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A Role For Malignant Brain Tumor Domain-Containing Protein 1 In Human Endometrial Stromal Cell Decidualization, Sangappa B Chadchan, Vineet K Maurya, Gwendalyn L Krekeler, Emily S Jungheim, Ramakrishna Kommagani

Open Access Publications

Up to 30% of women experience early miscarriage due to impaired decidualization. For implantation to occur, the uterine endometrial stromal fibroblast-like cells must differentiate into decidual cells, but the genes required for decidualization have not been fully defined. Here, we show that Malignant Brain Tumor Domain-containing Protein 1 (MBTD1), a member of the polycomb group protein family, is critical for human endometrial stromal cell (HESC) decidualization. MBTD1 predominantly localized to HESCs during the secretory phase and the levels were significantly elevated during

Therapies For Tuberculosis And Aids: Myeloid-Derived Suppressor Cells In Focus, Anca Dorhoi, Shabaana A Khader, Et Al

Open Access Publications

The critical role of suppressive myeloid cells in immune regulation has come to the forefront in cancer research, with myeloid-derived suppressor cells (MDSCs) as a main oncology immunotherapeutic target. Recent improvement and standardization of criteria classifying tumor-induced MDSCs have led to unified descriptions and also promoted MDSC research in tuberculosis (TB) and AIDS. Despite convincing evidence on the induction of MDSCs by pathogen-derived molecules and inflammatory mediators in TB and AIDS, very little attention has been given to their therapeutic modulation or roles in vaccination in these diseases. Clinical manifestations in TB are consequences of complex host-pathogen interactions and are …

The Tethering Function Of Mitofusin2 Controls Osteoclast Differentiation By Modulating The Ca2+–Nfatc1 Axis, Anna Ballard, Rong Zeng, Allahdad Zarei, Christine Shao, Linda Cox, Hui Yan, Antonietta Franco, Gerald W. Dorn Ii, Roberta Faccio, Deborah J. Veis

Open Access Publications

No abstract provided.

A Prospective Study Of Weight Gain In Women Diagnosed With Early-Stage Invasive Breast Cancer, Ductal Carcinoma In Situ, And Women Without Breast Cancer, Christine C. Ekenga, Xiaoyan Wang, Maria Pérez, Mario Schootman, Donna B. Jeffe

Open Access Publications

No abstract provided.

Impact Of Gender And Caregiving Responsibilities On Academic Success In Hematology, Allison A. King, Sara K. Vesely, Emily Vettese, Sadie Cook, Adam Cuker, Wendy Stock, Morgan Homer, Josel Fritz, Lilian Sung

Open Access Publications

No abstract provided.

Uncovering Tumour Heterogeneity Through Pkr And Nc886 Analysis In Metastatic Colon Cancer Patients Treated With 5-Fu-Based Chemotherapy, María Belén Ortega-García, Igor Zwir, Et Al

Open Access Publications

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by …

Photoreceptor Responses To Light In The Pathogenesis Of Diabetic Retinopathy, Shahriyar P Majidi, Rithwick Rajagopal

Open Access Publications

Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of …

Bet Bromodomain Inhibition Attenuates Cardiac Phenotype In Myocyte-Specific Lamin A/C-Deficient Mice, Gaelle Auguste, Leila Rouhi, Scot J Matkovich, Cristian Coarfa, Matthew J Robertson, Grazyna Czernuszewicz, Priyatansh Gurha, Ali J Marian

Open Access Publications

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. …

Deficiency Of Peroxiredoxin 2 Exacerbates Angiotensin Ii-Induced Abdominal Aortic Aneurysm, Se-Jin Jeong, Min Ji Cho, Na Young Ko, Sinai Kim, In-Hyuk Jung, Jeong-Ki Min, Sang Hak Lee, Jong-Gil Park, Goo Taeg Oh

Open Access Publications

No abstract provided.

Single Cell Transcriptomics Reveals Opioid Usage Evokes Widespread Suppression Of Antiviral Gene Program, Tanya T. Karagiannis, John P. Cleary Jr., Busra Gok, Andrew J. Henderson, Nicholas G. Martin, Masanao Yajima, Elliot C. Nelson, Christine S. Cheng

Open Access Publications

No abstract provided.

Peptidoglycan Editing Provides Immunity To Acinetobacter Baumannii During Bacterial Warfare, Nguyen-Hung Le, Gisela Di Venanzio, Juvenal Lopez, Seth W Hennon, Mario F Feldman, Et Al

Open Access Publications

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium

Early Diagnosis And Intervention In Cystic Fibrosis: Imagining The Unimaginable, Andrea M Coverstone, Thomas W Ferkol

Open Access Publications

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of …

Direct Neuronal Reprogramming Of Common Marmoset Fibroblasts By Ascl1, Microrna-9/9*, And Microrna-124 Overexpression, Akisa Nemoto, Reona Kobayashi, Sho Yoshimatsu, Yuta Sato, Takahiro Kondo, Andrew S Yoo, Seiji Shiozawa, Hideyuki Okano

Open Access Publications

The common marmoset (

Characterization Of Missense Mutations In The Signal Peptide And Propeptide Of Fix In Hemophilia B By A Cell-Based Assay, Wenwen Gao, Yaqi Xu, Hongli Liu, Meng Gao, Qing Cao, Yiyi Wang, Longteng Cui, Rong Huang, Yan Shen, Sanqiang Li, Haiping Yang, Yixiang Chen, Chaokun Li, Haichuan Yu, Weikai Li, Guomin Shen

Open Access Publications

No abstract provided.

Relationships Between Big-Five Personality Factors And Alzheimer's Disease Pathology In Autosomal Dominant Alzheimer's Disease, Andrew J Aschenbrenner, Jennifer Petros, Eric Mcdade, Guoqiao Wang, David A Balota, Tammie Ls Benzinger, Carlos Cruchaga, Chengjie Xiong, Richard Perrin, Anne M Fagan, John C Morris, Randall Bateman, Jason Hassenstab, Et Al

Open Access Publications

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD.

Methods: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to …

Therapeutic Enhancement Of Blood-Brain And Blood-Tumor Barriers Permeability By Laser Interstitial Thermal Therapy, Afshin Salehi, Mounica R Paturu, Bhuvic Patel, Matthew D Cain, Tatenda Mahlokozera, Alicia B Yang, Tsen-Hsuan Lin, Eric C Leuthardt, Hiroko Yano, Sheng-Kwei Song, Robyn S Klein, Robert Schmidt, Albert H Kim

Open Access Publications

BACKGROUND: The blood-brain and blood-tumor barriers (BBB and BTB), which restrict the entry of most drugs into the brain and tumor, respectively, are a significant challenge in the treatment of glioblastoma. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique increasingly used clinically for tumor cell ablation. Recent evidence suggests that LITT might locally disrupt BBB integrity, creating a potential therapeutic window of opportunity to deliver otherwise brain-impermeant agents.

METHODS: We established a LITT mouse model to test if laser therapy can increase BBB/BTB permeability in vivo. Mice underwent orthotopic glioblastoma tumor implantation followed by LITT in combination …

Macrophage Lc3-Associated Phagocytosis Is An Immune Defense Against Streptococcus Pneumoniae That Diminishes With Host Aging, Megumi Inomata, Shuying Xu, Pallavi Chandra, Simin N. Meydani, Genzou Takemura, Jennifer A. Philips, John M. Leong

Open Access Publications

No abstract provided.

Defining And Conceptualizing Outcomes For De-Implementation: Key Distinctions From Implementation Outcomes, Beth Prusaczyk, Taren Swindle, Geoffrey Curran

Open Access Publications

BACKGROUND: Increasingly, scholars argue that de-implementation is a distinct concept from implementation; factors contributing to stopping a current practice might be distinct from those that encourage adoption of a new one. One such distinction is related to de-implementation

CONCEPTUALIZATION OF OUTCOMES: We conceptualize each of the outcomes from Proctor and colleagues' taxonomy of implementation outcomes for de-implementation research. First, we suggest key considerations for researchers assessing de-implementation outcomes, such as considering how the cultural or historical significance to the practice may impact de-implementation success and, as others have stated, the importance of the patient in driving healthcare overuse. Second, we …

Induction Of Wnt16 Via Peptide-Mrna Nanoparticle-Based Delivery Maintains Cartilage Homeostasis, Huimin Yan, Ying Hu, Antonina Akk, Muhammad Farooq Rai, Hua Pan, Samuel A Wickline, Christine T N Pham

Open Access Publications

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants …

Ascot Identifies Key Regulators Of Neuronal Subtype-Specific Splicing, Jonathan P. Ling, Christopher Wilks, Rone Charles, Patrick J. Leavey, Devlina Ghosh, Lizhi Jiang, Clayton P. Santiago, Bo Pang, Anand Venkataraman, Brian S. Clark, Abhinav Nellore, Ben Langmead, Seth Blackshaw

Open Access Publications

No abstract provided.

5-Fluorocytosine Resistance Is Associated With Hypermutation And Alterations In Capsule Biosynthesis In Cryptococcus, R. Blake Billmyre, Shelly Applen Clancey, Lucy X. Li, Tamara L. Doering, Joseph Heitman

Open Access Publications

No abstract provided.

Structural Basis For Adhesion G Protein-Coupled Receptor Gpr126 Function, Katherine Leon, Rebecca L. Cunningham, Joshua A. Riback, Ezra Feldman, Jingxian Li, Tobin R. Sosnick, Minglei Zhao, Kelly R. Monk, Demet Araç

Open Access Publications

No abstract provided.

Structure Of A Rabies Virus Polymerase Complex From Electron Cryo-Microscopy, Joshua A. Horwitz, Simon Jenni, Stephen C. Harrison, Sean P. J. Whelan

Open Access Publications

No abstract provided.

Dill Extract Induces Elastic Fiber Neosynthesis And Functional Improvement In The Ascending Aorta Of Aged Mice With Reversal Of Age-Dependent Cardiac Hypertrophy And Involvement Of Lysyl Oxidase-Like-1, Wassim Fhayli, Quentin Boëté, Nadjib Kihal, Valérie Cenizo, Pascal Sommer, Walter A Boyle, Marie-Paule Jacob, Gilles Faury

Open Access Publications

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin …

Innate Immune Receptor Nod2 Mediates Lgr5+ Intestinal Stem Cell Protection Against Ros Cytotoxicity Via Mitophagy Stimulation, Antonin Levy, Aline Stedman, Eric Deutsch, Françoise Donnadieu, Herbert W. Virgin, Philippe J. Sansonetti, Giulia Nigro

Open Access Publications

No abstract provided.

Tumor Infiltrating Neutrophils Are Enriched In Basal-Type Urothelial Bladder Cancer, Giulio Eugenio Mandelli, Francesco Missale, Debora Bresciani, Luisa Benerini Gatta, Patrizia Scapini, Elena Caveggion, Elisa Roca, Mattia Bugatti, Matilde Monti, Luca Cristinelli, Sandra Belotti, Claudio Simeone, Stefano Calza, Laura Melocchi, William Vermi

Open Access Publications

BACKGROUND: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.

METHODS: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b

RESULTS: Basal type BC contained a significantly higher density of CD66b

CONCLUSIONS: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.

Loss-Of-Function Mutations In Udp-Glucose 6-Dehydrogenase Cause Recessive Developmental Epileptic Encephalopathy, Holger Hengel, Marisa V. Andrews, Marcia C. Willing, Et Al.

Open Access Publications

No abstract provided.

L-Plastin Deficiency Produces Increased Trabecular Bone Due To Attenuation Of Sealing Ring Formation And Osteoclast Dysfunction, Meenakshi A. Chellaiah, Megan C. Moorer, Sunipa Majumdar, Hanan Aljohani, Sharon C. Morley, Vanessa Yingling, Joseph P. Stains

Open Access Publications

No abstract provided.

Polycystin 2 Is Increased In Disease To Protect Against Stress-Induced Cell Death, Allison L. Brill, Tom T. Fischer, Jennifer M. Walters, Arnaud Marlier, Lorenzo R. Sewanan, Parker C. Wilson, Eric K. Johnson, Gilbert Moeckel, Lloyd G. Cantley, Stuart G. Campbell, Jeanne M. Nerbonne, Hee Jung Chung, Marie E. Robert, Barbara E. Ehrlich

Open Access Publications

No abstract provided.

A Wnt-Mediated Transformation Of The Bone Marrow Stromal Cell Identity Orchestrates Skeletal Regeneration, Yuki Matsushita, Mizuki Nagata, Kenneth M. Kozloff, Joshua D. Welch, Koji Mizuhashi, Nicha Tokavanich, Shawn A. Hallett, Daniel C. Link, Takashi Nagasawa, Wanida Ono, Noriaki Ono

Open Access Publications

No abstract provided.