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Archive for the ‘Innovations in Neurophysiology & Neuropsychology’ Category


Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders at https://www.amazon.com/dp/B078313281 – electronic Table of Contents 

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

Available on Kindle Store @ Amazon.com since 12/9/2017

List of Contributors & Contributors’ Biographies

Volume Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Preface, all Introductions, all Summaries and Epilogue

Part One:

1.4, 1.5, 1.6, 2.1.1, 2.1.2, 2.1.3, 2.1.4, 2.2.1, 2.2.2, 2.2.3, 2.3, 2.4, 2.4.1, 2.4.2, 2.5, 2.6.1, 2.6.2, 2.6.3, 2.6.4, 2.7, 2.8, 2.9, 2.10, 3.1, 3.2, 3.3, 3.4, 4.1, 4.2, 4.3

Part Two:

5.2, 5.3, 5.6, 6.1.2, 6.1.4, 6.2.1, 6.2.2, 6.3.2, 6.3.4, 6.3.5, 6.3.6, 6.3.8, 6.3.10, 6.4.1, 6.4.2, 6.5.1.2, 6.5.1.3, 6.5.2.2, 7.1, 7.2, 7.3, 7.4, 7.5, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 8.9.1, 8.9.3, 8.9.4, 8.9.5, 8.9.6, 8.10.1, 8.10.2, 8.10.3, 8.10.4, 9.2, 9.3, 9.5, 9.6, 9.7, 9.8, 9.9, 9.10, 9.11, 9.12, 9.13, 9.14, 9.15, 9.16, 10.2, 10.5, 10.6, 10.7, 10.8, 10.10, 10.11, 11.1, 11.2, 11.3, 11.5, 11.6, 11.7, 12.1, 12.2, 12.3, 12.4, 12.5, 12.7, 12.8, 12.9, 12.10, 12.11, 12.12, 13.1, 13.2, 13.3, 13.6, 13.12, 13.13, 14.1, 14.2

Guest Authors:

Pnina Abir-Am, PhD Part Two: 6.1.1

Stephen J Williams, PhDPart Two: 6.2.6, 6.5.2.2, 10.4, 10.9, 13.4

Aviva Lev-Ari, PhD, RN:

Part One:

1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 2.2.1, 2.3

Part Two:

5.1, 5.4, 5.5, 5.7, 5.8, 5.9, 5.10, 5.11, 6.1.3, 6.2.3, 6.2.4, 6.2.5, 6.3.1, 6.3.3, 6.3.7, 6.3.9, 6.4.3, 6.5.1.1, 6.5.2.1, 6.5.2.2, 6.5.3.1, 6.5.4, 6.5.5, 6,5,6, 8.9.2, 8.10.2, 9.1, 9.4, 10.1, 10.3, 11.4, 12.6, 13.5, 13.7, 13.8, 13.9, 13.10, 13.11

Adam Sonnenberg, BSC, MSc(c)Part Two: 13.9

 

electronic Table of Contents

PART ONE:

Physician as Authors, Writers in Medicine and Educator in Public Health

 

Chapter 1: Physicians as Authors

Introduction

1.1  The Young Surgeon and The Retired Pathologist: On Science, Medicine and HealthCare Policy – Best writers Among the WRITERS

1.2 Atul Gawande: Physician and Writer

1.3 Editorial & Publication of Articles in e-Books by  Leaders in Pharmaceutical Business Intelligence:  Contributions of Larry H Bernstein, MD, FCAP

1.4 Abraham Verghese, MD, Physician and Notable Author

1.5 Eric Topol, M.D.

1.6 Gregory House, MD

1.7 Peter Mueller, MD  Professor of Radiology @MGH & HMS – 2015 Synergy’s Honorary Award Recipient

Summary

Chapter 2: Professional Recognition

Introduction

2.1 Proceedings

2.1.1 Research Presentations

2.1.2 Proceedings of the NYAS

2.1.3 Cold Spring Harbor Conference Meetings

2.1.4 Young Scientist Seminars

2.2 Meet Great Minds

2.2.1 Meet the Laureates

2.2.2 Richard Feynman, Genius and Laureate

2.2.3 Fractals and Heat Energy

2.3 MacArthur Foundation Awards

2.4 Women’s Contributions went beyond Rosie the Riveter

2.4.1 Secret Maoist Chinese Operation Conquered Malaria

2.4.2 Antiparasite Drug Developers Win Nobel

2.5 Impact Factors and Achievement

2.6   RAPsodisiac Medicine

2.6.1 Outstanding-achievements-in-radiology-or-radiotherapy

2.6.2 Outstanding-achievement-in-anesthesiology

2.6.3 Outstanding-achievement-in-pathology

2.6.4 Topics in Pathology – Special Issues from Medscape Pathology

2.7 How to win the Nobel Prize

2.8 Conversations about Medicine

2.9 Current Advances in Medical Technology

2.10 Atul Butte, MD, PhD

Summary

Chapter 3:  Medical and Allied Health Sciences Education

Introduction

3.1 National Outstanding Medical Student Award Winners

3.2 Outstanding Awards in Medical Education

3.3 Promoting Excellence in Physicians and Nurses

3.4 Excellence in mentoring

Summary

Chapter 4: Science Teaching in Math and Technology (STEM)

Introduction

4.1 Science Teaching in Math and Technology

4.2 Television as a Medium for Science Education

4.2.1 Science Discovery TV

4.3 From Turing to Watson

Summary

PART TWO:

Medical Scientific Discoveries Interviews with Scientific Leaders

Chapter 5: Cardiovascular System

Introduction

5.1 Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem

5.2 Mitochondrial Dysfunction and Cardiac Disorders

5.3 Notable Contributions to Regenerative Cardiology

5.4 For Accomplishments in Cardiology and Cardiovascular Diseases: The Arrigo Recordati International Prize for Scientific Research

5.5 Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

5.6 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

5.7 CVD Prevention and Evaluation of Cardiovascular Imaging Modalities: Coronary Calcium Score by CT Scan Screening to justify or not the Use of Statin

5.8 2013 as A Year of Revolutionizing Medicine and Top 11 Cardiology Stories

5.9 Bridging the Gap in Medical Innovations – Elazer Edelman @ TEDMED 2013

5.10 Development of a Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinoma PIs: Jeffrey Clark (MGH), Robert Langer (Koch), Elazer Edelman (Harvard:MIT HST Program)

5.11 Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

Summary

Chapter 6: Genomics

Introduction
6.1 Genetics before the Human Genome Project

6.1.1 Why did Pauling Lose the “Race” to James Watson and Francis Crick? How Crick Describes his Discovery in a Letter to his Son

6.1.2 John Randall’s MRC Research Unit and Rosalind Franklin’s role at Kings College

6.1.3 Interview with the co-discoverer of the structure of DNA: Watson on The Double Helix and his changing view of Rosalind Franklin

6.1.4 The Initiation and Growth of Molecular Biology and Genomics, Part I

6.2 The Human Genome Project: Articles of Note  @ pharmaceuticalintelligence.com by multiple authors

6.2.1 CRACKING THE CODE OF HUMAN LIFE: The Birth of BioInformatics & Computational Genomics

6.2.2 What comes after finishing the Euchromatic Sequence of the Human Genome?

6.2.3 Human Genome Project – 10th Anniversary: Interview with Kevin Davies, PhD – The $1000 Genome

6.2.4 University of California Santa Cruz’s Genomics Institute will create a Map of Human Genetic Variations

6.2.5 Exceptional Genomes: The Process to find them

6.2.6 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

6.3 The Impact of Genome Sequencing on Biology and Medicine

6.3.1 Genomics in Medicine – Establishing a Patient-Centric View of Genomic Data

6.3.2 Modification of genes by homologous recombination – Mario Capecchi, Martin Evans, Oliver Smithies

6.3.3 AAAS February 14-18, 2013, Boston: Symposia – The Science of Uncertainty in Genomic Medicine

6.3.4 The Metabolic View of Epigenetic Expression

6.3.5  Pharmacogenomics

6.3.6 Neonatal Pathophysiology

6.3.7 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

6.3.8 3D mapping of genome in combine FISH and RNAi

6.3.9 Human Variome Project: encyclopedic catalog of sequence variants indexed to the human genome sequence

6.3.10 DNA mutagenesis and DNA repair

6.4 Scientific Leadership Recognition for Contributions to Genomics

6.4.1 Interview with Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak (44 minutes)

6.4.2 DNA Repair Pioneers Win Nobel – Tomas Lindahl, Paul Modrich, and Aziz Sancar 2015 Nobel Prize in Chemistry for the mechanisms of DNA repair

6.4.3  Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

6.5 Contemporary Field Leaders in Genomics

6.5.1 ROBERT LANGER

6.5.1.1 2014 Breakthrough Prizes Awarded in Fundamental Physics and Life Sciences for a Total of $21 Million – MIT’s Robert Langer gets $3 Million

6.5.1.2 National Medal of Science – 2006 Robert S. Langer

6.5.1.3  Confluence of Chemistry, Physics, and Biology

6.5.2 JENNIFER DOUDNA

6.5.2.1 Jennifer Doudna, cosmology teams named 2015 Breakthrough Prize winners

6.5.2.2 UPDATED – Medical Interpretation of the Genomics Frontier – CRISPR – Cas9: Gene Editing Technology for New Therapeutics

6.5.3 ERIC LANDER

6.5.3.1  2012 Harvey Prize in April 30: at the Technion-Israel Institute of Technology to Eric S. Lander @MIT & Eli Yablonovitch @UC, Berkeley

6.5.4 2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

6.5.5 Recognitions for Contributions in Genomics by Dan David Prize Awards

6.5.6   65 Nobel Laureates meet 650 young scientists covering the fields of physiology and medicine, physics, and chemistry, 28 June – 3 July, 2015, Lindau & Mainau Island, Germany

Summary

Chapter 7: The RNAs

Introduction

7.1 RNA polymerase – molecular basis for DNA transcription – Roger Kornberg, MD

7.2  One gene, one protein – Charles Yanofsky

7.3 Turning genetic information into working proteins – James E. Darnell Jr.

7.4 Small but mighty RNAs – Victor Ambros, David Baulcombe, and Gary Ruvkun, Phillip A. Sharp

7.5 Stress-response gene networks – Nina V. Fedoroff

Summary

Chapter 8: Proteomics, Protein-folding, and Cell Regulation
Introduction.

8.1 The Life and Work of Allan Wilson

8.2 Proteomics

8.3 More Complexity in Protein Evolution

8.4 Proteins: An evolutionary record of diversity and adaptation

8.5 Heroes in Basic Medical Research – Leroy Hood

8.6 Ubiquitin researchers win Nobel – Ciechanover, Hershko, and Rose awarded for discovery of ubiquitin-mediated proteolysis

8.7 Buffering of genetic modules involved in tricarboxylic acid cycle metabolism provides homeostatic regulation

8.8 Dynamic Protein Profiling

8.9 Protein folding

8.9.1 Protein misfolding and prions – Susan L. Lindquist, Stanley B. Prusiner

8.9.2 A Curated Census of Autophagy-Modulating Proteins and Small Molecules Candidate Targets for Cancer Therapy

8.9.3 Voluntary and Involuntary S-Insufficiency

8.9.4 Transthyretin and Lean Body Mass in Stable and Stressed State

8.9.5 The matter of stunting in the Ganges Plains

8.9.6 Proteins, Imaging and Therapeutics

8.10 Protein Folding and Vesicle Cargo

8.10.1 Heat Shock Proteins (HSP) and Molecular Chaperones

8.10.2 Collagen-binding Molecular Chaperone HSP47: Role in Intestinal Fibrosis – colonic epithelial cells and sub epithelial myofibroblasts

8.10.3 Biology, Physiology and Pathophysiology of Heat Shock Proteins

8.10.4 The Role of Exosomes in Metabolic Regulation 


Summary

Chapter 9:  Neuroscience

Introduction

9.1 Nobel Prize in Physiology or Medicine 2013 for Cell Transport: James E. Rothman of Yale University; Randy W. Schekman of the University of California, Berkeley; and Dr. Thomas C. Südhof of Stanford University

9.2 Proteins that control neurotransmitter release – Richard H. Scheller

9.3 Heroes in Basic Medical Research – Robert J. Lefkowitz

9.4 MIND AND MEMORY: BIOLOGICAL AND DIGITAL – 2014 Dan David Prize Symposium

9.5 A new way of moving – Michael Sheetz, James Spudich, Ronald Vale

9.6 Role the basal ganglia

9.7 The Neurogenetics of Language – Patricia Kuhl – 2015 George A. Miller Award

9.8 The structure of our visual system

9.9 Outstanding Achievement in Schizophrenia Research

9.10 George A. Miller, a Pioneer in Cognitive Psychology, Is Dead at 92

9.11 – To understand what happens in the brain to cause mental illness

9.12 Brain and Cognition

9.13 – To reduce symptoms of mental illness and retrain the brain

9.14 Behavior

9.15 Notable Papers in Neurosciences

9.16 Pyrroloquinoline quinone (PQQ) – an unproved supplement

Summary

Chapter 10: Microbiology & Immunology

Introduction

10.1 Reference Genes in the Human Gut Microbiome: The BGI Catalogue

10.2 Malnutrition in India, high newborn death rate and stunting of children age under five years

10.3 In His Own Words: Leonard Herzenberg, The Immunologist Who Revolutionized Research, Dies at 81

10.4 Heroes in Medical Research: Dr. Robert Ting, Ph.D. and Retrovirus in AIDS and Cancer

10.5 Tang Prize for 2014: Immunity and Cancer

10.6 Halstedian model of cancer progression

10.7 The History of Hematology and Related Sciences

10.8 Pathology Emergence in the 21st Century

10.9 Heroes in Medical Research: Barnett Rosenberg and the Discovery of Cisplatin

10.10  T cell-mediated immune responses & signaling pathways activated by TLRs – Bruce A. Beutler, Jules A. Hoffmann, Ralph M. Steinman

10.11 Roeder – the coactivator OCA-B, the first cell-specific coactivator, discovered by Roeder in 1992, is unique to immune system B cells

Summary

Chapter 11: Endocrine Hormones

Introduction

11.1 Obesity – 2010 Douglas L. ColemanJeffrey M. Friedman

11.2 Lonely Receptors: RXR – Jensen, Chambon, and Evans – Nuclear receptors provoke RNA production in response to steroid hormones

11.3 The Fred Conrad Koch Lifetime Achievement Award—the Society’s highest honor—recognizes the lifetime achievements and exceptional contributions of an individual to the field of endocrinology

11.4 Gerald D Aurbach Award for Outstanding Translational Research

11.5 Roy O. Greep Award for Outstanding Research in Endocrinology – Martin M. Matzuk

11.6 American Physiology Society Awards

11.7 Solomon Berson and Rosalyn Yalow

Summary

Chapter 12. Stem Cells

Introduction

12.1 Mature cells can be reprogrammed to become pluripotent – John Gurdon and Shinya Yamanaka

12.2 Observing the spleen colonies in mice and proving the existence of stem cells – Till and McCulloch

12.3 McEwen Award for Innovation: Irving Weissman, M.D., Stanford School of Medicine, and Hans Clevers, M.D., Ph.D., Hubrecht Institute

12.4 Developmental biology

12.5  CRISPR/Cas-mediated genome engineering – Rudolf Jaenisch

12.6 Ribozymes and RNA Machines –  Work of Jennifer A. Doudna

12.7 Ralph Brinster, ‘Father of Transgenesis’

12.8 Targeted gene modification

12.9 Stem Cells and Cancer

12.10 ALPSP Awards

12.11 Eppendorf Award for Young European Investigators

12.12 Breaking news about genomic engineering, T2DM and cancer treatments

Summary
Chapter 13: 3D Printing and Medical Application

Introduction

13.1 3D Printing

13.2 What is 3D printing?

13.3 The Scientist Who Is Making 3D Printing More Human

13.4 Join These Medical 3D Printing Groups on Twitter and LinkedIn for great up to date news

13.5 Neri Oxman and her Mediated Matter group @MIT Media Lab have developed a technique for 3D-printing Molten Glass

13.6 The ‘chemputer’ that could print out any drug

13.7 3-D-Bioprinting in use to Create Cardiac Living Tissue: Print your Heart out

13.8 LPBI’s Perspective on Medical and Life Sciences Applications – 3D Printing: BioInks, BioMaterials-BioPolymer

13.9 Medical MEMS, Sensors and 3D Printing: Frontier in Process Control of BioMaterials

13.10 NIH and FDA on 3D Printing in Medical Applications: Views for On-demand Drug Printing, in-Situ direct Tissue Repair and Printed Organs for Live Implants

13.11 ‘Pop-up’ fabrication technique trumps 3D printing

13.12 Augmentation of the ONTOLOGY of the 3D Printing Research

13.13 Superresolution Microscopy

Summary

Chapter 14: Synthetic Medicinal Chemistry

Introduction

14.1 Insights in Biological and Synthetic Medicinal Chemistry

14.2 Breakthrough work in cancer

Summary to Part Two

Volume Summary and Conclusions

EPILOGUE

 

 

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Diagnostic and Prognostic value of structural MRI: preliminary evidence of common and specific gray matter changes in Depression and Anxiety patients

Reporter: Aviva Lev-Ari, PhD, RN

 

Cortical thickening in the insular cortex, a brain region vital to perception and self-awareness in Patients with

  • Social anxiety disorder (SAD)
  • Major depressive disorder (MDD)

greater cortical thickness may reflect a

  • compensatory mechanism that is related to inflammation or other aspects of the pathophysiology,” she said.
  • greater anterior cingulate cortical thickness could be the result of both the continuous coping efforts and emotion regulation attempts of MDD and SAD patients.”

Image Source: There are significant cortical thickness differences among the three groups. All regions survived clusterwise-correction (p<0.001).(Credit: Radiological Society of North America)

SOURCE

MRI Uncovers Brain Abnormalities in People with Depression and Anxiety

https://www.mdtmag.com/news/2017/11/mri-uncovers-brain-abnormalities-people-depression-and-anxiety?et_cid=6181014&et_rid=461755519&location=top&et_cid=6181014&et_rid=461755519&linkid=https%3a%2f%2fwww.mdtmag.com%2fnews%2f2017%2f11%2fmri-uncovers-brain-abnormalities-people-depression-and-anxiety%3fet_cid%3d6181014%26et_rid%3d%%subscriberid%%%26location%3dtop

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2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall (ex-Brandeis, University of Maine), Michael Rosbash (Brandeis University) and Michael W. Young (Rockefeller University in New York) for their discoveries of molecular mechanisms controlling the circadian rhythm

 

Curator: Aviva Lev-Ari, PhD, RN

 

Press Release

2017-10-02

The Nobel Assembly at Karolinska Institutet has today decided to award

the 2017 Nobel Prize in Physiology or Medicine

jointly to

Jeffrey C. Hall, Michael Rosbash and Michael W. Young

for their discoveries of molecular mechanisms controlling the circadian rhythm

READ the Summary

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html

 

Jeffrey C. Hall was born 1945 in New York, USA. He received his doctoral degree in 1971 at the University of Washington in Seattle and was a postdoctoral fellow at the California Institute of Technology in Pasadena from 1971 to 1973. He joined the faculty at Brandeis University in Waltham in 1974. In 2002, he became associated with University of Maine.

Michael Rosbash was born in 1944 in Kansas City, USA. He received his doctoral degree in 1970 at the Massachusetts Institute of Technology in Cambridge. During the following three years, he was a postdoctoral fellow at the University of Edinburgh in Scotland. Since 1974, he has been on faculty at Brandeis University in Waltham, USA.

Michael W. Young was born in 1949 in Miami, USA. He received his doctoral degree at the University of Texas in Austin in 1975. Between 1975 and 1977, he was a postdoctoral fellow at Stanford University in Palo Alto. From 1978, he has been on faculty at the Rockefeller University in New York.

 

Key publications

Zehring, W.A., Wheeler, D.A., Reddy, P., Konopka, R.J., Kyriacou, C.P., Rosbash, M., and Hall, J.C. (1984). P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster. Cell 39, 369–376.

Bargiello, T.A., Jackson, F.R., and Young, M.W. (1984). Restoration of circadian behavioural rhythms by gene transfer in Drosophila. Nature 312, 752–754.

Siwicki, K.K., Eastman, C., Petersen, G., Rosbash, M., and Hall, J.C. (1988). Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system. Neuron 1, 141–150.

Hardin, P.E., Hall, J.C., and Rosbash, M. (1990). Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536–540.

Liu, X., Zwiebel, L.J., Hinton, D., Benzer, S., Hall, J.C., and Rosbash, M. (1992). The period gene encodes a predominantly nuclear protein in adult Drosophila. J Neurosci 12, 2735–2744.

Vosshall, L.B., Price, J.L., Sehgal, A., Saez, L., and Young, M.W. (1994). Block in nuclear localization of period protein by a second clock mutation, timeless. Science 263, 1606–1609.

Price, J.L., Blau, J., Rothenfluh, A., Abodeely, M., Kloss, B., and Young, M.W. (1998). double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94, 83–95.

Keeping time on our human physiology

The biological clock is involved in many aspects of our complex physiology. We now know that all multicellular organisms, including humans, utilize a similar mechanism to control circadian rhythms. A large proportion of our genes are regulated by the biological clock and, consequently, a carefully calibrated circadian rhythm adapts our physiology to the different phases of the day (Figure 3). Since the seminal discoveries by the three laureates, circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing.

The circadian clock

Figure 3. The circadian clock anticipates and adapts our physiology to the different phases of the day. Our biological clock helps to regulate sleep patterns, feeding behavior, hormone release, blood pressure, and body temperature.

SOURCE

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html

 

Medicine Nobel awarded for work on circadian clocks, Jeffrey Hall, Michael Rosbash and Michael Young unpicked molecular workings of cells’ daily rhythms.

Ewen CallawayHeidi Ledford

02 October 2017

https://www.nature.com/news/medicine-nobel-awarded-for-work-on-circadian-clocks-1.22736?WT.ec_id=NEWSDAILY-20171002

Other Related Research 

Charles Weitz, Ph.D., M.D.
Robert Henry Pfeiffer Professor of Neurobiology

Mammalian Circadian Clocks

Circadian clocks are molecular oscillators with ~24-hour periods that drive daily biological rhythms.  Such clocks are found in all of the major branches of life, and they likely represent ancient timekeeping systems important for predicting daily environmental cycles on our rotating planet.  In mammals, circadian clocks are present in most if not all cells. These distributed clocks control a myriad of processes, in aggregate creating coherent 24-hour programs of physiology and behavior.

A picture of how circadian clocks are built has emerged in the last two decades.  The core mechanism is a transcriptional feedback loop, wherein the protein products of several clock genes build the molecular machinery to inhibit the transcription factor responsible for their own production.  The molecular components of circadian clocks are conserved from insects to humans.

The Weitz lab uses molecular biology, biochemistry, genetics, and structural biology to investigate the mammalian circadian clock.  The focus of our efforts at present is to understand the circadian clock in terms of the integrated functions of its several multi-protein machines.  This effort is principally based on the purification of endogenous circadian clock protein complexes from mouse tissues and their biochemical analysis and structural study by cryo-electron microscopy.

Fig. 1.  Class-average electron microscopy images of the mouse nuclear PER complex, a core circadian clock machine.  It is a 1.9-MDa assembly of about thirty proteins that appears as a quasi-spherical, beaded particle of 40-nm diameter. Our current work provides an initial low-resolution view of the structural organization of endogenous clock machinery from a eukaryote.  We aim to obtain high-resolution structures.

Selected papers:

Duong HA, Robles MS, Knutti K, Weitz CJ.  A molecular mechanism for circadian clock negative feedback. Science  332, 1436-1439 (2011).

Padmanabhan K, Robles MS, Westerling T, Weitz CJ.  Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science  337, 599-602 (2012).

Kim JY, Kwak PB, Weitz CJ. Specificity in circadian clock feedback from targeted reconstitution of the NuRD co-repressor.  Mol. Cell  56, 738-748 (2014).

Aryal RA, Kwak PB, Tamayo AG, Chiu PL, Walz T, Weitz CJ.  Macromolecular assemblies of the mammalian circadian clock.  Mol. Cell  (2017, in press).

SOURCE

http://neuro.hms.harvard.edu/people/faculty/charles-weitz

Circadian Clock’s Inner Gears

https://hms.harvard.edu/news/circadian-clock%E2%80%99s-inner-gears?utm_source=linkedin&utm_medium=social&utm_campaign=hms-linkedin-general

Other related articles Published in this Open Access Online Scientific Journal included the following: 

Search Keyword “Sleep” – 161 Scientific Articles

https://pharmaceuticalintelligence.com/?s=Sleep

Search Keyword “Circadian” Rhythm

Ultra-Pure Melatonin Product Helps Maintain Sleep for Up to 7 Hours

Curator: Gail S. Thornton, M.A.

https://pharmaceuticalintelligence.com/2017/06/11/ultra-pure-melatonin-product-helps-maintain-sleep-for-up-to-7-hours/

 

Alteration in Reduced Glutathione level in Red Blood Cells: Role of Melatonin

Author: Shilpa Chakrabarti, PhD

https://pharmaceuticalintelligence.com/2013/06/11/alteration-in-reduced-glutathione-level-in-red-blood-cells-role-of-melatonin/

 

Melatonin and its effect on acetylcholinesterase activity in erythrocytes

Author: S. Chakravarty, PhD

https://pharmaceuticalintelligence.com/2013/03/09/melatonin-and-its-effect-on-acetylcholinesterase-activity-in-erythrocytes/

 

Day and Night Variation in Melatonin Level affects Plasma Membrane Redox System in Red Blood Cells

Author: Shilpa Chakravarty, PhD

https://pharmaceuticalintelligence.com/2013/02/23/httpwww-ncbi-nlm-nih-govpubmed22561555/

 

Prolonged Wakefulness: Lack of Sufficient Duration of Sleep as a Risk Factor for Cardiovascular Diseases – – Indications for Cardiovascular Chrono-therapeutics

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/02/prolonged-wakefulness-lack-of-sufficient-duration-of-sleep-as-a-risk-factor-for-cardiovascular-diseases-indications-for-cardiovascular-chrono-therapeutics/

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Post-zygotic Mutations, spontaneously arising in an embryonic cell after sperm meets egg, are important players in Autism Spectrum Disorder, a HMS & BCH large study suggests

Reporter: Aviva Lev-Ari, PhD, RN

 

Based on their findings, they classified 7.5 percent of ASD subjects’ de novo mutations as PZMs. Of these, 83 percent had not been picked up in the original analysis of their genome sequence.

Some PZMs affected genes already known to be linked to autism or other neurodevelopmental disorders (such as SCN2AHNRNPU and SMARCA4), but sometimes affected these genes in different ways. Many other PZMs were in genes known to be active in brain development (such as KLF16 and MSANTD2) but not previously associated with ASD.

Comparing these with the genomic sequencing data (based mostly on blood DNA samples) allowed the researchers estimate the timing of the PZMs and the brain regions they affected. In the image at right, representing the prenatal brain, the region with the most “hits” was the amygdala (AMY, in red), with minor hits in the striatum (STR) and cerebellar cortex (CBC) that did not reach statistical significance.

Image Credit: Mohammed Uddin

 

SOURCES

Late-breaking mutations may play an important role in autism

https://vector.childrenshospital.org/2017/07/post-zygotic-somatic-mutations-autism/

Late in the Game, Post-conception mutations may play an important role in autism

https://hms.harvard.edu/news/late-game?utm_source=Silverpop&utm_medium=email&utm_term=s3&utm_content=8.7.17.HMS

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Nature Neuroscience (2017) doi:10.1038/nn.4598
Published online: 17 July 2017

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Cause of Alzheimer’s Discovered: protein SIRT6 role in DNA repair process – low levels enable DNA damage accumulation

Reporter: Aviva Lev-Ari, PhD, RN

 

According to lead author Dr. Deborah Toiber of the BGU Department of Life Sciences, “If a decrease in SIRT6 and lack of DNA repair is the beginning of the chain that ends in neurodegenerative diseases in seniors, then we should be focusing our research on how to maintain production of SIRT6 and avoid the DNA damage that leads to these diseases.”

Publications

Neuroprotective functions for the histone deacetylase SIRT6

Shai Kaluski Miguel Portillo, Antoine Besnard, Daniel Stein, Monica Einav, Lei Zhong, Uwe Ueberham, Thomas Arendt, Raul Mostoslavsky, Amar Sahay, Debra Toiber

Cell Reports 2017 Mar 28;18(13):3052-3062

Long noncoding RNA: noncoding and not coded.

Toiber D, Leprivier G, Rotblat B.

Cell Death Discov. 2017 Jan 9;3:16104. doi: 10.1038/cddiscovery.2016.104.

SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.

Toiber D, Erdel F, Bouazoune K, Silberman DM, Zhong L, Mulligan P, Sebastian C, Cosentino C, Martinez-Pastor B, Giacosa S, D’Urso A, Näär AM, Kingston R, Rippe K, Mostoslavsky R.

Mol Cell. 2013 Aug 22;51(4):454-68. doi: 10.1016/j.molcel.2013.06.018.

The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism.

Sebastián C, Zwaans BM, Silberman DM, Gymrek M, Goren A, Zhong L, Ram O, Truelove J, Guimaraes AR, Toiber D, Cosentino C, Greenson JK, MacDonald AI, McGlynn L, Maxwell F, Edwards J, Giacosa S, Guccione E, Weissleder R, Bernstein BE, Regev A, Shiels PG, Lombard DB, Mostoslavsky R.

Cell. 2012 Dec 7;151(6):1185-99. doi: 10.1016/j.cell.2012.10.047.

Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor.

Cohen-Kfir E, Artsi H, Levin A, Abramowitz E, Bajayo A, Gurt I, Zhong L, D’Urso A, Toiber D, Mostoslavsky R, Dresner-Pollak R.

Endocrinology. 2011 Dec;152(12):4514-24. doi: 10.1210/en.2011-1128.

Characterization of nuclear sirtuins: molecular mechanisms and physiological relevance.

Toiber D, Sebastian C, Mostoslavsky R.

Handb Exp Pharmacol. 2011; 206:189-224. doi: 10.1007/978-3-642-21631-2_9.

A SIRT1-LSD1 corepressor complex regulates Notch target gene expression and development.

Mulligan P, Yang F, Di Stefano L, Ji JY, Ouyang J, Nishikawa JL, Toiber D, Kulkarni M, Wang Q, Najafi-Shoushtari SH, Mostoslavsky R, Gygi SP, Gill G, Dyson NJ, Näär AM.

Mol Cell. 2011 Jun 10;42(5):689-99. doi: 10.1016/j.molcel.2011.04.020.

Engineering DYRK1A overdosage yields Down syndrome-characteristic cortical splicing aberrations.

Toiber D, Azkona G, Ben-Ari S, Torán N, Soreq H, Dierssen M.

Neurobiol Dis. 2010 Oct;40(1):348-59. doi: 10.1016/j.nbd.2010.06.011.

Acetylcholinesterase variants in Alzheimer’s disease: from neuroprotection to programmed cell death.

Greenberg DS, Toiber D, Berson A, Soreq H.

Neurodegener Dis. 2010;7(1-3):60-3. doi: 10.1159/000285507.

The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha.

Zhong L, D’Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R.

Cell. 2010 Jan 22;140(2):280-93. doi: 10.1016/j.cell.2009.12.041.

Pro-apoptotic protein-protein interactions of the extended N-AChE terminus.

Toiber D, Greenberg DS, Soreq H.

J Neural Transm 2009 Nov;116(11):1435-42. doi: 10.1007/s00702-009-0249-2.

N-acetylcholinesterase-induced apoptosis in Alzheimer’s disease.

Toiber D, Berson A, Greenberg D, Melamed-Book N, Diamant S, Soreq H.

PLoS One. 2008 Sep 1;3(9):e3108. doi: 10.1371/journal.pone.0003108.

A novel isoform of acetylcholinesterase exacerbates photoreceptors death after photic stress.

Kehat R, Zemel E, Cuenca N, Evron T, Toiber D, Loewenstein A, Soreq H, Perlman I.

Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1290-7.

Modulated splicing-associated gene expression in P19 cells expressing distinct acetylcholinesterase splice variants.

Ben-Ari S*, Toiber D*, Sas AS, Soreq H, Ben-Shaul Y.

J Neurochem. 2006 Apr;97 Suppl 1:24-34.

  • ​*Equal contribution

Cellular stress reactions as putative cholinergic links in Alzheimer’s disease.

Toiber D, Soreq H.

Neurochem Res. 2005 Jun-Jul;30(6-7):909-19.

Function of alternative splicing.

Stamm S, Ben-Ari S, Rafalska I, Tang Y, Zhang Z, Toiber D, Thanaraj TA, Soreq H.

Gene. 2005 Jan 3;344:1-20.

Combinatorial complexity of 5′ alternative acetylcholinesterase transcripts and protein products.

Meshorer E, Toiber D, Zurel D, Sahly I, Dori A, Cagnano E, Schreiber L, Grisaru D, Tronche F, Soreq H.

J Biol Chem. 2004 Jul 9;279(28):29740-51.

SOURCE

https://toiber.wixsite.com/toiber-lab/publications

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2017 award recipients including Thomas S. Kilduff, PhD, Director, Center for Neuroscience at SRI International in Menlo Park, California

 

Reporter: Aviva Lev-Ari, PhD, RN

I was Director of the Business and Economic Statistics Program at SRI International in Menlo Park, California, 1985-1988.

Sleep Research Society announces 2017 award recipients

Sleep Research Society
Friday, April 28, 2017

DARIEN, IL – Several of the world’s leading sleep and circadian scientists were selected as recipients of the 2017 Sleep Research Society awards, which will be presented Monday, June 5, during the plenary session of SLEEP 2017, the 31st annual meeting of the Associated Professional Sleep Societies LLC (APSS) in Boston.

“The Sleep Research Society awards recognize individuals who have made significant and lasting contributions to sleep and circadian science,” said SRS President Sean P.A. Drummond, PhD. “I congratulate each of the recipients of the 2017 awards and appreciate all that they have done to help the SRS achieve its mission to advance sleep and circadian science.”

The 2017 SRS award recipients, who were selected by the SRS board of directors, are:

Thomas S. Kilduff, PhD
Distinguished Scientist Award for significant, original and sustained scientific contributions of a basic, clinical or theoretical nature to the sleep and circadian research field, made over an entire career
Dr. Kilduff directs the Center for Neuroscience at SRI International in Menlo Park, California. He is co-discoverer of the neuropeptide hypocretin (orexin), a key neurotransmitter in the maintenance of wakefulness. His group at SRI has identified a cortical interneuron population that is activated during sleep in proportion to homeostatic sleep drive, and their work also focuses on therapeutic development for insomnia and narcolepsy.

As the SRS Distinguished Scientist Award recipient, Dr. Kilduff also receives the honor of presenting an invited lecture at the SLEEP 2017 annual meeting. He will present the lecture, “Identifying Novel Sleep/Wake Targets: Hypocretin/Orexin, Cortical nNOS Neurons, and TAAR1,” on Tuesday, June 6, at the Hynes Convention Center in Boston.

Niels C. Rattenborg, PhD
Outstanding Scientific Achievement Award for novel and seminal discoveries of a basic, clinical or theoretical nature that have made a significant impact on the sleep field
Dr. Rattenborg is the leader of the Avian Sleep Group at the Max Planck Institute for Ornithology (MPIO) in Seewiesen, Germany. His research, published in August 2016 in the journal Nature Communications, was the first to demonstrate sleep in flying birds. Using electroencephalogram recordings of great frigatebirds flying over the ocean for up to 10 days, his team found that the birds can sleep with either one hemisphere at a time or both hemispheres simultaneously. However, while in flight they sleep for a much smaller percentage of time than they do while on land, which challenges the dominant view that large daily amounts of sleep are required to maintain adaptive performance.

Colin A. Espie, PhD, DSc
Mary A. Carskadon Outstanding Educator Award for excellence in the field of education related to sleep medicine and sleep research
Dr. Espie is professor of sleep medicine in the Nuffield Department of Clinical Neuroscience and a Fellow of Somerville College at the University of Oxford in England. He is research director of the Experimental and Clinical Sleep Medicine program within the Sleep & Circadian Neuroscience Institute and clinical director of the Oxford Online Program in Sleep Medicine.

Photos are available upon request. For more information, please contact Specialty Society Coordinator Barbara Hoeft at 630-737-9700, ext. 9321, or bhoeft@srsnet.org.

About the Sleep Research Society
The Sleep Research Society (SRS) is a professional membership society that advances sleep and circadian science. The SRS provides forums for the exchange of information, establishes and maintains standards of reporting and classifies data in the field of sleep research, and collaborates with other organizations to foster scientific investigation on sleep and its disorders. The SRS also publishes the peer-reviewed, scientific journal SLEEP.

SOURCE

http://www.sleepresearchsociety.org/articles.aspx?id=6867

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Drugs that activate this novel stress response pathway, which they call the mitochondrial-to-cytosolic stress response, protected both nematodes and cultured human cells with Huntington´s disease from protein-folding damage.

Reporter: Aviva Lev-Ari, PhD, RN

 

“Maybe there is a way to use one drug to alter the mitochondrial signal and another drug to alter the communciation signal from the brain,” he said. “You would never see these two effects if you were studying protein folding in a tissue culture dish, because you don’t have the whole organism, C. elegans, in which you can look at the signals being communicated.”

Co-authors of the fat study include Hyun-Eui Kim, Ana Rodrigues Grant, Milos Simic, Rebecca Kohnz, Daniel Nomura, Jenni Durieux, Celine Riera, Melissa Sanchez, Erik Kapernick and Suzanne Wolff at UC Berkeley. The second study was co-authored by Kristen Berendzen, Jenni Durieux, Ye Tian, Hyun-eui Kim and Suzanne Wolff of UC Berkeley, in collaboration with Li-Wa Shao and Ying Liu of Peking University in Beijing.

The studies are supported by the Howard Hughes Medical Institute, National Institutes of Health, Glenn Foundation for Medical Research, and Jane Coffin Childs Memorial Fund for Medical Research.

RELATED INFORMATION

SOURCE

Can some types of fat protect us from brain disease?

 

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