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Archive for the ‘Gene Regulation and Evolution’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Biologists may have been building a more nuanced view of sex, but society has yet to catch up. True, more than half a century of activism from members of the lesbian, gay, bisexual and transgender community has softened social attitudes to sexual orientation and gender. Many societies are now comfortable with men and women crossing conventional societal boundaries in their choice of appearance, career and sexual partner. But when it comes to sex, there is still intense social pressure to conform to the binary model.

 

This pressure has meant that people born with clear DSDs (difference/disorder of sex development) often undergo surgery to ‘normalize’ their genitals. Such surgery is controversial because it is usually performed on babies, who are too young to consent, and risks assigning a sex at odds with the child’s ultimate gender identity — their sense of their own gender. Intersex advocacy groups have therefore argued that doctors and parents should at least wait until a child is old enough to communicate their gender identity, which typically manifests around the age of three, or old enough to decide whether they want surgery at all.

 

As many as 1 person in 100 has some form of “DSD” with or without external manifestation. Diagnoses of DSDs previously relied on hormone tests, anatomical inspections and imaging, followed by painstaking tests of one gene at a time. Now, advances in genetic techniques mean that teams can analyze multiple genes at once, aiming straight for a genetic diagnosis and making the process less stressful for families. Children with DSDs are treated by multidisciplinary teams that aim to tailor management and support to each individual and their family, but this usually involves raising a child as male or female even if no surgery is done.

 

The simple scenario that all learn is that two X chromosomes make someone female, and an X and a Y chromosome make someone male. These are simplistic ways of thinking about what is scientifically very complex. Anatomy, hormones, cells, and chromosomes (and also personal identity convictions) are actually not usually aligned with this binary classification.

 

More than 25 genes that affect sex development have now been identified, and they have a wide range of variations that affect people in subtle ways. Many differences aren’t even noticed until incidental medical encounters, such as a forty-six-year-old woman pregnant with her third child, found after amniocentesis that half her cells carry male chromosomes. Or a seventy-year-old father of three who learns during a hernia repair that he has a uterus.

 

Furthermore, scientists now understood that everyone’s body is made up of a patchwork of genetically distinct cells, some of which may have a different sex than the rest. This “mosaicism” can have effects ranging from undetectable to extraordinary, such as “identical” twins of different sexes. An extremely common instance of mosaicism comes from cells passing over the placental barrier during pregnancy. Men often carry female cells from their mothers, and women carry male cells from their sons. Research has shown that these cells remain present for decades, but what effects they have on disease and behavior is an essentially unstudied question.

 

References:

 

https://www.theguardian.com/science/2017/mar/02/cambridge-scientists-create-first-self-developing-embryo-from-stem-cells

 

https://www.ncbi.nlm.nih.gov/pubmed/25693544

 

http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.34123/abstract;jsessionid=A330AD995EE25C7A0AD5EA478694ADD8.f04t01

 

https://www.ncbi.nlm.nih.gov/pubmed/25091731

 

https://www.ncbi.nlm.nih.gov/pubmed/1695712

 

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Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing

Curator: Aviva Lev-Ari, PhD, RN

 

This article presents Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single molecule DNA sequencing

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Ido Sagi – PhD Student @HUJI, 2017 Kaye Innovation Award winner for leading research that yielded the first successful isolation and maintenance of haploid embryonic stem cells in humans.

Reporter: Aviva Lev-Ari, PhD, RN

 

Ido Sagi – PhD Student, Silberman Institute of Life Sciences, HUJI, Israel

  • Ido Sagi’s research focuses on studying genetic and epigenetic phenomena in human pluripotent stem cells, and his work has been published in leading scientific journals, including NatureNature Genetics and Cell Stem Cell.
  • Ido Sagi received BSc summa cum laude in Life Sciences from the Hebrew University, and currently pursues a PhD at the laboratory of Prof. Nissim Benvenisty at the university’s Department of Genetics in the Alexander Silberman Institute of Life Sciences.

The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society.

Publications – Ido Sagi

Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors.
Cell Stem Cell 2014 Nov 6;15(5):634-42. Epub 2014 Nov 6.
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA; Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address:

November 2014

 



Stem cells: Aspiring to naivety.
Nature 2016 12 30;540(7632):211-212. Epub 2016 Nov 30.
The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
November 2016

Download Full Paper

SOURCE

Other related articles on Genetic and Epigenetic phenomena in human pluripotent stem cells published by LPBI Group can be found in the following e-Books on Amazon.com

e-Books in Medicine

https://www.amazon.com/s/ref=dp_byline_sr_ebooks_9?ie=UTF8&text=Aviva+Lev-Ari&search-alias=digital-text&field-author=Aviva+Lev-Ari&sort=relevancerank

9 results for Kindle Store : “Aviva Lev-Ari”

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    Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics

    Nov 28, 2015 | Kindle eBook

    by Justin D. Pearlman MD ME PhD MA FACC and Stephen J. Williams PhD
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    Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery (Series C Book 2)

    May 13, 2017 | Kindle eBook

    by Larry H. Bernstein and Demet Sag
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    Perspectives on Nitric Oxide in Disease Mechanisms (Biomed e-Books Book 1)

    Jun 20, 2013 | Kindle eBook

    by Margaret Baker PhD and Aviva Lev-Ari PhD RN
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    Cancer Biology and Genomics for Disease Diagnosis (Series C: e-Books on Cancer & Oncology Book 1)

    Aug 10, 2015 | Kindle eBook

    by Larry H Bernstein MD FCAP and Prabodh Kumar Kandala PhD
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    Genomics Orientations for Personalized Medicine (Frontiers in Genomics Research Book 1)

    Nov 22, 2015 | Kindle eBook

    by Sudipta Saha PhD and Ritu Saxena PhD
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    Metabolic Genomics & Pharmaceutics (BioMedicine – Metabolomics, Immunology, Infectious Diseases Book 1)

    Jul 21, 2015 | Kindle eBook

    by Larry H. Bernstein MD FCAP and Prabodah Kandala PhD
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    Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics (Series E: Patient-Centered Medicine Book 3)

    Dec 26, 2015 | Kindle eBook

    by Larry H. Bernstein MD FACP and Aviva Lev-Ari PhD RN
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    Regenerative and Translational Medicine: The Therapeutic Promise for Cardiovascular Diseases

    Dec 26, 2015 | Kindle eBook

    by Justin D. Pearlman MD ME PhD MA FACC and Ritu Saxena PhD
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    Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation: The Art of Scientific & Medical Curation

    Nov 29, 2015 | Kindle eBook

    by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RN
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Translation of whole human genome sequencing to clinical practice: The Joint Initiative for Metrology in Biology (JIMB) is a collaboration between the National Institute of Standards & Technology (NIST) and Stanford University.

Reporter: Aviva Lev-Ari, PhD, RN

 

JIMB’s mission is to advance the science of measuring biology (biometrology). JIMB is pursuing fundamental research, standards development, and the translation of products that support confidence in biological measurements and reliable reuse of materials and results. JIMB is particularly focused on measurements and technologies that impact, are related to, or enabled by ongoing advances in and associated with the reading and writing of DNA.

Stanford innovators and industry entrepreneurs have joined forces with the measurement experts from NIST to create a new engine powering the bioeconomy. It’s called JIMB — “Jim Bee” — the Joint Initiative for Metrology in Biology. JIMB unites people, platforms, and projects to underpin standards-based research and innovation in biometrology.

Genome in a Bottle
Authoritative Characterization of
Benchmark Human Genomes


The Genome in a Bottle Consortium is a public-private-academic consortium hosted by NIST to develop the technical infrastructure (reference standards, reference methods, and reference data) to enable translation of whole human genome sequencing to clinical practice. The priority of GIAB is authoritative characterization of human genomes for use in analytical validation and technology development, optimization, and demonstration. In 2015, NIST released the pilot genome Reference Material 8398, which is genomic DNA (NA12878) derived from a large batch of the Coriell cell line GM12878, characterized for high-confidence SNPs, indel, and homozygous reference regions (Zook, et al., Nature Biotechnology 2014).

There are four new GIAB reference materials available.  With the addition of these new reference materials (RMs) to a growing collection of “measuring sticks” for gene sequencing, we can now provide laboratories with even more capability to accurately “map” DNA for genetic testing, medical diagnoses and future customized drug therapies. The new tools feature sequenced genes from individuals in two genetically diverse groups, Asians and Ashkenazic Jews; a father-mother-child trio set from Ashkenazic Jews; and four microbes commonly used in research. For more information click here.  To purchase them, visit:

Data and analyses are publicly available (GIAB GitHub). A description of data generated by GIAB is published here. To standardize best practices for using GIAB genomes for benchmarking, we are working with the Global Alliance for Genomics and Health Benchmarking Team (benchmarking tools).

High-confidence small variant and homozygous reference calls are available for NA12878, the Ashkenazim trio, and the Chinese son with respect to GRCh37.  Preliminary high-confidence calls with respect to GRCh38 are also available for NA12878.   The latest version of these calls is under the latest directory for each genome on the GIAB FTP.

The consortium was initiated in a set of meetings in 2011 and 2012, and the consortium holds open, public workshops in January at Stanford University in Palo Alto, CA and in August/September at NIST in Gaithersburg, MD. Slides from workshops and conferences are available online. The consortium is open and welcomes new participants.

SOURCE

Stanford innovators and industry entrepreneurs have joined forces with the measurement experts from NIST to create a new engine powering the bioeconomy. It’s called JIMB — “Jim Bee” — the Joint Initiative for Metrology in Biology. JIMB unites people, platforms, and projects to underpin standards-based research and innovation in biometrology.

JIMB World Metrology Day Symposium

JIMB’s mission is to motivate standards-based measurement innovation to facilitate translation of basic science and technology development breakthroughs in genomics and synthetic biology.

By advancing biometrology, JIMB will push the boundaries of discovery science, accelerate technology development and dissemination, and generate reusable resources.

 SOURCE

VIEW VIDEO

https://player.vimeo.com/video/184956195?wmode=opaque&api=1″,”url”:”https://vimeo.com/184956195″,”width”:640,”height”:360,”providerName”:”Vimeo”,”thumbnailUrl”:”https://i.vimeocdn.com/video/594555038_640.jpg”,”resolvedBy”:”vimeo”}” data-block-type=”32″>

Other related articles published in this Open Access Online Scientific Journal include the following:

“Genome in a Bottle”: NIST’s new metrics for Clinical Human Genome Sequencing

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/06/genome-in-a-bottle-nists-new-metrics-for-clinical-human-genome-sequencing/

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Milestones in Physiology & Discoveries in Medicine and Genomics: Request for Book Review Writing on Amazon.com


physiology-cover-seriese-vol-3individualsaddlebrown-page2

Milestones in Physiology

Discoveries in Medicine, Genomics and Therapeutics

Patient-centric Perspective 

http://www.amazon.com/dp/B019VH97LU 

2015

 

 

Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com

Preface

Introduction 

Chapter 1: Evolution of the Foundation for Diagnostics and Pharmaceuticals Industries

1.1  Outline of Medical Discoveries between 1880 and 1980

1.2 The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century

1.3 The Classification of Microbiota

1.4 Selected Contributions to Chemistry from 1880 to 1980

1.5 The Evolution of Clinical Chemistry in the 20th Century

1.6 Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

 

Chapter 2. The search for the evolution of function of proteins, enzymes and metal catalysts in life processes

2.1 The life and work of Allan Wilson
2.2  The  evolution of myoglobin and hemoglobin
2.3  More complexity in proteins evolution
2.4  Life on earth is traced to oxygen binding
2.5  The colors of life function
2.6  The colors of respiration and electron transport
2.7  Highlights of a green evolution

 

Chapter 3. Evolution of New Relationships in Neuroendocrine States
3.1 Pituitary endocrine axis
3.2 Thyroid function
3.3 Sex hormones
3.4 Adrenal Cortex
3.5 Pancreatic Islets
3.6 Parathyroids
3.7 Gastointestinal hormones
3.8 Endocrine action on midbrain
3.9 Neural activity regulating endocrine response

3.10 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

 

Chapter 4.  Problems of the Circulation, Altitude, and Immunity

4.1 Innervation of Heart and Heart Rate
4.2 Action of hormones on the circulation
4.3 Allogeneic Transfusion Reactions
4.4 Graft-versus Host reaction
4.5 Unique problems of perinatal period
4.6. High altitude sickness
4.7 Deep water adaptation
4.8 Heart-Lung-and Kidney
4.9 Acute Lung Injury

4.10 Reconstruction of Life Processes requires both Genomics and Metabolomics to explain Phenotypes and Phylogenetics

 

Chapter 5. Problems of Diets and Lifestyle Changes

5.1 Anorexia nervosa
5.2 Voluntary and Involuntary S-insufficiency
5.3 Diarrheas – bacterial and nonbacterial
5.4 Gluten-free diets
5.5 Diet and cholesterol
5.6 Diet and Type 2 diabetes mellitus
5.7 Diet and exercise
5.8 Anxiety and quality of Life
5.9 Nutritional Supplements

 

Chapter 6. Advances in Genomics, Therapeutics and Pharmacogenomics

6.1 Natural Products Chemistry

6.2 The Challenge of Antimicrobial Resistance

6.3 Viruses, Vaccines and immunotherapy

6.4 Genomics and Metabolomics Advances in Cancer

6.5 Proteomics – Protein Interaction

6.6 Pharmacogenomics

6.7 Biomarker Guided Therapy

6.8 The Emergence of a Pharmaceutical Industry in the 20th Century: Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present

6.09 The Union of Biomarkers and Drug Development

6.10 Proteomics and Biomarker Discovery

6.11 Epigenomics and Companion Diagnostics

 

Chapter  7

Integration of Physiology, Genomics and Pharmacotherapy

7.1 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

7.2 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

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

7.4 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

7.5 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

7.6 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

7.7 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic drugs and Cholinesterase Inhibitors

7.8 Metabolite Identification Combining Genetic and Metabolic Information: Genetic association links unknown metabolites to functionally related genes

7.9 Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

7.10 Biosimilars: Intellectual Property Creation and Protection by Pioneer and by

7.11 Demonstrate Biosimilarity: New FDA Biosimilar Guidelines

 

Chapter 7.  Biopharma Today

8.1 A Great University engaged in Drug Discovery: University of Pittsburgh

8.2 Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

8.3 Predicting Tumor Response, Progression, and Time to Recurrence

8.4 Targeting Untargetable Proto-Oncogenes

8.5 Innovation: Drug Discovery, Medical Devices and Digital Health

8.6 Cardiotoxicity and Cardiomyopathy Related to Drugs Adverse Effects

8.7 Nanotechnology and Ocular Drug Delivery: Part I

8.8 Transdermal drug delivery (TDD) system and nanotechnology: Part II

8.9 The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

8.10 Natural Drug Target Discovery and Translational Medicine in Human Microbiome

8.11 From Genomics of Microorganisms to Translational Medicine

8.12 Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Homeostasis of Immune Responses for Good and Bad

 

Chapter 9. BioPharma – Future Trends

9.1 Artificial Intelligence Versus the Scientist: Who Will Win?

9.2 The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy

9.3 The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

9.4 Heroes in Medical Research: The Postdoctoral Fellow

9.5 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee

9.6 1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

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

9.8 Heroes in Medical Research: Green Fluorescent Protein and the Rough Road in Science

9.9 Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

9.10 The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

Epilogue

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genomicsinpersonalizedmedicinecovervolumeone

Content Consultant: Larry H Bernstein, MD, FCAP

Genomics Orientations for Personalized Medicine

Volume One

http://www.amazon.com/dp/B018DHBUO6

electronic Table of Contents

Chapter 1

1.1 Advances in the Understanding of the Human Genome The Initiation and Growth of Molecular Biology and Genomics – Part I

1.2 CRACKING THE CODE OF HUMAN LIFE: Milestones along the Way – Part IIA

1.3 DNA – The Next-Generation Storage Media for Digital Information

1.4 CRACKING THE CODE OF HUMAN LIFE: Recent Advances in Genomic Analysis and Disease – Part IIC

1.5 Advances in Separations Technology for the “OMICs” and Clarification of Therapeutic Targets

1.6 Genomic Analysis: FLUIDIGM Technology in the Life Science and Agricultural Biotechnology

Chapter 2

2.1 2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

2.2 DNA structure and Oligonucleotides

2.3 Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single Human Cell 

2.4 Genomics and Evolution

2.5 Protein-folding Simulation: Stanford’s Framework for Testing and Predicting Evolutionary Outcomes in Living Organisms – Work by Marcus Feldman

2.6 The Binding of Oligonucleotides in DNA and 3-D Lattice Structures

2.7 Finding the Genetic Links in Common Disease: Caveats of Whole Genome Sequencing Studies

Chapter 3

3.1 Big Data in Genomic Medicine

3.2 CRACKING THE CODE OF HUMAN LIFE: The Birth of Bioinformatics & Computational Genomics – Part IIB 

3.3 Expanding the Genetic Alphabet and linking the Genome to the Metabolome

3.4 Metabolite Identification Combining Genetic and Metabolic Information: Genetic Association Links Unknown Metabolites to Functionally Related Genes

3.5 MIT Scientists on Proteomics: All the Proteins in the Mitochondrial Matrix identified

3.6 Identification of Biomarkers that are Related to the Actin Cytoskeleton

3.7 Genetic basis of Complex Human Diseases: Dan Koboldt’s Advice to Next-Generation Sequencing Neophytes

3.8 MIT Team Researches Regulatory Motifs and Gene Expression of Erythroleukemia (K562) and Liver Carcinoma (HepG2) Cell Lines

Chapter 4

4.1 ENCODE Findings as Consortium

4.2 ENCODE: The Key to Unlocking the Secrets of Complex Genetic Diseases

4.3 Reveals from ENCODE Project will Invite High Synergistic Collaborations to Discover Specific Targets  

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

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

4.6 Quantum Biology And Computational Medicine

4.7 The Underappreciated EpiGenome

4.8 Unraveling Retrograde Signaling Pathways

4.9  “The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

4.10  DNA: One man’s trash is another man’s treasure, but there is no JUNK after all

Chapter 5

5.1 Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1 

5.2 Computational Genomics Center: New Unification of Computational Technologies at Stanford

5.3 Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3

5.4 Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz

5.5 Genome and Genetics: Resources @Stanford, @MIT, @NIH’s NCBCS

5.6 NGS Market: Trends and Development for Genotype-Phenotype Associations Research

5.7 Speeding Up Genome Analysis: MIT Algorithms for Direct Computation on Compressed Genomic Datasets

5.8  Modeling Targeted Therapy

5.9 Transphosphorylation of E-coli Proteins and Kinase Specificity

5.10 Genomics of Bacterial and Archaeal Viruses

Chapter 6

6.1  Directions for Genomics in Personalized Medicine

6.2 Ubiquinin-Proteosome pathway, Autophagy, the Mitochondrion, Proteolysis and Cell Apoptosis: Part III

6.3 Mitochondrial Damage and Repair under Oxidative Stress

6.4 Mitochondria: More than just the “Powerhouse of the Cell”

6.5 Mechanism of Variegation in Immutans

6.6 Impact of Evolutionary Selection on Functional Regions: The imprint of Evolutionary Selection on ENCODE Regulatory Elements is Manifested between Species and within Human Populations

6.7 Cardiac Ca2+ Signaling: Transcriptional Control

6.8 Unraveling Retrograde Signaling Pathways

6.9 Reprogramming Cell Fate

6.10 How Genes Function

6.11 TALENs and ZFNs

6.12 Zebrafish—Susceptible to Cancer

6.13 RNA Virus Genome as Bacterial Chromosome

6.14 Cloning the Vaccinia Virus Genome as a Bacterial Artificial Chromosome 

6.15 Telling NO to Cardiac Risk- DDAH Says NO to ADMA(1); The DDAH/ADMA/NOS Pathway(2)

6.16  Transphosphorylation of E-coli proteins and kinase specificity

6.17 Genomics of Bacterial and Archaeal Viruses

6.18  Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

Chapter 7

7.1 Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders @ http://pharmaceuticalintelligence.com

7.2 Consumer Market for Personal DNA Sequencing: Part 4

7.3 GSK for Personalized Medicine using Cancer Drugs Needs Alacris Systems Biology Model to Determine the In Silico Effect of the Inhibitor in its “Virtual Clinical Trial”

7.4 Drugging the Epigenome

7.5 Nation’s Biobanks: Academic institutions, Research institutes and Hospitals – vary by Collections Size, Types of Specimens and Applications: Regulations are Needed

7.6 Personalized Medicine: Clinical Aspiration of Microarrays

Chapter 8

8.1 Personalized Medicine as Key Area for Future Pharmaceutical Growth

8.2 Inaugural Genomics in Medicine – The Conference Program, 2/11-12/2013, San Francisco, CA

8.3 The Way With Personalized Medicine: Reporters’ Voice at the 8th Annual Personalized Medicine Conference, 11/28-29, 2012, Harvard Medical School, Boston, MA

8.4 Nanotechnology, Personalized Medicine and DNA Sequencing

8.5 Targeted Nucleases

8.6 Transcript Dynamics of Proinflammatory Genes

8.7 Helping Physicians identify Gene-Drug Interactions for Treatment Decisions: New ‘CLIPMERGE’ program – Personalized Medicine @ The Mount Sinai Medical Center

8.8 Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing[1]

8.9 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

Chapter 9

9.1 Personal Tale of JL’s Whole Genome Sequencing

9.2 Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics

9.3 Inform Genomics Developing SNP Test to Predict Side Effects, Help MDs Choose among Chemo Regimens

9.4 SNAP: Predict Effect of Non-synonymous Polymorphisms: How Well Genome Interpretation Tools could Translate to the Clinic

9.5  LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

9.6 The Initiation and Growth of Molecular Biology and Genomics – Part I

9.7 Personalized Medicine-based Cure for Cancer Might Not Be Far Away

9.8 Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)

 Chapter 10

10.1 Pfizer’s Kidney Cancer Drug Sutent Effectively caused REMISSION to Adult Acute Lymphoblastic Leukemia (ALL)

10.2 Imatinib (Gleevec) May Help Treat Aggressive Lymphoma: Chronic Lymphocytic Leukemia (CLL)

10.3 Winning Over Cancer Progression: New Oncology Drugs to Suppress Passengers Mutations vs. Driver Mutations

10.4 Treatment for Metastatic HER2 Breast Cancer

10.5 Personalized Medicine in NSCLC

10.6 Gene Sequencing – to the Bedside

10.7 DNA Sequencing Technology

10.8 Nobel Laureate Jack Szostak Previews his Plenary Keynote for Drug Discovery Chemistry

Chapter 11

11.1 mRNA Interference with Cancer Expression

11.2 Angiogenic Disease Research Utilizing microRNA Technology: UCSD and Regulus Therapeutics

11.3 Sunitinib brings Adult acute lymphoblastic leukemia (ALL) to Remission – RNA Sequencing – FLT3 Receptor Blockade

11.4 A microRNA Prognostic Marker Identified in Acute Leukemia 

11.5 MIT Team: Microfluidic-based approach – A Vectorless delivery of Functional siRNAs into Cells.

11.6 Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4

11.7 When Clinical Application of miRNAs?

11.8 How mobile elements in “Junk” DNA promote cancer. Part 1: Transposon-mediated tumorigenesis,

11.9 Potential Drug Target: Glycolysis Regulation – Oxidative Stress-responsive microRNA-320

11.10  MicroRNA Molecule May Serve as Biomarker

11.11 What about Circular RNAs?

Chapter 12

12.1 The “Cancer Establishments” Examined by James Watson, Co-discoverer of DNA w/Crick, 4/1953

12.2 Otto Warburg, A Giant of Modern Cellular Biology

12.3 Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

12.4 Hypothesis – Following on James Watson

12.5 AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo

12.6 AKT signaling variable effects

12.7 Rewriting the Mathematics of Tumor Growth; Teams Use Math Models to Sort Drivers from Passengers

12.8 Phosphatidyl-5-Inositol signaling by Pin1

Chapter 13

13.1 Nanotech Therapy for Breast Cancer

13.2 BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair

13.3 Exome sequencing of serous endometrial tumors shows recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes

13.4 Recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes in serous endometrial tumors

13.5 Prostate Cancer: Androgen-driven “Pathomechanism” in Early onset Forms of the Disease

13.6 In focus: Melanoma Genetics

13.7 Head and Neck Cancer Studies Suggest Alternative Markers More Prognostically Useful than HPV DNA Testing

13.8 Breast Cancer and Mitochondrial Mutations

13.9  Long noncoding RNA network regulates PTEN transcription

Chapter 14

14.1 HBV and HCV-associated Liver Cancer: Important Insights from the Genome

14.2 Nanotechnology and HIV/AIDS treatment

14.3 IRF-1 Deficiency Skews the Differentiation of Dendritic Cells

14.4 Sepsis, Multi-organ Dysfunction Syndrome, and Septic Shock: A Conundrum of Signaling Pathways Cascading Out of Control

14.5  Five Malaria Genomes Sequenced

14.6 Rheumatoid Arthritis Risk

14.7 Approach to Controlling Pathogenic Inflammation in Arthritis

14.8 RNA Virus Genome as Bacterial Chromosome

14.9 Cloning the Vaccinia Virus Genome as a Bacterial Artificial Chromosome

Chapter 15

15.1 Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School

15.2 Congestive Heart Failure & Personalized Medicine: Two-gene Test predicts response to Beta Blocker Bucindolol

15.3 DDAH Says NO to ADMA(1); The DDAH/ADMA/NOS Pathway(2)

15.4 Peroxisome Proliferator-Activated Receptor (PPAR-gamma) Receptors Activation: PPARγ Transrepression for Angiogenesis in Cardiovascular Disease and PPARγ Transactivation for Treatment of Diabetes

15.5 BARI 2D Trial Outcomes

15.6 Gene Therapy Into Healthy Heart Muscle: Reprogramming Scar Tissue In Damaged Hearts

15.7 Obstructive coronary artery disease diagnosed by RNA levels of 23 genes – CardioDx, a Pioneer in the Field of Cardiovascular Genomic  Diagnostics

15.8 Ca2+ signaling: transcriptional control

15.9 Lp(a) Gene Variant Association

15.9.1 Two Mutations, in the PCSK9 Gene: Eliminates a Protein involved in Controlling LDL Cholesterol

15.9.2. Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

15.9.3 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

15.9.4 The Implications of a Newly Discovered CYP2J2 Gene Polymorphism Associated with Coronary Vascular Disease in the Uygur Chinese Population

15.9.5  Gene, Meis1, Regulates the Heart’s Ability to Regenerate after Injuries.

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

15.11 How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancers?

Chapter 16

16.1 Can Resolvins Suppress Acute Lung Injury?

16.2 Lipoxin A4 Regulates Natural Killer Cell in Asthma

16.3 Biological Therapeutics for Asthma

16.4 Genomics of Bronchial Epithelial Dysplasia

16.5 Progression in Bronchial Dysplasia

Chapter 17

17.1 Breakthrough Digestive Disorders Research: Conditions Affecting the Gastrointestinal Tract.

17.2 Liver Endoplasmic Reticulum Stress and Hepatosteatosis

17.3 Biomarkers-identified-for-recurrence-in-hbv-related-hcc-patients-post-surgery

17.4  Usp9x: Promising Therapeutic Target for Pancreatic Cancer

17.5 Battle of Steve Jobs and Ralph Steinman with Pancreatic cancer: How We Lost

Chapter 18

18.1 Ubiquitin Pathway Involved in Neurodegenerative Disease

18.2 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

18.3 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic Drugs and Cholinesterase Inhibitors

18.4 Ustekinumab New Drug Therapy for Cognitive Decline Resulting from Neuroinflammatory Cytokine Signaling and Alzheimer’s Disease

18.5 Cell Transplantation in Brain Repair

18.6 Alzheimer’s Disease Conundrum – Are We Near the End of the Puzzle?

Chapter 19

19.1 Genetics and Male Endocrinology

19.2 Genomic Endocrinology and its Future

19.3 Commentary on Dr. Baker’s post “Junk DNA Codes for Valuable miRNAs: Non-coding DNA Controls Diabetes”

19.4 Therapeutic Targets for Diabetes and Related Metabolic Disorders

19.5 Secondary Hypertension caused by Aldosterone-producing Adenomas caused by Somatic Mutations in ATP1A1 and ATP2B3 (adrenal cortical; medullary or Organ of Zuckerkandl is pheochromocytoma)

19.6 Personal Recombination Map from Individual’s Sperm Cell and its Importance

19.7 Gene Trap Mutagenesis in Reproductive Research

19.8 Pregnancy with a Leptin-Receptor Mutation

19.9 Whole-genome Sequencing in Probing the Meiotic Recombination and Aneuploidy of Single Sperm Cells

19.10 Reproductive Genetic Testing

Chapter 20

20.1 Genomics & Ethics: DNA Fragments are Products of Nature or Patentable Genes?

20.2 Understanding the Role of Personalized Medicine

20.3 Attitudes of Patients about Personalized Medicine

20.4  Genome Sequencing of the Healthy

20.5   Genomics in Medicine – Tomorrow’s Promise

20.6  The Promise of Personalized Medicine

20.7 Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk

 20.8 Genomic Liberty of Ownership, Genome Medicine and Patenting the Human Genome

Chapter 21

Recent Advances in Gene Editing Technology Adds New Therapeutic Potential for the Genomic Era:  Medical Interpretation of the Genomics Frontier – CRISPR – Cas9

Introduction

21.1 Introducing CRISPR/Cas9 Gene Editing Technology – Works by Jennifer A. Doudna

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

21.1.2 Evaluate your Cas9 gene editing vectors: CRISPR/Cas Mediated Genome Engineering – Is your CRISPR gRNA optimized for your cell lines?

21.1.3 2:15 – 2:45, 6/13/2014, Jennifer Doudna “The biology of CRISPRs: from genome defense to genetic engineering”

21.1.4  Prediction of the Winner RNA Technology, the FRONTIER of SCIENCE on RNA Biology, Cancer and Therapeutics  & The Start Up Landscape in BostonGene Editing – New Technology The Missing link for Gene Therapy?

21.2 CRISPR in Other Labs

21.2.1 CRISPR @MIT – Genome Surgery

21.2.2 The CRISPR-Cas9 System: A Powerful Tool for Genome Engineering and Regulation

Yongmin Yan and Department of Gastroenterology, Hepatology & Nutrition, University of Texas M.D. Anderson Cancer, Houston, USADaoyan Wei*

21.2.3 New Frontiers in Gene Editing: Transitioning From the Lab to the Clinic, February 19-20, 2015 | The InterContinental San Francisco | San Francisco, CA

21.2.4 Gene Therapy and the Genetic Study of Disease: @Berkeley and @UCSF – New DNA-editing technology spawns bold UC initiative as Crispr Goes Global

21.2.5 CRISPR & MAGE @ George Church’s Lab @ Harvard

21.3 Patents Awarded and Pending for CRISPR

21.3.1 Litigation on the Way: Broad Institute Gets Patent on Revolutionary Gene-Editing Method

21.3.2 The Patents for CRISPR, the DNA editing technology as the Biggest Biotech Discovery of the Century

2.4 CRISPR/Cas9 Applications

21.4.1  Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells using a bacterial CRISPR/Cas 

21.4.2 CRISPR: Applications for Autoimmune Diseases @UCSF

21.4.3 In vivo validated mRNAs

21.4.6 Level of Comfort with Making Changes to the DNA of an Organism

21.4.7 Who will be the the First to IPO: Novartis bought in to Intellia (UC, Berkeley) as well as Caribou (UC, Berkeley) vs Editas (MIT)??

21.4.8 CRISPR/Cas9 Finds Its Way As an Important Tool For Drug Discovery & Development

Summary

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Pathophysiology in Hypertension: Opposing Roles of Human Adaptive Immunity

Reporter: Aviva Lev-Ari, PhD, RN

T regulatory lymphocytes counteract hypertensive effects by suppressing innate and adaptive immune responses and T effector lymphocytes promote differentiation towards pro-inflammatory T helper cells

 

Dual opposing roles of adaptive immunity in hypertension

 

, , ,

DOI: http://dx.doi.org/10.1093/eurheartj/ehu119 1238-1244 First published online: 30 March 2014

Abstract

Hypertension involves remodelling and inflammation of the arterial wall. Interactions between vascular and inflammatory cells play a critical role in disease initiation and progression. T effector and regulatory lymphocytes, members of the adaptive immune system, play contrasting roles in hypertension. Signals from the central nervous system and the innate immune system antigen-presenting cells activate T effector lymphocytes and promote their differentiation towards pro-inflammatory T helper (Th) 1 and Th17 phenotypes. Th1 and Th17 effector cells, via production of pro-inflammatory mediators, participate in the low-grade inflammation that leads to blood pressure elevation and end-organ damage. T regulatory lymphocytes, on the other hand, counteract hypertensive effects by suppressing innate and adaptive immune responses. The present review summarizes and discusses the adaptive immune mechanisms that participate in the pathophysiology in hypertension.

  • Blood pressure
  • Adaptive immunity
  • Inflammation
  • T effector lymphocytes
  • T regulatory lymphocytes
  • Cytokines

Conclusion

Experimental and clinical evidence discussed in this review strongly suggests that adaptive immunity, represented by T effector and regulatory lymphocyte subsets, plays a dual role in hypertension (Figure 2). Increased sympathetic outflow as a consequence of stimulation of the CNS by hypertensive stimuli may result in mild blood pressure elevation, causing tissue injury and formation of neoantigens2 and/or damage-associated molecular patterns (DAMPs).80 Activation of innate APCs by DAMPs, or by pathogen-associated molecular patterns (PAMPs) generated in response to low-grade infection,80,81 and direct stimulation by CNS, may be the cause of activation of CD4+, and perhaps CD8+, T effector lymphocytes, and differentiation of CD4+ T cells towards pro-inflammatory Th1/Th17 phenotypes.41 Th1/Th17 effector lymphocytes contribute to the progression of hypertension by producing pro-inflammatory mediators, including ROS, IFN-γ, TNF-α, and IL-17, to promote low-grade inflammation.24,41,42,51,52 T regulatory lymphocytes, on the other hand, counteract hypertensive abnormalities by suppressing innate and adaptive immune responses, perhaps by secreting IL-10.6571 As such, circulating levels of Tregs or their immune-suppressive activity may be affected in hypertension.

 SOURCE

http://eurheartj.oxfordjournals.org/content/35/19/1238

Idris-Khodja et al. (2014) Dual opposing roles of adaptive immunity in hypertension. European Heart Journal (doi: 10.1093/eurheartj/ehu119)

 

Adaptive Immunity

Figure 1

Differentiation of naïve T lymphocytes into various subsets in a normal immune response. Antigen-presenting cells (dendritic cells and monocyte/macrophages) present antigens on major histocompatibility complex (MHC)-II to naïve T cells (Th0) in secondary lymphoid tissues, leading to T-cell clonal expansion and differentiation into effector T cells, such as T helper (Th)1, Th2, and Th17 or T regulatory (Treg) cells according to combined stimulation by different cytokines. Th effector lymphocytes and Tregs migrate into tissues such as the vasculature, particularly at the level of the adventitia and perivascular fat. The effector lymphocytes (Th1 and Th17) cells activate other immune cells and participate in inflammation by producing pro-inflammatory cytokines such as interferon-γ, interleukin (IL)-6, and IL-17. T regulatory lymphocytes suppress innate and adaptive responses via production of anti-inflammatory cytokines IL-10 and transforming growth factor-β. CD, cluster of differentiation; DC, dendritic cell; MΦ, macrophage; NK cell, natural killer cell; Tc, cytotoxic T cell; TCR, T-cell receptor.

IMAGE SOURCE

http://eurheartj.oxfordjournals.org/content/35/19/1238

 

Hypertention

 

IMAGE SOURCE

http://eurheartj.oxfordjournals.org/content/35/19/1238

Figure 2

Proposed role of T effector and regulatory lymphocytes in hypertension. Slight elevation in blood pressure (BP) in response to hypertensive stimuli (angiotensin II, aldosterone, endothelin-1, salt and genetic susceptibility) occurs due to increased central signalling, perhaps causing mild tissue injury and formation of damage-associated molecular patterns (DAMPs) and neoantigens. This may lead to activation of innate antigen-presenting cells (APCs) and, subsequently, activation and polarization of naïve CD4+ T effector lymphocytes (Th0) towards pro-inflammatory T helper (Th)1/Th17 phenotypes. Th1/Th17 may contribute to vascular and kidney damage via production of reactive oxygen species (ROS), interferon (IFN)-γ and interleukin (IL)-17 and lead to maintenance of hypertension and progression of end-organ damage. T regulatory lymphocytes counteract hypertension and associated injury by producing IL-10 or by other mechanisms, and suppression of innate and adaptive immune responses. CD, cluster of differentiation; CNS, central nervous system; MHC-II, major histocompatibility complex-II; PAMPs, pathogen-associated molecular patterns; TCR, T-cell receptor.

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