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Palladin Is A Neuron-Specific Translational Target Of Mtor Signaling That Regulates Axon Morphogenesis, Yusuke Umegaki, Antonio Martínez Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi

Open Access Publications

The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates …

Decreasing Recurrent Bowel Obstructions, Improving Quality Of Life With Physiotherapy: Controlled Study, Amanda D Rice, Kimberley Patterson, Evette D Reed, Belinda F Wurn, Kristen Robles, Bernhard Klingenberg, Leonard B Weinstock, Janey S. A. Pratt, C. Richard King Iii, Lawrence J Wurn

Open Access Publications

AIM: To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy

METHODS: One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, …

Parabiosis And Single-Cell Rna Sequencing Reveal A Limited Contribution Of Monocytes To Myofibroblasts In Kidney Fibrosis, Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys

Open Access Publications

Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney …

Myeloid Conditioning With C-Kit-Targeted Car-T Cells Enables Donor Stem Cell Engraftment, Yasuyuki Arai, Uimook Choi, Cristina I Corsino, Sherry M Koontz, Masaki Tajima, Colin L Sweeney, Mary A Black, Steven A Feldman, Mary C Dinauer, Harry L Malech

Open Access Publications

We report a novel approach to bone marrow (BM) conditioning using c-kit-targeted chimeric antigen receptor T (c-kit CAR-T) cells in mice. Previous reports using anti-c-kit or anti-CD45 antibody linked to a toxin such as saporin have been promising. We developed a distinctly different approach using c-kit CAR-T cells. Initial studies demonstrated in vitro killing of hematopoietic stem cells by c-kit CAR-T cells but poor expansion in vivo and poor migration of CAR-T cells into BM. Pre-treatment of recipient mice with low-dose cyclophosphamide (125 mg/kg) together with CXCR4 transduction in the CAR-T cells enhanced trafficking to and expansion in BM (<1%-13.1%). This resulted in significant depletion of the BM c-kit

Sall1 Functions As A Tumor Suppressor In Breast Cancer By Regulating Cancer Cell Senescence And Metastasis Through The Nurd Complex, Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng

Open Access Publications

BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.

METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor …

Interleukin-7 Restores Lymphocytes In Septic Shock: The Iris-7 Randomized Clinical Trial, Bruno Francois, Andrew H Walton, Jacqueline Unsinger, Teresa Blood, Jane Blood, Richard S Hotchkiss, Et Al

Open Access Publications

BACKGROUND: A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity.

METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 …

Physiological Mechanisms Of Sustained Fumagillin-Induced Weight Loss, Jie An, Michael L Patnode, Vanessa K Ridaura, Jeffrey I Gordon, Et Al

Open Access Publications

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by …

Tnf Receptor-Activated Factor 2 Mediates Cardiac Protection Through Noncanonical Nf-Κb Signaling, Sarah Evans, Huei-Ping Tzeng, Deborah J Veis, Scot Matkovich, Carla Weinheimer, Attila Kovacs, Philip M Barger, Douglas L Mann

Open Access Publications

To elucidate the mechanisms responsible for cytoprotective effects of TNF receptor-activated factor 2 (TRAF2) in the heart, we employed genetic gain- and loss-of-function studies ex vivo and in vivo in mice with cardiac-restricted overexpression of TRAF2 (Myh6-TRAF2LC). Crossing Myh6-TRAF2LC mice with mice lacking canonical signaling (Myh6-TRAF2LC/Myh6-IκBαΔN) abrogated the cytoprotective effects of TRAF2 ex vivo. In contrast, inhibiting the JAK/STAT pathway did not abrogate the cytoprotective effects of TRAF2. Transcriptional profiling of WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IκBαΔN mouse hearts suggested that the noncanonical NF-κB signaling pathway was upregulated in the Myh6-TRAF2LC mouse hearts. Western blotting and ELISA for the NF-κB family proteins …

Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu

Open Access Publications

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 …

Incorporating Reflection Boundary Conditions In The Neumann Series Radiative Transport Equation: Application To Photon Propagation And Reconstruction In Diffuse Optical Imaging, Abhinav K. Jha, Yansong Zhu, Simon Arridge, Dean F. Wong, Arman Rahmim

Open Access Publications

No abstract provided.

Deletion Of Tsc2 In Nociceptors Reduces Target Innervation, Ion Channel Expression, And Sensitivity To Heat, Dan Carlin, Judith P. Golden, Amit Mogha, Vijay K. Samineni, Kelly R. Monk, Robert W. Gereau, Valeria Cavalli

Open Access Publications

No abstract provided.

Trpv1 Agonist, Capsaicin, Induces Axon Outgrowth After Injury Via Ca2+/Pka Signaling, Erin Frey, Scott Karney-Grobe, Trevor Krolak, Jeff Milbrandt, Aaron Diantonio

Open Access Publications

No abstract provided.

Feasibility Of Co-Registered Ultrasound And Acoustic-Resolution Photoacoustic Imaging Of Human Colorectal Cancer, Xiandong Leng, William Chapman, Bin Rao, Sreyankar Nandy, Ruimin Chen, Rehan Rais, Ivan Gonzalez, Qifa Zhou, Deyali Chatterjee, Matthew Mutch, Quing Zhu

Open Access Publications

No abstract provided.

Fat Composition In Infant Formula Contributes To The Severity Of Necrotising Enterocolitis, Chhinder P. Sodhi, William B. Fulton, Misty Good, Mustafa Vurma, Tapas Das, Chron-Si Lai, Hongpeng Jia, Yukihiro Yamaguchi, Peng Lu, Thomas Prindle Jr, John A. Ozolek, David J. Hackam

Open Access Publications

No abstract provided.

Reprogramming Glioblastoma Multiforme Cells Into Neurons By Protein Kinase Inhibitors, Jie Yuan, Fan Zhang, Dennis Hallahan, Zhen Zhang, Liming He, Ling-Gang Wu, Meng You, Qin Yang

Open Access Publications

No abstract provided.

Gpr56/Adgrg1 Regulates Development And Maintenance Of Peripheral Myelin, Sarah D. Ackerman, Amit Mogha, Breanne L. Harty, Mitchell D'Rozario, Nicholas E. Sanchez, Paul Gamble, Matthew R. Macewan, Wilson Zachary Ray, Kelly R. Monk, Et Al

Open Access Publications

No abstract provided.

Hile Regulates Hild By Blocking Dna Binding In Salmonella Enterica Serovar Typhimurium, Jesse R. Grenz, Jessica E. Cott Chubiz, Pariyaman Thaprawat, James M. Slauch

Open Access Publications

No abstract provided.

Multilevel Correlates Of Household Anthropometric Typologies In Colombian Mothers And Their Infants, D. C. Parra, L. F. Gomez, L. Iannotti, D. Haire-Joshu, A. K. Sebert Kuhlmann, R. C. Brownson

Open Access Publications

No abstract provided.

Construction, Expression, And Characterization Of Rsea-Egf And In Vitro Evaluation Of Its Antitumor Activity Against Nasopharyngeal Cancer, Xueting Liu, Liping Zeng, Zhongqiu Zhou, Yang Xie, Shan Wang, Junyan Zhang, Ying He, Zehong Zou, Jianguo Zhang, Ailin Tao

Open Access Publications

No abstract provided.

The Toxoplasma Gondii Active Serine Hydrolase 4 Regulates Parasite Division And Intravacuolar Parasite Architecture, Ian T. Foe, Ouma Onguka, Katherine Amberg-Johnson, Rikki M. Garner, Neri Amara, Wandy Beatty, Ellen Yeh, Matthew Bogyo

Open Access Publications

No abstract provided.

The Immediate Early Gene Egr3 Is Required For Hippocampal Induction Of Bdnf By Electroconvulsive Stimulation, Kimberly T. Meyers, Ketan K. Marballi, Samuel J. Brunwasser, Briana Renda, Milad Charbel, Diano F. Marrone, Amelia L. Gallitano

Open Access Publications

No abstract provided.

Burosumab Therapy In Children With X-Linked Hypophosphatemia, Thomas O. Carpenter, Michael P. Whyte, Erik A. Imel, Annemieke M. Boot, Wolfgang Hogler, Agnes Linglart, Raja Padidela, William Van't Hoff, Meng Mao, Chao-Yin Chen, Alison Skrinar, Emil Kakkis, Javier San Martin, Anthony A. Portale

Open Access Publications

No abstract provided.

Diltiazem Improves Contractile Properties Of Skeletal Muscle In Dysferlin‐Deficient Blaj Mice, But Does Not Reduce Contraction‐Induced Muscle Damage, Morium Begam, Alyssa F. Collier, Amber L. Mueller, Renuka Roche, Sujay S. Galen, Joseph A. Roche

Open Access Publications

No abstract provided.

Characterization Of Small Molecules Inhibiting The Pro-Angiogenic Activity Of The Zinc Finger Transcription Factor Vezf1, Ming He, Qianyi Yang, Allison B. Norvil, David Sherris, Humaira Gowher

Open Access Publications

No abstract provided.

Geogenomic Segregation And Temporal Trends Of Human Pathogenic Escherichia Coli O157:H7, Washington, Usa, 2005-2014, Gillian A. M. Tarr, Smriti Shringi, Amanda I. Phipps, Thomas E. Besser, Jonathan Mayer, Hanna N. Oltean, Jon Wakefield, Phillip I. Tarr, Peter Rabinowitz

Open Access Publications

No abstract provided.

Valuation Of Knowledge And Ignorance In Mesolimbic Reward Circuitry, Caroline J. Charpentier, Ethan S. Bromberg-Martin, Tali Sharot

Open Access Publications

No abstract provided.

New Insights Into The Role Of Trem2 In Alzheimer’S Disease, Maud Gratuze, Cheryl E.G. Leyns, David M. Holtzman

Open Access Publications

No abstract provided.

Scn Vip Neurons Are Essential For Normal Light-Mediated Resetting Of The Circadian System, Jeff R. Jones, Tatiana Simon, Lorenzo Lones, Erik D. Herzog

Open Access Publications

No abstract provided.

Genetically Enhancing The Expression Of Chemokine Domain Of Cx3cl1 Fails To Prevent Tau Pathology In Mouse Models Of Tauopathy, Shane M. Bemiller, Nicole M. Maphis, Shane V. Formica, Gina N. Wilson, Crystal M. Miller, Guixiang Xu, Olga N. Kokiko-Cochran, Ki-Wook Kim, Steffen Jung, Judy L. Cannon, Samuel D. Crish, Astrid E. Cardona, Bruce T. Lamb, Kiran Bhaskar

Open Access Publications

No abstract provided.

Age-Specific Global Epidemiology Of Hydrocephalus: Systematic Review, Metanalysis And Global Birth Surveillance, Albert M. Isaacs, Jay Riva-Cambrin, Daniel Yavin, Aaron Hockley, Tamara M. Pringsheim, Nathalie Jette, Brendan Cord Lethebe, Mark Lowerison, Jarred Dronyk, Mark G. Hamilton

Open Access Publications

No abstract provided.