ALBERT

Description: 〈p〉While deregulation of mitochondrial metabolism and cytosolic glycolysis has been well recognized in tumor cells, the role of coordinated mitochondrial oxidation and cytosolic fermentation of pyruvate, a key metabolite derived from glucose, in physiological processes is not well understood. Here, we report that knockout of 〈i〉PTPMT1〈/i〉, a mitochondrial phosphoinositide phosphatase, completely blocked postnatal cerebellar development. Proliferation of granule cell progenitors, the most actively replicating cells in the developing cerebellum, was only moderately decreased, and proliferation of Purkinje cell progenitors did not seem to be affected in knockout mice. In contrast, generation of functional Bergmann glia from multipotent precursor cells (radial glia), which is essential for cerebellar corticogenesis, was totally disrupted. Moreover, despite a low turnover rate, neural stem cells were impaired in self-renewal in knockout mice. Mechanistically, loss of PTPMT1 decreased mitochondrial aerobic metabolism by limiting utilization of pyruvate, which resulted in bioenergetic stress in neural precursor/stem cells but not in progenitor or mature cells, leading to cell cycle arrest through activation of the AMPK-p19/p21 pathway. This study suggests that mitochondrial oxidation of the carbohydrate fuel is required for postnatal cerebellar development, and identifies a bioenergetic stress–induced cell cycle checkpoint in neural precursor/stem cells.〈/p〉

Description: While deregulation of mitochondrial metabolism and cytosolic glycolysis has been well recognized in tumor cells, the role of coordinated mitochondrial oxidation and cytosolic fermentation of pyruvate, a key metabolite derived from glucose, in physiological processes is not well understood. Here, we report that knockout of PTPMT1 , a mitochondrial phosphoinositide phosphatase, completely blocked postnatal cerebellar development. Proliferation of granule cell progenitors, the most actively replicating cells in the developing cerebellum, was only moderately decreased, and proliferation of Purkinje cell progenitors did not seem to be affected in knockout mice. In contrast, generation of functional Bergmann glia from multipotent precursor cells (radial glia), which is essential for cerebellar corticogenesis, was totally disrupted. Moreover, despite a low turnover rate, neural stem cells were impaired in self-renewal in knockout mice. Mechanistically, loss of PTPMT1 decreased mitochondrial aerobic metabolism by limiting utilization of pyruvate, which resulted in bioenergetic stress in neural precursor/stem cells but not in progenitor or mature cells, leading to cell cycle arrest through activation of the AMPK-p19/p21 pathway. This study suggests that mitochondrial oxidation of the carbohydrate fuel is required for postnatal cerebellar development, and identifies a bioenergetic stress–induced cell cycle checkpoint in neural precursor/stem cells.

Description: 〈p〉Focusing light deep by engineering wavefronts toward guide stars inside scattering media has potential biomedical applications in imaging, manipulation, stimulation, and therapy. However, the lack of endogenous guide stars in biological tissue hinders its translations to in vivo applications. Here, we use a reversibly switchable bacterial phytochrome protein as a genetically encoded photochromic guide star (GePGS) in living tissue to tag photons at targeted locations, achieving light focusing inside the tissue by wavefront shaping. As bacterial phytochrome-based GePGS absorbs light differently upon far-red and near-infrared illumination, a large dynamic absorption contrast can be created to tag photons inside tissue. By modulating the GePGS at a distinctive frequency, we suppressed the competition between GePGS and tissue motions and formed tight foci inside mouse tumors in vivo and acute mouse brain tissue, thus improving light delivery efficiency and specificity. Spectral multiplexing of GePGS proteins with different colors is an attractive possibility.〈/p〉

Description: 〈p〉By using click chemistry, a hexacationic cage was synthesized. The cage contains two triscationic -electron–deficient trispyridiniumtriazine (TPZ〈sup〉3+〈/sup〉) platforms that are bridged in a face-to-face manner by three ethylene-triazole-ethylene linkers. A diversity of -electron–rich guests can be recognized within the pocket of the cage, driven by host-guest - interactions. The cage cavity acts as a protecting group, preventing an anthracene guest from undergoing Diels-Alder reaction. Under ultraviolet (UV) light, the pyridinium CN bonds in TPZ〈sup〉3+〈/sup〉 platforms are polarized and weakened, resulting in the occurrence of cage decomposition via β-elimination. Guest recognition could help to prevent this UV-stimulated cage decomposition by suppressing the excitation of the TPZ〈sup〉3+〈/sup〉 units.〈/p〉

Description: Cytosolic RNA sensing is a prerequisite for initiation of innate immune response against RNA viral pathogens. Signaling through RIG-I (retinoic acid–inducible gene I)–like receptors (RLRs) to TBK1 (Tank-binding kinase 1)/IKK (IB kinase ) kinases is transduced by mitochondria-associated MAVS (mitochondrial antiviral signaling protein). However, the precise mechanism of how MAVS-mediated TBK1/IKK activation is strictly controlled still remains obscure. We reported that protein phosphatase magnesium-dependent 1A (PPM1A; also known as PP2Cα), depending on its catalytic ability, dampened the RLR-IRF3 (interferon regulatory factor 3) axis to silence cytosolic RNA sensing signaling. We demonstrated that PPM1A was an inherent partner of the TBK1/IKK complex, targeted both MAVS and TBK1/IKK for dephosphorylation, and thus disrupted MAVS-driven formation of signaling complex. Conversely, a high level of MAVS can dissociate the TBK1/PPM1A complex to override PPM1A-mediated inhibition. Loss of PPM1A through gene ablation in human embryonic kidney 293 cells and mouse primary macrophages enabled robustly enhanced antiviral responses. Consequently, Ppm1a –/– mice resisted to RNA virus attack, and transgenic zebrafish expressing PPM1A displayed profoundly increased RNA virus vulnerability. These findings identify PPM1A as the first known phosphatase of MAVS and elucidate the physiological function of PPM1A in antiviral immunity on whole animals.

Description: Plant immunity against foreign gene invasion takes advantage of posttranscriptional gene silencing (PTGS). How plants elaborately avert inappropriate PTGS of endogenous coding genes remains unclear. We demonstrate in Arabidopsis that both 5'-3' and 3'-5' cytoplasmic RNA decay pathways act as repressors of transgene and endogenous PTGS. Disruption of bidirectional cytoplasmic RNA decay leads to pleiotropic developmental defects and drastic transcriptomic alterations, which are substantially rescued by PTGS mutants. Upon dysfunction of bidirectional RNA decay, a large number of 21- to 22-nucleotide endogenous small interfering RNAs are produced from coding transcripts, including multiple microRNA targets, which could interfere with their cognate gene expression and functions. This study highlights the risk of unwanted PTGS and identifies cytoplasmic RNA decay pathways as safeguards of plant transcriptome and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Xinyan -- Zhu, Ying -- Liu, Xiaodan -- Hong, Xinyu -- Xu, Yang -- Zhu, Ping -- Shen, Yang -- Wu, Huihui -- Ji, Yusi -- Wen, Xing -- Zhang, Chen -- Zhao, Qiong -- Wang, Yichuan -- Lu, Jian -- Guo, Hongwei -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):120-3. doi: 10.1126/science.aaa2618.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China. ; Biodynamic Optical Imaging Center, School of Life Sciences, Peking University, Beijing 100871, China. ; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ; State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ; State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. hongweig@pku.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25838384" target="_blank"〉PubMed〈/a〉

Description: Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Homsy, Jason -- Zaidi, Samir -- Shen, Yufeng -- Ware, James S -- Samocha, Kaitlin E -- Karczewski, Konrad J -- DePalma, Steven R -- McKean, David -- Wakimoto, Hiroko -- Gorham, Josh -- Jin, Sheng Chih -- Deanfield, John -- Giardini, Alessandro -- Porter, George A Jr -- Kim, Richard -- Bilguvar, Kaya -- Lopez-Giraldez, Francesc -- Tikhonova, Irina -- Mane, Shrikant -- Romano-Adesman, Angela -- Qi, Hongjian -- Vardarajan, Badri -- Ma, Lijiang -- Daly, Mark -- Roberts, Amy E -- Russell, Mark W -- Mital, Seema -- Newburger, Jane W -- Gaynor, J William -- Breitbart, Roger E -- Iossifov, Ivan -- Ronemus, Michael -- Sanders, Stephan J -- Kaltman, Jonathan R -- Seidman, Jonathan G -- Brueckner, Martina -- Gelb, Bruce D -- Goldmuntz, Elizabeth -- Lifton, Richard P -- Seidman, Christine E -- Chung, Wendy K -- T32 HL007208/HL/NHLBI NIH HHS/ -- Arthritis Research UK/United Kingdom -- British Heart Foundation/United Kingdom -- Department of Health/United Kingdom -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1262-6. doi: 10.1126/science.aac9396.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA, USA. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. ; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. ; Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, USA. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation and Trust and Imperial College London, London, UK. National Heart & Lung Institute, Imperial College London, London, UK. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. Howard Hughes Medical Institute, Harvard University, Boston, MA, USA. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Department of Cardiology, University College London and Great Ormond Street Hospital, London, UK. ; Department of Pediatrics, University of Rochester Medical Center, The School of Medicine and Dentistry, Rochester, NY, USA. ; Section of Cardiothoracic Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. ; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. Yale Center for Genome Analysis, Yale University, New Haven, CT, USA. ; Yale Center for Genome Analysis, Yale University, New Haven, CT, USA. ; Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, NY, USA. ; Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, USA. Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY, USA. ; Department of Neurology, Columbia University Medical Center, New York, NY, USA. ; Department of Pediatrics, Columbia University Medical Center, New York, NY, USA. ; Department of Cardiology, Children's Hospital Boston, Boston, MA, USA. ; Division of Pediatric Cardiology, University of Michigan, Ann Arbor, MI, USA. ; Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. ; Department of Cardiology, Boston Children's Hospital, Boston, MA, USA. ; Department of Pediatric Cardiac Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. ; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. ; Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA. ; Heart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, MD, USA. ; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. bruce.gelb@mssm.edu goldmuntz@email.chop.edu martina.brueckner@yale.edu richard.lifton@yale.edu cseidman@genetics.med.harvard.edu wkc15@cumc.columbia.edu. ; Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bruce.gelb@mssm.edu goldmuntz@email.chop.edu martina.brueckner@yale.edu richard.lifton@yale.edu cseidman@genetics.med.harvard.edu wkc15@cumc.columbia.edu. ; Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. bruce.gelb@mssm.edu goldmuntz@email.chop.edu martina.brueckner@yale.edu richard.lifton@yale.edu cseidman@genetics.med.harvard.edu wkc15@cumc.columbia.edu. ; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. Howard Hughes Medical Institute, Yale University, New Haven, CT, USA. bruce.gelb@mssm.edu goldmuntz@email.chop.edu martina.brueckner@yale.edu richard.lifton@yale.edu cseidman@genetics.med.harvard.edu wkc15@cumc.columbia.edu. ; Department of Genetics, Harvard Medical School, Boston, MA, USA. Howard Hughes Medical Institute, Harvard University, Boston, MA, USA. Cardiovascular Division, Brigham & Women's Hospital, Harvard University, Boston, MA, USA. bruce.gelb@mssm.edu goldmuntz@email.chop.edu martina.brueckner@yale.edu richard.lifton@yale.edu cseidman@genetics.med.harvard.edu wkc15@cumc.columbia.edu. ; Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA. bruce.gelb@mssm.edu goldmuntz@email.chop.edu martina.brueckner@yale.edu richard.lifton@yale.edu cseidman@genetics.med.harvard.edu wkc15@cumc.columbia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785492" target="_blank"〉PubMed〈/a〉

Description: Liu et al (Research Article, 30 October 2015, p. 530) described a lithium-oxygen (Li-O2) battery based on lithium iodide (LiI)-assisted lithium hydroxide (LiOH) formation and decomposition. We argue that LiOH cannot be oxidized by triiodide (I3 (-)). The charge capacity is from the oxidation of I(-) instead of LiOH. The limited-capacity cycling test is misleading when the electrolyte contributes considerable parasitic reaction capacity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Yue -- Zhang, Wang -- Chou, Shu-Lei -- Dou, Shi-Xue -- New York, N.Y. -- Science. 2016 May 6;352(6286):667. doi: 10.1126/science.aaf1399.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Material Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China. shenyue1213@hust.edu.cn shulei@uow.edu.au. ; State Key Laboratory of Material Processing and Die and Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China. ; Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, Innovation Campus, Squires Way, North Wollongong NSW 2522, Australia. shenyue1213@hust.edu.cn shulei@uow.edu.au. ; Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, Innovation Campus, Squires Way, North Wollongong NSW 2522, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27151858" target="_blank"〉PubMed〈/a〉

Description: Outbreaks of Middle East respiratory syndrome (MERS) raise questions about the prevalence and evolution of the MERS coronavirus (CoV) in its animal reservoir. Our surveillance in Saudi Arabia in 2014 and 2015 showed that viruses of the MERS-CoV species and a human CoV 229E-related lineage co-circulated at high prevalence, with frequent co-infections in the upper respiratory tract of dromedary camels. viruses of the betacoronavirus 1 species, we found that dromedary camels share three CoV species with humans. Several MERS-CoV lineages were present in camels, including a recombinant lineage that has been dominant since December 2014 and that subsequently led to the human outbreaks in 2015. Camels therefore serve as an important reservoir for the maintenance and diversification of the MERS-CoVs and are the source of human infections with this virus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sabir, Jamal S M -- Lam, Tommy T-Y -- Ahmed, Mohamed M M -- Li, Lifeng -- Shen, Yongyi -- Abo-Aba, Salah E M -- Qureshi, Muhammd I -- Abu-Zeid, Mohamed -- Zhang, Yu -- Khiyami, Mohammad A -- Alharbi, Njud S -- Hajrah, Nahid H -- Sabir, Meshaal J -- Mutwakil, Mohammed H Z -- Kabli, Saleh A -- Alsulaimany, Faten A S -- Obaid, Abdullah Y -- Zhou, Boping -- Smith, David K -- Holmes, Edward C -- Zhu, Huachen -- Guan, Yi -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):81-4. doi: 10.1126/science.aac8608. Epub 2015 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. ; Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Department of Nucleic Acids Research, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, Borg El-Arab, Post Office Box 21934, Alexandria, Egypt. ; Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. ; Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Microbial Genetics Department, Genetic Engineering and Biotechnology Division, National Research Center, Dokki, Giza, Egypt. ; King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia. ; Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. ; Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. ; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia. ; State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. zhuhch@hku.hk yguan@hku.hk. ; Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. State Key Laboratory of Emerging Infectious Diseases (The University of Hong Kong-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen, China. Shantou University-The University of Hong Kong Joint Institute of Virology, Shantou University, Shantou, China. Centre of Influenza Research and State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. zhuhch@hku.hk yguan@hku.hk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26678874" target="_blank"〉PubMed〈/a〉

Description: Carbon’s unique ability to have both sp 2 and sp 3 bonding states gives rise to a range of physical attributes, including excellent mechanical and electrical properties. We show that a series of lightweight, ultrastrong, hard, elastic, and conductive carbons are recovered after compressing sp 2 -hybridized glassy carbon at various temperatures. Compression induces the local buckling of graphene sheets through sp 3 nodes to form interpenetrating graphene networks with long-range disorder and short-range order on the nanometer scale. The compressed glassy carbons have extraordinary specific compressive strengths—more than two times that of commonly used ceramics—and simultaneously exhibit robust elastic recovery in response to local deformations. This type of carbon is an optimal ultralight, ultrastrong material for a wide range of multifunctional applications, and the synthesis methodology demonstrates potential to access entirely new metastable materials with exceptional properties.