Nikolai N Modyanov, Lucia Russo, Sumona Ghosh Lester, Tamara R Castañeda, Himangi G Marathe, Larisa V Fedorova, Raymond E Bourey, Sonia M Najjar, Ivana L De La Serna

2020-Current year OA Pubs

In placental mammals, the co-option of vertebrate orthologous