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Cockayne Syndrome: The Many Challenges And Approaches To Understand A Multifaceted Disease, Alexandre Teixeira Vessoni, Camila Chaves Coelho Guerra, Gustavo Satoru Kajitani, Livia Luz Souza Nascimento, Camila Carrião Machado Garcia

Open Access Publications

The striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS …

The Genetic Architecture Of Sporadic And Multiple Consecutive Miscarriage, Triin Laisk, Avinash Ramu, Donald F. Conrad, Et Al.

Open Access Publications

No abstract provided.

Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-Methylpyrimidine-2, 4-Diamine (Th287): A Potential Radiotracer For Measuring And Imaging Mth1, Huaping Chen, Sadia Afrin, Yingqiu Guo, Wenhua Chu, Tammie L S Benzinger, Buck E Rogers, Joel R Garbow, Joel S Perlmutter, Dong Zhou, Jinbin Xu

Open Access Publications

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [

Chemical Mutagenesis Of A Gpcr Ligand: Detoxifying “Inflammo-Attraction” To Direct Therapeutic Stem Cell Migration, Jean-Pyo Lee, Edward B. Han, Et Al.

Open Access Publications

No abstract provided.

Social Jetlag And Prostate Cancer Incidence In Alberta's Tomorrow Project: A Prospective Cohort Study, Liang Hu, Andrew Harper, Emily Heer, Jessica Mcneil, Chao Cao, Yikyung Park, Kevin Martell, Geoffrey Gotto, Grace Shen-Tu, Cheryl Peters, Darren Brenner, Lin Yang

Open Access Publications

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta's Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-<1 h (from 0 to anything smaller than 1), 1-<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (

The Effect Of Smoking During Pregnancy On Severity And Directionality Of Externalizing And Internalizing Symptoms: A Genetically Informed Approach, Mikael O Ekblad, Kristine Marceau, Emily Rolan, Rohan H C Palmer, Alexandre Todorov, Andrew C Heath, Valerie S Knopik

Open Access Publications

The objective was to examine the association between maternal smoking during pregnancy (SDP) and (I) severity and (II) directionality of externalizing and internalizing symptoms in a sample of sibling pairs while rigorously controlling for familial confounds. The Missouri Mothers and Their Children Study is a family study (N = 173 families) with sibling pairs (aged 7 to 16 years) who are discordant for exposure to SDP. This sibling comparison study is designed to disentangle the effects of SDP from familial confounds. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount). …

Relations Between Sensory Responsiveness And Features Of Autism In Children, Jacob I Feldman, Margaret Cassidy, Yupeng Liu, Anne V Kirby, Mark T Wallace, Tiffany G Woynaroski

Open Access Publications

Autism is a neurodevelopmental condition defined by differences in social communication and by the presence of restricted and repetitive patterns of behavior, interests, and activities (RRBs). Individuals with autism also commonly present with atypical patterns of sensory responsiveness (i.e., hyporesponsiveness, hyperresponsiveness, and sensory seeking), which are theorized to produce cascading effects across other domains of development. The purpose of this study was to examine differences in sensory responsiveness in children with and without autism (ages 8-18 years), as well as relations between patterns of sensory responsiveness and core and related features of autism. Participants were 50 children with autism and …

Pd-L1 Blockade In Combination With Inhibition Of Mapk Oncogenic Signaling In Patients With Advanced Melanoma, Antoni Ribas, Alain Algazi, Paolo A. Ascierto, Marcus O. Butler, Sunandana Chandra, Michael Gordon, Leonel Hernandez-Aya, Donald Lawrence, Jose Lutzky, Wilson H. Miller Jr., Katie M. Campbell, Bruno Delafont, Shannon Marshall, Nancy Mueller, Caroline Robert

Open Access Publications

No abstract provided.

Novel Multimodal Molecular Imaging Of Vitamin H (Biotin) Transporter Activity In The Murine Placenta, Ben Eliezer Noam, Lysenko Marina, Biton E. Inbal, Golani Ofra, Bartels L. Jennifer, Fernandez R. Solana, Aweda A. Tolulope, Clanton A. Nicholas, Beacham Rebecca, Lapi E. Suzanne, Garbow R. Joel, Neeman Michal

Open Access Publications

No abstract provided.

A Matricellular Protein Fibulin-4 Is Essential For The Activation Of Lysyl Oxidase, Kazuo Noda, Kaori Kitagawa, Takao Miki, Masahito Horiguchi, Tomoya O Akama, Takako Taniguchi, Hisaaki Taniguchi, Kazuaki Takahashi, Yasumitsu Ogra, Robert P Mecham, Masahiko Terajima, Mitsuo Yamauchi, Tomoyuki Nakamura

Open Access Publications

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (

Distinct Inflammatory Profiles Distinguish Covid-19 From Influenza With Limited Contributions From Cytokine Storm, Philip A Mudd, Jackson S Turner, Daniel Reynolds, Diane Bender, Adrianus C M Boon, Stacey L House, Kenneth E Remy, Richard S Hotchkiss, Rachel M Presti, Jane A O'Halloran, William G Powderly, Ali H Ellebedy, Et Al

Open Access Publications

We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, …

Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz

Open Access Publications

No abstract provided.

Natural Bladder Flling Alters Resting Brain Function At Multiple Spatial Scales: A Proof‑Of‑Concept Mapp Network Neuroimaging Study, Ishtiaq Mawla, Henry Lai, Gerald Andriole, Et Al.

Open Access Publications

No abstract provided.

Termini Restraining Of Small Membrane Proteins Enables Structure Determination At Near-Atomic Resolution, Shixuan Liu, Shuang Li, Yihu Yang, Weikai Li

Open Access Publications

Small membrane proteins are difficult targets for structural characterization. Here, we stabilize their folding by restraining their amino and carboxyl termini with associable protein entities, exemplified by the two halves of a superfolder GFP. The termini-restrained proteins are functional and show improved stability during overexpression and purification. The reassembled GFP provides a versatile scaffold for membrane protein crystallization, enables diffraction to atomic resolution, and facilitates crystal identification, phase determination, and density modification. This strategy gives rise to 14 new structures of five vertebrate proteins from distinct functional families, bringing a substantial expansion to the structural database of small membrane proteins. …

Comparing Cortical Signatures Of Atrophy Between Late-Onset And Autosomal Dominant Alzheimer Disease, Aylin Dincer, Brian A Gordon, Sarah J Keefe, Shaney Flores, Nicole S Mckay, Angela M Paulick, Rebecca L Feldman, Russ C Hornbeck, Beau M Ances, Nelly Joseph-Mathurin, Celeste M Karch, Eric M Mcdade, Richard J Perrin, Cyrus Raji, Qing Wang, Chengjie Xiong, John C Morris, Randall J Bateman, Tammie L S Benzinger, Et Al

Open Access Publications

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes …

Pathophysiological Consequences Of Katp Channel Overactivity And Pharmacological Response To Glibenclamide In Skeletal Muscle Of A Murine Model Of Cantù Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Antonietta Mele, Giulia Maria Camerino, Francesco Alfredo Zito, Girolamo Ranieri, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

Cantù syndrome (CS) arises from mutations in

Exploring Differences In The Role Of Hospitalization On Weight Gain Based On Treatment Type From Randomized Clinical Trials For Adolescent Anorexia Nervosa, Nandini Datta, Brittany E Matheson, Daniel Le Grange, Harry A Brandt, Blake Woodside, Katherine A Halmi, Denise E Wilfley, James D Lock

Open Access Publications

No abstract provided.

Documenting Social Media Engagement As Scholarship: A New Model For Assessing Academic Accomplishment For The Health Professions, Kimberly D Acquaviva, Rakhee K Bhayani, Et Al

Open Access Publications

BACKGROUND: The traditional model of promotion and tenure in the health professions relies heavily on formal scholarship through teaching, research, and service. Institutions consider how much weight to give activities in each of these areas and determine a threshold for advancement. With the emergence of social media, scholars can engage wider audiences in creative ways and have a broader impact. Conventional metrics like the h-index do not account for social media impact. Social media engagement is poorly represented in most curricula vitae (CV) and therefore is undervalued in promotion and tenure reviews.

OBJECTIVE: The objective was to develop crowdsourced guidelines …

Fetal Cortical Plate Segmentation Using Fully Convolutional Networks With Multiple Plane Aggregation, Jinwoo Hong, Hyuk Jin Yun, Gilsoon Park, Seonggyu Kim, Cynthia T Laurentys, Leticia C Siqueira, Tomo Tarui, Caitlin K Rollins, Cynthia M Ortinau, P Ellen Grant, Jong-Min Lee, Kiho Im

Open Access Publications

Fetal magnetic resonance imaging (MRI) has the potential to advance our understanding of human brain development by providing quantitative information of cortical plate (CP) development

From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al.

Open Access Publications

No abstract provided.

Fenofibrate Reduces The Severity Of Neuroretinopathy In A Type 2 Model Of Diabetes Without Inducing Peroxisome Proliferator-Activated Receptor Alpha-Dependent Retinal Gene Expression, Jennifer M Enright, Sheng Zhang, Christina Thebeau, Emily Siebert, Alexander Jin, Veda Gadiraju, Xiaodong Zhang, Shiming Chen, Clay F Semenkovich, Rithwick Rajagopal

Open Access Publications

Fenofibrate slows the progression of clinical diabetic retinopathy (DR), but its mechanism of action in the retina remains unclear. Fenofibrate is a known agonist of peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor critical for regulating metabolism, inflammation and oxidative stress. Using a DR mouse model,

Neutrophil L-Plastin Controls Ocular Paucibacteriality And Susceptibility To Keratitis, Xiaoxiao Lu, Abirami Kugadas, Kirsten Smith-Page, Jeffrey Lamb, Tiffany Lin, Yusha Ru, Sharon Celeste Morley, Raina Fichorova, Sharad K Mittal, Sunil K Chauhan, Sejiro Littleton, Daniel Saban, Mihaela Gadjeva

Open Access Publications

Why ocular mucosa is paucibacterial is unknown. Many different mechanisms have been suggested but the comprehensive experimental studies are sparse. We found that a deficiency in L-plastin (LCP1), an actin bundling protein, resulted in an ocular commensal overgrowth, characterized with increased presence of conjunctival

Immunomodulatory Roles Of Polysaccharide Capsules In The Intestine, Samantha A Hsieh, Paul M Allen

Open Access Publications

The interplay between the immune system and the microbiota in the human intestine dictates states of health vs. disease. Polysaccharide capsules are critical elements of bacteria that protect bacteria against environmental and host factors, including the host immune system. This review summarizes the mechanisms by which polysaccharide capsules from commensal and pathogenic bacteria in the gut microbiota modulate the innate and adaptive immune systems in the intestine. A deeper understanding of the roles of polysaccharide capsules in microbiota-immune interactions will provide a basis to harness their therapeutic potential to advance human health.

Lipin-1 Contributes To Il-4 Mediated Macrophage Polarization, Sunitha Chandran, Robert M Schilke, Cassidy M R Blackburn, Aila Yurochko, Rusella Mirza, Rona S Scott, Brian N Finck, Matthew D Woolard

Open Access Publications

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 …

Multiple Network Disconnection In Anosognosia For Hemiplegia, Elena Monai, Francesca Bernocchi, Marta Bisio, Antonio Luigi Bisogno, Alessandro Salvalaggio, Maurizio Corbetta

Open Access Publications

Anosognosia for hemiplegia (AHP) is a complex syndrome whose neural correlates are still under investigation. One hypothesis, mainly based on lesion mapping studies, is that AHP reflects a breakdown of neural systems of the right hemisphere involved in motor function. However, more recent theories have suggested that AHP may represent a disorder of cognitive systems involved in belief updating, self-referential or body processing. Two recent studies, using a method to estimate the degree of white matter disconnection from lesions, have indeed shown that patients with AHP suffer from damage of several long-range white matter pathways in association cortex. Here, we …

Development Of Volumetric Independent Dose Calculation System For Verification Of The Treatment Plan In Image-Guided Adaptive Brachytherapy, Sang-Won Kang, Jin-Beom Chung, Kyeong-Hyeon Kim, Ji-Yeon Park, Hae-Jin Park, Woong Cho, Sven Olberg, Tae Suk Suh, Justin C Park

Open Access Publications

No abstract provided.

Sequencing-Based Measurable Residual Disease Testing In Acute Myeloid Leukemia, Jennifer M Yoest, Cara Lunn Shirai, Eric J Duncavage

Open Access Publications

Next generation sequencing (NGS) methods have allowed for unprecedented genomic characterization of acute myeloid leukemia (AML) over the last several years. Further advances in NGS-based methods including error correction using unique molecular identifiers (UMIs) have more recently enabled the use of NGS-based measurable residual disease (MRD) detection. This review focuses on the use of NGS-based MRD detection in AML, including basic methodologies and clinical applications.

Dopamine Buffering Capacity Imaging: A Pharmacodynamic Fmri Method For Staging Parkinson Disease, Kevin J Black, Haley K Acevedo, Jonathan M Koller

Open Access Publications

We propose a novel pharmacological fMRI (phMRI) method for objectively quantifying disease severity in Parkinson disease (PD). It is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled based on clinical effects, but clinical measurements are influenced by confounding factors. The new method proposes to measure the effect objectively based on the timing of the known response of several brain regions to exogenous levodopa. Such responses are robust …

Motor Unit Discharge Variability Is Increased In Mild-To-Moderate Parkinson's Disease, Jessica M Wilson, Christopher K Thompson, Laura Miller Mcpherson, Cindy Zadikoff, C J Heckman, Colum D Mackinnon

Open Access Publications

Individuals with Parkinson's disease (PD) demonstrate deficits in muscle activation such as decreased amplitude and inappropriate bursting. There is evidence that some of these disturbances are more pronounced in extensor vs. flexor muscles. Surface EMG has been used widely to quantify muscle activation deficits in PD, but analysis of discharge of the underlying motor units may provide greater insight and be more sensitive to changes early in the disease. Of the few studies that have examined motor unit discharge in PD, the majority were conducted in the first dorsal interosseous, and no studies have measured motor units from extensor and …

Stable Readout Of Observed Actions From Format-Dependent Activity Of Monkey’S Anterior Intraparietal Neurons, Marco Lanzilotto, Monica Maranesi, Alessandro Livi, Carolina Giulia Ferroni, Guy A. Orban, Luca Bonini

Open Access Publications

No abstract provided.