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Mitochondrial Fusion Supports Increased Oxidative Phosphorylation During Cell Proliferation, Cong-Hui Yao, Rencheng Wang, Yahui Wang, Che-Pei Kung, Jason D. Weber, Gary J. Patti

Open Access Publications

Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion. Impairing mitochondrial fusion by knocking down mitofusion-2 (Mfn2) was sufficient to attenuate proliferation, while overexpressing Mfn2 increased proliferation. Interestingly, impairing mitochondrial fusion decreased OXPHOS but did not deplete ATP levels. Instead, inhibition caused cells to transition from excreting …

Multiancestry Genome-Wide Association Study Of Lipid Levels Incorporating Gene-Alcohol Interactions, Paul S. De Vries, Yun J. Sung, Karen Schwander, Aldi T. Kraja, Mary F. Feitosa, Lisa De Las Fuentes, Renee De Mutsert, C Charles Gu, Yize Li, Treva K. Rice, Lihua Wang, Christine Williams, Mary K. Wojczynski, Michael A. Province, Dabeeru C. Rao, Et Al

Open Access Publications

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test …

Apo-Opsin Exists In Equilibrium Between A Predominant Inactive And A Rare Highly Active State, Shinya Sato, Beata Jastrzebska, Andreas Engel, Krzysztof Palczewski, Vladimir J. Kefalov

Open Access Publications

Bleaching adaptation in rod photoreceptors is mediated by apo-opsin, which activates phototransduction with effective activity 10

A Randomized, Placebo-Controlled Trial Of Fidaxomicin For Prophylaxis Of Clostridium Difficile-Associated Diarrhea In Adults Undergoing Hematopoietic Stem Cell Transplantation, Kathleen M. Mullane, Erik R. Dubberke, Et Al

Open Access Publications

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients.

Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. …

Meta-Analysis Of Up To 622,409 Individuals Identifies 40 Novel Smoking Behaviour Associated Genetic Loci, A Mesut Erzurumluoglu, Mengzhen Liu, Victoria E. Jackson, Arpana Agrawal, Laura Bierut, Yi-Ling Chou, Andrew Heath, Pamela A F Madden, John Rice, Et Al

Open Access Publications

No abstract provided.

Inducible Down-Regulation Of Mhc Class I Results In Natural Killer Cell Tolerance, Michael D. Bern, Bijal A. Parikh, Liping Yang, Diana L. Beckman, Jennifer Poursine-Laurent, Wayne M. Yokoyama

Open Access Publications

Natural killer (NK) cells are innate lymphocytes that are thought to kill cells that down-regulate MHC class I (MHC-I) through "missing-self" recognition. NK cells from

Association Between 5-Year Clinical Outcome In Patients With Nonmedically Evacuated Mild Blast Traumatic Brain Injury And Clinical Measures Collected Within 7 Days Postinjury In Combat, Christine L. Mac Donald, Jason Barber, Jana Patterson, Ann M. Johnson, Sureyya Dikmen, Jesse R. Fann, Nancy Temkin

Open Access Publications

Importance: Although previous work has examined clinical outcomes in combat-deployed veterans, questions remain regarding how symptoms evolve or resolve following mild blast traumatic brain injury (TBI) treated in theater and their association with long-term outcomes.

Objective: To characterize 5-year outcome in patients with nonmedically evacuated blast concussion compared with combat-deployed controls and understand what clinical measures collected acutely in theater are associated with 5-year outcome.

Design, Setting, and Participants: A prospective, longitudinal cohort study including 45 service members with mild blast TBI within 7 days of injury (mean 4 days) and 45 combat deployed nonconcussed controls was carried out. Enrollment …

The Transcriptional Regulator Snon Promotes The Proliferation Of Cerebellar Granule Neuron Precursors In The Postnatal Mouse Brain, Xiaoying Chen, Ayan Chanda, Yoshiho Ikeuchi, Xiaoqing Zhang, Jared V. Goodman, Naveen C. Reddy, Shahriyar P. Majidi, Dennis Y. Wu, Sarah E. Smith, Abigail Godec, Anna Oldenborg, Harrison W. Gabel, Guoyan Zhao, Shirin Bonni, Azad Bonni

Open Access Publications

Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional KO of the transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal male and female mouse brain. In laser capture microdissection …

Voltage-Independent Sk-Channel Dysfunction Causes Neuronal Hyperexcitability In The Hippocampus Of Fmr1 Knock-Out Mice, Pan-Yue Deng, Dan Carlin, Young Mi Oh, Leila K. Myrick, Stephen T. Warren, Valeria Cavalli, Vitaly A. Klyachko

Open Access Publications

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (K

Bronchial Thermoplasty: A Decade Of Experience: State Of The Art, Laren D Tan, Ken Y Yoneda, Samuel Louie, D Kyle Hogarth, Mario Castro

Open Access Publications

Bronchial thermoplasty (BT) delivers targeted radiofrequency energy to bronchial airway walls and results in the partial ablation of the airway smooth muscle that is responsible for bronchoconstriction. It is approved for the treatment of severe persistent asthma. Multiple, large clinical trials including a recent "real-world" study demonstrate significant improvements in asthma-related quality of life, reduction in asthma exacerbations, emergency department visits, and hospitalizations after BT that is sustained out to 5 years. In this article, we review the state of the art of BT treatment in severe persistent asthma and share a decade of BT research and clinical experience. We …

Phosphatidylcholine Synthesis Through Cholinephosphate Cytidylyltransferase Is Dispensable In Leishmania Major, Samrat Moitra, Mattie C. Pawlowic, Fong-Fu Hsu, Kai Zhang

Open Access Publications

No abstract provided.

Hospital Revisits Within 30 Days After Discharge For Medical Conditions Targeted By The Hospital Readmissions Reduction Program In The United States: National Retrospective Analysis, Rishi K. Wadhera, Karen E. Joynt Maddox, Dhruv S. Kazi, Changyu Shen, Robert W. Yeh

Open Access Publications

No abstract provided.

A Short Translational Ramp Determines The Efficiency Of Protein Synthesis, Manasvi Verma, Junhong Choi, Kyle A. Cottrell, Zeno Lavagnino, Erica N. Thomas, Slavica Pavlovic-Djuranovic, Pawel Szczesny, David W. Piston, Hani S. Zaher, Joseph D. Puglisi, Sergej Djuranovic

Open Access Publications

No abstract provided.

The Architecture Of Functional Lateralisation And Its Relationship To Callosal Connectivity In The Human Brain, Vyacheslav R. Karolis, Maurizio Corbetta, Michel Thiebaut De Schotten

Open Access Publications

No abstract provided.

Favorable Cardiovascular Health At Young And Middle Ages And Dementia In Older Age—The Cha Study, Thanh-Huyen T. Vu, Lihui Zhao, Lei Liu, Cuiping Schiman, Donald M. Lloyd-Jones, Martha L. Daviglus, Kiang Liu, Daniel B. Garside, Jeremiah Stamler, James F. Fries, Ya-Chen Tina Shih, Norrina B. Allen

Open Access Publications

No abstract provided.

Endothelial Glycocalyx: Role In Body Fluid Homeostasis And Fluid Management, Pankaj Kundra, Shreya Goswami

Open Access Publications

No abstract provided.

Independent Associations Of Tomm40 And Apoe Variants With Body Mass Index, Alexander M. Kulminski, Yury Loika, Irina Culminskaya, Jian Huang, Konstantin G. Arbeev, Olivia Bagley, Mary F. Feitosa, Joseph M. Zmuda, Kaare Christensen, Anatoliy I. Yashin, Long Life Family Study Research Group

Open Access Publications

No abstract provided.

An Analog Of Glibenclamide Selectively Enhances Autophagic Degradation Of Misfolded Α1-Antitrypsin Z, Yan Wang, Murat C. Cobanoglu, Tunda Hidvegi, Pamela Hale, Michael Ewing, Andrew S. Chu, Zhenwei Gong, Radhika Muzumdar, Stephen C. Pak, Gary A. Silverman, Ivet Bahar, David H. Perlmutter

Open Access Publications

No abstract provided.

Simulation-Based Remediation In Emergency Medicine Residency Training- A Consensus Study, Nur-Ain Nadir, Danielle Hart, Michael Cassara, Joan Noelker, Tiffany Moadel, Miriam Kulkarni, Christopher Sampson, Suzanne Bentley, Neel Naik, Jessica Hernandez, Sara Krzyzaniak, Steven Lai, Gregory Podolej, Christopher Strother

Open Access Publications

No abstract provided.

Persistent Metabolic Youth In The Aging Female Brain, Manu S. Goyal, Tyler M. Blazey, Yi Su, Lars E. Couture, Tony J. Durbin, Randall J. Bateman, Tammie L.-S. Benzinger, John C. Morris, Marcus E. Raichle, Andrei G. Vlassenko

Open Access Publications

No abstract provided.

Cells Exhibiting Strong P16ink4a Promoter Activation In Vivo Display Features Of Senescence, Jie-Yu Liu, George P. Souroullas, Brian O. Diekman, Janakiraman Krishnamurthy, Brandon M. Hall, Jessica A. Sorrentino, Joel S. Parker, Garrett A. Sessions, Andrei V. Gudkov, Norman E. Sharpless

Open Access Publications

No abstract provided.

Self-Transcendence In Mountaineering And Base Jumping, Erik Monasterio, C. Robert Cloninger

Open Access Publications

No abstract provided.

Chronic Pain And Chronic Opioid Use After Intensive Care Discharge – Is It Time To Change Practice?, Dusica M. Stemenkovic, Helen Laycock, Menelaos Karanikolas, Nebojsa Gojko Ladjevic, Vojislava Neskovic, Carsten Bantel

Open Access Publications

No abstract provided.

Nicotine Oxidation By Genetic Variants Of Cyp2b6 And In Human Brain Microsomes, Adam Joseph Bloom, Pan-Fen Wang, Evan D. Kharasch

Open Access Publications

No abstract provided.

Neuronal Evidence For Good-Based Economic Decisions Under Variable Action Costs, Xinying Cai, Camillo Padoa-Schioppa

Open Access Publications

No abstract provided.

Trans-Ethnic Kidney Function Association Study Reveals Putative Causal Genes And Effects On Kidney-Specific Disease Aetiologies, Haojia Wu, Benjamin D. Humphreys, Andrew C. Heath, Pamela A. F. Madden

Open Access Publications

No abstract provided.

Novel Chitohexaose Analog Protects Young And Aged Mice From Clp Induced Polymicrobial Sepsis, Pragnya Das, Santosh K. Panda, Beamon Agarwal, Sumita Behera, Syed M. Ali, Mark E. Pulse, Joseph S. Solomkin, Steven M. Opal, Vineet Bhandari, Suchismita Acharya

Open Access Publications

No abstract provided.

Role Of Arginase 2 In Systemic Metabolic Activity And Adipose Tissue Fatty Acid Metabolism In Diet-Induced Obese Mice, Reem T. Atawia, Haroldo A. Toque, Mohamed M. Meghil, Tyler W. Benson, Nicole K.H Yiew, Christopher W. Cutler, Neal L. Weintraub, Ruth B. Caldwell, Robert W. Caldwell

Open Access Publications

No abstract provided.

A Longitudinally Extensive Spinal Cord Lesion Restricted To Gray Matter In An Adolescent Male, Danielle Golub, Faith Williams, Taylor Wong, Nishanth Iyengar, Hannah Jolley, Sakinah Sabadiah, David Rhee, Gabrielle Gold-Von Simson

Open Access Publications

No abstract provided.

X-Ray Structures Of The High-Affinity Copper Transporter Ctr1, Feifei Ren, Brandon L. Logeman, Xiaohui Zhang, Yongjian Liu, Dennis J. Thiele, Peng Yuan

Open Access Publications

No abstract provided.