Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Archive for the ‘Bio Instrumentation in Experimental Life Sciences Research’ Category

Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Posted in Acute Myocardial Infarction, Adaptive Immune Response to Biomaterials and Tissue Repair, Advanced Drug Manufacturing Technology, Amino acids, Apoptosis, Apoptosis, Artificial intelligence applications for cardiology, Artificial Intelligence in Medicine - Application for Diagnosis, Artificial Intelligence in Medicine - Applications in Therapeutics, Atherogenic Processes & Pathology, Autoimmune Inflammatory DIseases, Autologous Cell Therapy, Automated Cell Processing, Autophagosome, Autophagy, Autophagy-Modulating Proteins, “Antibody–enzyme conjugates”, Bio Instrumentation in Experimental Life Sciences Research, Biochemical pathways, Bioengineering & reverse engineering design, Biological Engineering, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Ca2+ triggered activation, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cancer - General, Cardiac muscle regeneration, Cardiovascular Pharmacogenomics, Cell Biology, Signaling & Cell Circuits, Cell death pathways, Cell Processing System in Cell Therapy Process Development, Cerebrovascular and Neurodegenerative Diseases, Chemical Biology and its relations to Metabolic Disease, children, Clinical & Translational, Clinical Genomics, Computational Histopathology, congestive heart failure, Cytokine Receptor Structure, Cytokines, Deep Learning in Pathology, Dehydrogenase, Developmental biology, Diabetes Mellitus, Diagnostic Immunology, Disease Biology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Carrier Design, Drug Delivery Platform Technology, Drug Discovery Chemistry, drug repurposing, Endocrine Diseases, Endoplasmic reticulum, Enzyme Induction, Enzymes and isoenzymes, Epigenetics and Cardiovascular Risks, Epigenetics and Environmental Factors, Evolution of Biology Through Culture, Fatty acids, Frontiers in Cardiology and Cardiovascular Disorders, Gastroenterology, Gene Regulation, Genome Biology, Genomic Analysis of EKG Electrophysiology Genomics, Genomic Endocrinology, Genomics Pharmacy, Glycobiology: Biopharmaceutical Production, Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics, Gut Microbiome and Obesity, HTN, HTN in Youth, Human Antibody Response, Human Circulating Antibody Repertoire, Human Immune System in Health and in Disease, Human Sensation and Cellular Transduction: Physiology and Therapeutics, Immuno-Oncology & Genomics, Immunodiagnostics, Immunology, Immunotherapy, Indigent Nutrition, inflammation independent of lipid levels, Inflammatory Pathophysiology, Innovation in Immunology Diagnostics, Inosine nucleotides, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Interviews with Scientific Leaders, Investment in Technological Breakthrough, ion-transporting enzyme, IP Development by LPBI Group Team, Kinase, Lipid metabolism, Lipidomics, Lipids, Liposome, Liver & Digestive Diseases Research, Machine learning in predicting type 2 diabetes, Materials Science & Engineering, Medical and Population Genetics, Meta-analysis of transcriptome data, Metabolism, Metabolomics, Methylation, Microbiologial genetics, microbiome, Microfuidics, Micronutrients, Microvesicle, Molecular Genetics & Pharmaceutical, Mutant Gene Expression, Myocardial adenine nucleotide metabolism, Myocardial Ischemia, Myocardial Metabolism, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Na-K transport, Na-K-ATPase, Nanotechnology for Drug Delivery, Neurodegenerative Diseases, Neurohumoral Transmission, Neurological Diseases, Nitric Oxide in Health and Disease, Nutrigenomics, Nutrition, Nutrition and Phytochemistry, Nutrition Disorders, Nutritional Supplements: Atherogenesis, Nutritional Supplements: Atherogenesis, lipid metabolism, Obesity, Organic BioElectronics, Origins of Cardiovascular Disease, Pancreatic adenocarcinoma classifier, Patient-centered Medicine, Perioperative Statins at Noncardiac Surgery, Personalized and Precision Medicine & Genomic Research, Phagophore, Pharmaceutical Analytics, Pharmaceutical Drug Discovery, Pharmacodynamics and Pharmacokinetics, Pharmacogenomics, Pharmacotherapy and Cell Activity, Pharmacotherapy of Cardiovascular Disease, Phosphatase, Phosphorylase, Phosphorylation, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Precision Cancer Medicine, Protection Against Autoimmune Disease, Protein-energy malnutrition, Proteins, Proteomics, Rare heart rhythm disorders and Long QT syndrome (LQTS), Regenerative Biology and Medicine, RNA Biology, S-nitrosylation, Sensors & Analytics, Signaling, Signaling & Cell Circuits, single cell sequencing, Skeletal muscle regeneration, Small Molecules in Development of Therapeutic Drugs, Statistical Methods for Research Evaluation, Stress Disorders, Stroke, Stroke, Systemic Inflammatory Diseases as CVD Risk, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, therapeutics, Tissue Engineering and Regenerative Medicine, Tissue Microenvironment, Tolerance-inducing Autoimmune Disease Therapeutics, Transcriptomics, Transformative Technologies in Healthcare, Translational Research, tyrosine decarboxylases, Ubiquitin, Ubiquitinylation, Unfolded Protein Response (UPR), Universal Immune Cell Therapies (uICT), Variation in human protein-coding regions, Vascular Diseases, Water Transporters on August 19, 2023| Leave a Comment »

Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use

Curators:

• Cardiovascular Expertise – Dr. Justin D. Pearlman, MD, PhD, FACC
• Pharmacology and Oncology Expertise – Dr. Stephen J. Williams, PhD
• Principal Investigator, initiator of the project – Aviva Lev-Ari, PhD, RN

 

THE VOICE of Aviva Lev-Ari, PhD, RN

In this curation we wish to present two breaking through goals:

Goal 1:

Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer

Goal 2:

Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.

According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.

These eight subcellular pathologies can’t be measured at present time.

In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.

Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases

1. Glycation
2. Oxidative Stress
3. Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
4. Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
5. Membrane instability
6. Inflammation in the gut [mucin layer and tight junctions]
7. Epigenetics/Methylation
8. Autophagy [AMPKbeta1 improvement in health span]

Diseases that are not Diseases: no drugs for them, only diet modification will help

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

Exercise will not undo Unhealthy Diet

Image source

Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease

https://www.youtube.com/watch?v=Ee_uoxuQo0I

 

These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:

1. Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
2. IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL

In the Bioelecronics domain we are inspired by the work of the following three research sources:

1. Biological and Biomedical Electrical Engineering (B2E2) at Cornell University, School of Engineering https://www.engineering.cornell.edu/bio-electrical-engineering-0
2. Bioelectronics Group at MIT https://bioelectronics.mit.edu/
3. The work of Michael Levin @Tufts, The Levin Lab

Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia

Born: 1969 (age 54 years), Moscow, Russia

Education: Harvard University (1992–1996), Tufts University (1988–1992)

Affiliation: University of Cape Town

Research interests: Allergy, Immunology, Cross Cultural Communication

Awards: Cozzarelli prize (2020)

Doctoral advisor: Clifford Tabin

Fields: Developmental biology, synthetic biology

SOURCE

https://www.google.com/search?q=Michael+Levin+%40Tufts&oq=Michael+Levin+%40Tufts&aqs=chrome..69i57j69i58.894128314j0j15&sourceid=chrome&ie=UTF-8

Most recent 20 Publications by Michael Levin, PhD

SOURCE

https://facultyprofiles.tufts.edu/michael-levin-1/publications

SCHOLARLY ARTICLE

The nonlinearity of regulation in biological networks

1 Dec 2023npj Systems Biology and Applications9(1)

Co-authorsManicka S, Johnson K, Levin M…1 more

VIEW PDF10.1038/S41540-023-00273-W

3

SCHOLARLY ARTICLE

Toward an ethics of autopoietic technology: Stress, care, and intelligence

1 Sep 2023BioSystems231

Co-authorsWitkowski O, Doctor T, Solomonova E…2 more

VIEW PDF10.1016/J.BIOSYSTEMS.2023.104964

SCHOLARLY ARTICLE

Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion

14 Aug 2023Frontiers in Cell and Developmental Biology11:1087650

Co-authorsGrodstein J, McMillen P, Levin M

VIEW PDF10.3389/FCELL.2023.1087650

SCHOLARLY ARTICLE

Correcting instructive electric potential patterns in multicellular systems: External actions and endogenous processes.

30 Jul 2023Biochim Biophys Acta Gen Subj1867(10):130440

Co-authorsCervera J, Levin M, Mafe S

VIEW MORE INFO10.1016/J.BBAGEN.2023.130440

SCHOLARLY ARTICLE

Regulative development as a model for origin of life and artificial life studies

1 Jul 2023BioSystems229

Co-authorsFields C, Levin M

10.1016/J.BIOSYSTEMS.2023.104927

1

SCHOLARLY ARTICLE

The Yin and Yang of Breast Cancer: Ion Channels as Determinants of Left–Right Functional Differences

1 Jul 2023International Journal of Molecular Sciences24(13)

Co-authorsMasuelli S, Real S, McMillen P…3 more

VIEW PDF10.3390/IJMS241311121

SCHOLARLY ARTICLE

Bioelectricidad en agregados multicelulares de células no excitables- modelos biofísicos

Jun 2023Revista Española de Física32(2)

Co-authorsCervera J, Levin M, Mafé S

SCHOLARLY ARTICLE

Bioelectricity: A Multifaceted Discipline, and a Multifaceted Issue!

1 Jun 2023Bioelectricity5(2):75

Co-authorsDjamgoz MBA, Levin M

10.1089/BIOE.2023.0022.EDITORIAL

SCHOLARLY ARTICLE

Control Flow in Active Inference Systems – Part I: Classical and Quantum Formulations of Active Inference

1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):235-245

Co-authorsFields C, Fabrocini F, Friston K…4 more

10.1109/TMBMC.2023.3272150

2

SCHOLARLY ARTICLE

Control Flow in Active Inference Systems – Part II: Tensor Networks as General Models of Control Flow

1 Jun 2023IEEE Transactions on Molecular, Biological, and Multi-Scale Communications9(2):246-256

Co-authorsFields C, Fabrocini F, Friston K…4 more

10.1109/TMBMC.2023.3272158

2

SCHOLARLY ARTICLE

Darwin’s agential materials: evolutionary implications of multiscale competency in developmental biology

1 Jun 2023Cellular and Molecular Life Sciences80(6)

Co-authorsLevin M

VIEW PDF10.1007/S00018-023-04790-Z

1

SCHOLARLY ARTICLE

Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

1 Jun 2023Drug Discovery Today28(6)

Co-authorsPio-Lopez L, Levin M

VIEW PDF10.1016/J.DRUDIS.2023.103585

1

SCHOLARLY ARTICLE

Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

Jun 2023DRUG DISCOVERY TODAY28(6):1-13

Co-authorsPio-Lopez L, Levin M

VIEW MORE INFO10.1016/J.DRUDIS.2023.103585THIS

SCHOLARLY ARTICLE

Cellular signaling pathways as plastic, proto-cognitive systems: Implications for biomedicine

12 May 2023Patterns4(5)

Co-authorsMathews J, Chang A, Devlin L…1 more

VIEW PDF10.1016/J.PATTER.2023.100737

3

SCHOLARLY ARTICLE

Making and breaking symmetries in mind and life

14 Apr 2023Interface Focus13(3)

Co-authorsSafron A, Sakthivadivel DAR, Sheikhbahaee Z…3 more

VIEW PDF10.1098/RSFS.2023.0015

SCHOLARLY ARTICLE

The scaling of goals from cellular to anatomical homeostasis: an evolutionary simulation, experiment and analysis

14 Apr 2023Interface Focus13(3)

Co-authorsPio-Lopez L, Bischof J, LaPalme JV…1 more

VIEW PDF10.1098/RSFS.2022.0072

1

SCHOLARLY ARTICLE

The collective intelligence of evolution and development

Apr 2023Collective Intelligence2(2):263391372311683SAGE Publications

Co-authorsWatson R, Levin M

VIEW PDF10.1177/26339137231168355

SCHOLARLY ARTICLE

Bioelectricity of non-excitable cells and multicellular pattern memories: Biophysical modeling

13 Mar 2023Physics Reports1004:1-31

Co-authorsCervera J, Levin M, Mafe S

10.1016/J.PHYSREP.2022.12.003

2

SCHOLARLY ARTICLE

There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-Scale Machines

1 Mar 2023Biomimetics8(1)

Co-authorsBongard J, Levin M

VIEW PDF10.3390/BIOMIMETICS8010110

4

SCHOLARLY ARTICLE

Transplantation of fragments from different planaria: A bioelectrical model for head regeneration

7 Feb 2023Journal of Theoretical Biology558

Co-authorsCervera J, Manzanares JA, Levin M…1 more

VIEW PDF10.1016/J.JTBI.2022.111356

SCHOLARLY ARTICLE

Bioelectric networks: the cognitive glue enabling evolutionary scaling from physiology to mind

1 Jan 2023Animal Cognition

Co-authorsLevin M

VIEW PDF10.1007/S10071-023-01780-3

2

SCHOLARLY ARTICLE

Biological Robots: Perspectives on an Emerging Interdisciplinary Field

1 Jan 2023Soft Robotics

Co-authorsBlackiston D, Kriegman S, Bongard J…1 more

10.1089/SORO.2022.0142

1

SCHOLARLY ARTICLE

Cellular Competency during Development Alters Evolutionary Dynamics in an Artificial Embryogeny Model

1 Jan 2023Entropy25(1)

Co-authorsShreesha L, Levin M

VIEW PDF10.3390/E25010131

5

SCHOLARLY ARTICLE

Endless forms most beautiful 2.0: teleonomy and the bioengineering of chimaeric and synthetic organisms (July, blac073, 2022)

1 Jan 2023BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY138(1):141

Co-authorsClawson WP, Levin M

VIEW PDFVIEW MORE INFO10.1093/BIOLINNEAN/BLAC116

SCHOLARLY ARTICLE

Future medicine: from molecular pathways to the collective intelligence of the body

1 Jan 2023Trends in Molecular Medicine

Co-authorsLagasse E, Levin M

10.1016/J.MOLMED.2023.06.007

THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC

PENDING

THE VOICE of  Stephen J. Williams, PhD

Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes

 

1. 25% of US children have fatty liver
2. Type II diabetes can be manifested from fatty live with 151 million  people worldwide affected moving up to 568 million in 7 years
3. A common myth is diabetes due to overweight condition driving the metabolic disease
4. There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
5. Thirty percent of ‘obese’ people just have high subcutaneous fat.  the visceral fat is more problematic
6. there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects.  Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
7. At any BMI some patients are insulin sensitive while some resistant
8. Visceral fat accumulation may be more due to chronic stress condition
9. Fructose can decrease liver mitochondrial function
10. A methionine and choline deficient diet can lead to rapid NASH development

 

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

Accelerating PROTAC drug discovery: Establishing a relationship between ubiquitination and target protein degradation

Posted in Apoptosis, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Biomedical Measurement Science, Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Childhood cancer, Enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP), KRAS Mutation, Li-fraumeni syndrome., Proteosome, TP53 - Germline mutations, Ubiquitin, tagged breast cancer, Cancer - General, E3 Ligase, high throughput, MDM2, PROTAC, TUBEs, Ubiquitin ligase, ubiquitin-proteosome, VHL on October 4, 2022| Leave a Comment »

Accelerating PROTAC drug discovery: Establishing a relationship between ubiquitination and target protein degradation

Curator: Stephen J. Williams, Ph.D.

PROTACs have been explored in multiple disease fields with focus on only few ligases like cereblon (CRBN), Von Hippel-Lindau (VHL), IAP and MDM2. Cancer targets like androgen receptor, estrogen receptor, BTK, BCL2, CDK8 and c-MET [[6], [7], [8], [9], [10], [11]] have been successfully targeted using PROTACs. A variety of BET family (BRD2, BRD3, and BRD4)- PROTACs were designed using multiple ligases; MDM2-based BRD4 PROTAC [12], CRBN based dBET1 [13] and BETd-24-6 [14] for triple-negative breast cancer, enhanced membrane permeable dBET6 [15], and dBET57 PROTAC [16]. PROTACs for Hepatitis c virus (HCV) protease, IRAK4 and Tau [[17], [18], [19]] have been explored for viral, immune and neurodegenerative diseases, respectively. Currently, the PROTAC field expansion to vast undruggable proteome is hindered due to narrow focus on select E3 ligases. Lack of reliable tools to rapidly evaluate PROTACs based on new ligases is hindering the progress. Screening platforms designed must be physiologically relevant and represent true PROTAC cellular function, i.e., PROTAC-mediated target ubiquitination and degradation.

In the current study, we employ TUBEs as affinity capture reagents to monitor PROTAC-induced poly-ubiquitination and degradation as a measure of potency. We established and validated proof-of-concept cell-based assays in a 96-well format using PROTACS for three therapeutic targets BET family proteins, kinases, and KRAS. To our knowledge, the proposed PROTAC assays are first of its kind that can simultaneously 1) detect ubiquitination of endogenous, native protein targets, 2) evaluate the potency of PROTACs, and 3) establish a link between the UPS and protein degradation. Using these TUBE assays, we established rank order potencies between four BET family PROTACs dBET1, dBET6, BETd246 and dBET57 based on peak ubiquitination signals (“Ub_Max”) of the target protein. TUBE assay was successful in demonstrating promiscuous kinase PROTACs efficiency to degrade Aurora Kinase A at sub-nanomolar concentrations within 1 h. A comparative study to identify changes in the ubiquitination and degradation profile of KRAS G12C PROTACs recruiting two E3 ligases (CRBN and VHL). All of the ubiquitination and degradation profiles obtained from TUBE based assays correlate well with traditional low throughput immunoblotting. Significant correlation between DC₅₀ obtained from protein degradation in western blotting and Ub_Max values demonstrates our proposed assays can aid in high-throughput screening and drastically eliminate artifacts to overcome bottlenecks in PROTAC drug discovery.

To successfully set up HTS screening with novel PROTACs without pre-existing knowledge, we recommend the following steps. 1. Identify a model PROTAC that can potentially demonstrate activity based on knowledge in PROTAC design or in vitro binding studies. 2. Perform a time course study with 2–3 doses of the model PROTAC based on affinities of the ligands selected. 3. Monitor ubiquitination and degradation profiles using plate-based assay and identify time point that demonstrates Ub_Max. 4. Perform a dose response at selected time point with a library of PROTACs to establish rank order potency.

INTRODUCTION

Ubiquitination is a major regulatory mechanism to maintain cellular protein homeostasis by marking proteins for proteasomal-mediated degradation [1]. Given ubiquitin’s role in a variety of pathologies, the idea of targeting the Ubiquitin Proteasome System (UPS) is at the forefront of drug discovery [2]. “Event-driven” protein degradation using the cell’s own UPS is a promising technology for addressing the “undruggable” proteome [3]. Targeted protein degradation (TPD) has emerged as a new paradigm and promising therapeutic option to selectively attack previously intractable drug targets using PROteolytic TArgeting Chimeras (PROTACs) [4]. PROTACs are heterobifunctional molecules with a distinct ligand that targets a specific E3 ligase which is tethered to another ligand specific for the target protein using an optimized chemical linker. A functional PROTAC induces a ternary E3-PROTAC-target complex, resulting in poly-ubiquitination and subsequent controlled protein degradation [5]. Ability to function at sub-stoichiometric levels for efficient degradation, a significant advantage over traditional small molecules.

PROTACs have been explored in multiple disease fields with focus on only few ligases like cereblon (CRBN), Von Hippel-Lindau (VHL), IAP and MDM2. Cancer targets like androgen receptor, estrogen receptor, BTK, BCL2, CDK8 and c-MET [[6], [7], [8], [9], [10], [11]] have been successfully targeted using PROTACs. A variety of BET family (BRD2, BRD3, and BRD4)- PROTACs were designed using multiple ligases; MDM2-based BRD4 PROTAC [12], CRBN based dBET1 [13] and BETd-24-6 [14] for triple-negative breast cancer, enhanced membrane permeable dBET6 [15], and dBET57 PROTAC [16]. PROTACs for Hepatitis c virus (HCV) protease, IRAK4 and Tau [[17], [18], [19]] have been explored for viral, immune and neurodegenerative diseases, respectively. Currently, the PROTAC field expansion to vast undruggable proteome is hindered due to narrow focus on select E3 ligases. Lack of reliable tools to rapidly evaluate PROTACs based on new ligases is hindering the progress. Screening platforms designed must be physiologically relevant and represent true PROTAC cellular function, i.e., PROTAC-mediated target ubiquitination and degradation.

Cellular PROTAC screening is traditionally performed using cell lines harboring reporter genes and/or Western blotting. While Western blotting is easy to perform, they are low throughput, semi-quantitative and lack sensitivity. While reporter gene assays address some of the issues, they are challenged by reporter tags having internal lysines leading to artifacts. Currently, no approaches are available that can identify true PROTAC effects such as target ubiquitination and proteasome-mediated degradation simultaneously. High affinity ubiquitin capture reagents like TUBEs [20] (tandem ubiquitin binding entities), are engineered ubiquitin binding domains (UBDs) that allow for detection of ultralow levels of polyubiquitinated proteins under native conditions with affinities as low as 1 nM. The versatility and selectivity of TUBEs makes them superior to antibodies, and they also offer chain-selectivity (-K48, -K63, or linear) [21]. High throughput assays that can report the efficacy of multiple PROTACs simultaneously by monitoring PROTAC mediated ubiquitination can help establish rank order potency and guide chemists in developing meaningful structure activity relationships (SAR) rapidly.

In the current study, we employ TUBEs as affinity capture reagents to monitor PROTAC-induced poly-ubiquitination and degradation as a measure of potency. We established and validated proof-of-concept cell-based assays in a 96-well format using PROTACS for three therapeutic targets BET family proteins, kinases, and KRAS. To our knowledge, the proposed PROTAC assays are first of its kind that can simultaneously 1) detect ubiquitination of endogenous, native protein targets, 2) evaluate the potency of PROTACs, and 3) establish a link between the UPS and protein degradation. Using these TUBE assays, we established rank order potencies between four BET family PROTACs dBET1, dBET6, BETd246 and dBET57 based on peak ubiquitination signals (“Ub_Max”) of the target protein. TUBE assay was successful in demonstrating promiscuous kinase PROTACs efficiency to degrade Aurora Kinase A at sub-nanomolar concentrations within 1 h. A comparative study to identify changes in the ubiquitination and degradation profile of KRAS G12C PROTACs recruiting two E3 ligases (CRBN and VHL). All of the ubiquitination and degradation profiles obtained from TUBE based assays correlate well with traditional low throughput immunoblotting. Significant correlation between DC₅₀ obtained from protein degradation in western blotting and Ub_Max values demonstrates our proposed assays can aid in high-throughput screening and drastically eliminate artifacts to overcome bottlenecks in PROTAC drug discovery.

 

 

 

 

 

 

 

 

 

SOURCE

https://www.sciencedirect.com/science/article/abs/pii/S0006291X22011792

Other articles of PROTACs in this Open Access Journal Include

The Vibrant Philly Biotech Scene: Proteovant Therapeutics Using Artificial Intelligence and Machine Learning to Develop PROTACs

The Map of human proteins drawn by artificial intelligence and PROTAC (proteolysis targeting chimeras) Technology for Drug Discovery

Live Conference Coverage AACR 2020 in Real Time: Monday June 22, 2020 Late Day Sessions

From High-Throughput Assay to Systems Biology: New Tools for Drug Discovery

 

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

The Human Genome Gets Fully Sequenced: A Simplistic Take on Century Long Effort

Posted in Big Data, Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biological Networks, Gene Regulation and Evolution, Disease Biology, Genome Biology, Next Generation Sequencing (NGS), Nobel Prize Winners, Single-cell sequencing, Variation in human protein-coding regions, tagged AAAS, Craig Venter, DNA Sequencing, genetic variants, Human Genome Project, Jennifer Doudna, junk DNA, telomere consortium on June 14, 2022| Leave a Comment »

The Human Genome Gets Fully Sequenced: A Simplistic Take on Century Long Effort

 

Curator: Stephen J. Williams, PhD

Article ID #295: The Human Genome Gets Fully Sequenced: A Simplistic Take on Century Long Effort. Published on 6/14/2022

WordCloud Image Produced by Adam Tubman

Ever since the hard work by Rosalind Franklin to deduce structures of DNA and the coincidental work by Francis Crick and James Watson who modeled the basic building blocks of DNA, DNA has been considered as the basic unit of heredity and life, with the “Central Dogma” (DNA to RNA to Protein) at its core.  These were the discoveries in the early twentieth century, and helped drive the transformational shift of biological experimentation, from protein isolation and characterization to cloning protein-encoding genes to characterizing how the genes are expressed temporally, spatially, and contextually.

Rosalind Franklin, who’s crystolagraphic data led to determination of DNA structure. Shown as 1953 Time cover as Time person of the Year

Dr Francis Crick and James Watson in front of their model structure of DNA

 

 

 

 

 

 

 

 

 

Up to this point (1970s-mid 80s) , it was felt that genetic information was rather static, and the goal was still to understand and characterize protein structure and function while an understanding of the underlying genetic information was more important for efforts like linkage analysis of genetic defects and tools for the rapidly developing field of molecular biology.  But the development of the aforementioned molecular biology tools including DNA cloning, sequencing and synthesis, gave scientists the idea that a whole recording of the human genome might be possible and worth the effort.

How the Human Genome Project  Expanded our View of Genes Genetic Material and Biological Processes

 

 

From the Human Genome Project Information Archive

Source:  https://web.ornl.gov/sci/techresources/Human_Genome/project/hgp.shtml

History of the Human Genome Project

The Human Genome Project (HGP) refers to the international 13-year effort, formally begun in October 1990 and completed in 2003, to discover all the estimated 20,000-25,000 human genes and make them accessible for further biological study. Another project goal was to determine the complete sequence of the 3 billion DNA subunits (bases in the human genome). As part of the HGP, parallel studies were carried out on selected model organisms such as the bacterium E. coli and the mouse to help develop the technology and interpret human gene function. The DOE Human Genome Program and the NIH National Human Genome Research Institute (NHGRI) together sponsored the U.S. Human Genome Project.

 

Please see the following for goals, timelines, and funding for this project

 

History of the Project

• HGP Goals and Corresponding Completion Dates
• Budget History of the U.S. Human Genome Project
• Timeline: Major Events in the Human Genome Project

It is interesting to note that multiple government legislation is credited for the funding of such a massive project including

Project Enabling Legislation

• The Atomic Energy Act of 1946 (P.L. 79-585) provided the initial charter for a comprehensive program of research and development related to the utilization of fissionable and radioactive materials for medical, biological, and health purposes.
• The Atomic Energy Act of 1954 (P.L. 83-706) further authorized the AEC “to conduct research on the biologic effects of ionizing radiation.”
• The Energy Reorganization Act of 1974 (P.L. 93-438) provided that responsibilities of the Energy Research and Development Administration (ERDA) shall include “engaging in and supporting environmental, biomedical, physical, and safety research related to the development of energy resources and utilization technologies.”
• The Federal Non-nuclear Energy Research and Development Act of 1974 (P.L. 93-577) authorized ERDA to conduct a comprehensive non-nuclear energy research, development, and demonstration program to include the environmental and social consequences of the various technologies.
• The DOE Organization Act of 1977 (P.L. 95-91) mandated the Department “to assure incorporation of national environmental protection goals in the formulation and implementation of energy programs; and to advance the goal of restoring, protecting, and enhancing environmental quality, and assuring public health and safety,” and to conduct “a comprehensive program of research and development on the environmental effects of energy technology and program.”

It should also be emphasized that the project was not JUST funded through NIH but also Department of Energy

Project Sponsors

• The U.S. Department of Energy funded its Human Genome Program through their Office of Biological and Environmental Research. (genome@science.doe.gov).
• The U.S. National Institutes of Health funded its program through the National Human Genome Research Institute (NHGRI).

For a great read on Dr. Craig Ventnor with interviews with the scientist see Dr. Larry Bernstein’s excellent post The Human Genome Project

 

By 2003 we had gained much information about the structure of DNA, genes, exons, introns and allowed us to gain more insights into the diversity of genetic material and the underlying protein coding genes as well as many of the gene-expression regulatory elements.  However there was much uninvestigated material dispersed between genes, the then called “junk DNA” and, up to 2003 not much was known about the function of this ‘junk DNA’.  In addition there were two other problems:

• The reference DNA used was actually from one person (Craig Ventor who was the lead initiator of the project)
• Multiple gaps in the DNA sequence existed, and needed to be filled in

It is important to note that a tremendous amount of diversity of protein has been realized from both transcriptomic and proteomic studies.  Although about 20 to 25,000 coding genes exist the human proteome contains about 600,000 proteoforms (due to alternative splicing, posttranslational modifications etc.)

This expansion of the proteoform via alternate splicing into isoforms, gene duplication to paralogs has been shown to have major effects on, for example, cellular signaling pathways (1)

However just recently it has been reported that the FULL human genome has been sequenced and is complete and verified.  This was the focus of a recent issue in the journal Science.

Source: https://www.science.org/doi/10.1126/science.abj6987

Abstract

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion–base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.

 

The current human reference genome was released by the Genome Reference Consortium (GRC) in 2013 and most recently patched in 2019 (GRCh38.p13) (1). This reference traces its origin to the publicly funded Human Genome Project (2) and has been continually improved over the past two decades. Unlike the competing Celera effort (3) and most modern sequencing projects based on “shotgun” sequence assembly (4), the GRC assembly was constructed from sequenced bacterial artificial chromosomes (BACs) that were ordered and oriented along the human genome by means of radiation hybrid, genetic linkage, and fingerprint maps. However, limitations of BAC cloning led to an underrepresentation of repetitive sequences, and the opportunistic assembly of BACs derived from multiple individuals resulted in a mosaic of haplotypes. As a result, several GRC assembly gaps are unsolvable because of incompatible structural polymorphisms on their flanks, and many other repetitive and polymorphic regions were left unfinished or incorrectly assembled (5).

 

Fig. 1. Summary of the complete T2T-CHM13 human genome assembly.
(A) Ideogram of T2T-CHM13v1.1 assembly features. For each chromosome (chr), the following information is provided from bottom to top: gaps and issues in GRCh38 fixed by CHM13 overlaid with the density of genes exclusive to CHM13 in red; segmental duplications (SDs) (42) and centromeric satellites (CenSat) (30); and CHM13 ancestry predictions (EUR, European; SAS, South Asian; EAS, East Asian; AMR, ad-mixed American). Bottom scale is measured in Mbp. (B and C) Additional (nonsyntenic) bases in the CHM13 assembly relative to GRCh38 per chromosome, with the acrocentrics highlighted in black (B) and by sequence type (C). (Note that the CenSat and SD annotations overlap.) RepMask, RepeatMasker. (D) Total nongap bases in UCSC reference genome releases dating back to September 2000 (hg4) and ending with T2T-CHM13 in 2021. Mt/Y/Ns, mitochondria, chrY, and gaps.

Note in Figure 1D the exponential growth in genetic information.

Also very important is the ability to determine all the paralogs, isoforms, areas of potential epigenetic regulation, gene duplications, and transposable elements that exist within the human genome.

Analyses and resources

A number of companion studies were carried out to characterize the complete sequence of a human genome, including comprehensive analyses of centromeric satellites (30), segmental duplications (42), transcriptional (49) and epigenetic profiles (29), mobile elements (49), and variant calls (25). Up to 99% of the complete CHM13 genome can be confidently mapped with long-read sequencing, opening these regions of the genome to functional and variational analysis (23) (fig. S38 and table S14). We have produced a rich collection of annotations and omics datasets for CHM13—including RNA sequencing (RNA-seq) (30), Iso-seq (21), precision run-on sequencing (PRO-seq) (49), cleavage under targets and release using nuclease (CUT&RUN) (30), and ONT methylation (29) experiments—and have made these datasets available via a centralized University of California, Santa Cruz (UCSC), Assembly Hub genome browser (54).

 

To highlight the utility of these genetic and epigenetic resources mapped to a complete human genome, we provide the example of a segmentally duplicated region of the chromosome 4q subtelomere that is associated with facioscapulohumeral muscular dystrophy (FSHD) (55). This region includes FSHD region gene 1 (FRG1), FSHD region gene 2 (FRG2), and an intervening D4Z4 macrosatellite repeat containing the double homeobox 4 (DUX4) gene that has been implicated in the etiology of FSHD (56). Numerous duplications of this region throughout the genome have complicated past genetic analyses of FSHD.

The T2T-CHM13 assembly reveals 23 paralogs of FRG1 spread across all acrocentric chromosomes as well as chromosomes 9 and 20 (Fig. 5A). This gene appears to have undergone recent amplification in the great apes (57), and approximate locations of FRG1 paralogs were previously identified by FISH (58). However, only nine FRG1 paralogs are found in GRCh38, hampering sequence-based analysis.

Future of the human reference genome

The T2T-CHM13 assembly adds five full chromosome arms and more additional sequence than any genome reference release in the past 20 years (Fig. 1D). This 8% of the genome has not been overlooked because of a lack of importance but rather because of technological limitations. High-accuracy long-read sequencing has finally removed this technological barrier, enabling comprehensive studies of genomic variation across the entire human genome, which we expect to drive future discovery in human genomic health and disease. Such studies will necessarily require a complete and accurate human reference genome.

CHM13 lacks a Y chromosome, and homozygous Y-bearing CHMs are nonviable, so a different sample type will be required to complete this last remaining chromosome. However, given its haploid nature, it should be possible to assemble the Y chromosome from a male sample using the same methods described here and supplement the T2T-CHM13 reference assembly with a Y chromosome as needed.

Extending beyond the human reference genome, large-scale resequencing projects have revealed genomic variation across human populations. Our reanalyses of the 1KGP (25) and SGDP (42) datasets have already shown the advantages of T2T-CHM13, even for short-read analyses. However, these studies give only a glimpse of the extensive structural variation that lies within the most repetitive regions of the genome assembled here. Long-read resequencing studies are now needed to comprehensively survey polymorphic variation and reveal any phenotypic associations within these regions.

Although CHM13 represents a complete human haplotype, it does not capture the full diversity of human genetic variation. To address this bias, the Human Pangenome Reference Consortium (59) has joined with the T2T Consortium to build a collection of high-quality reference haplotypes from a diverse set of samples. Ideally, all genomes could be assembled at the quality achieved here, but automated T2T assembly of diploid genomes presents a difficult challenge that will require continued development. Until this goal is realized, and any human genome can be completely sequenced without error, the T2T-CHM13 assembly represents a more complete, representative, and accurate reference than GRCh38.

 

This paper was the focus of a Time article and their basis for making the lead authors part of their Time 100 people of the year.

From TIME

The Human Genome Is Finally Fully Sequenced

Source: https://time.com/6163452/human-genome-fully-sequenced/

 

The first human genome was mapped in 2001 as part of the Human Genome Project, but researchers knew it was neither complete nor completely accurate. Now, scientists have produced the most completely sequenced human genome to date, filling in gaps and correcting mistakes in the previous version.

The sequence is the most complete reference genome for any mammal so far. The findings from six new papers describing the genome, which were published in Science, should lead to a deeper understanding of human evolution and potentially reveal new targets for addressing a host of diseases.

A more precise human genome

“The Human Genome Project relied on DNA obtained through blood draws; that was the technology at the time,” says Adam Phillippy, head of genome informatics at the National Institutes of Health’s National Human Genome Research Institute (NHGRI) and senior author of one of the new papers. “The techniques at the time introduced errors and gaps that have persisted all of these years. It’s nice now to fill in those gaps and correct those mistakes.”

“We always knew there were parts missing, but I don’t think any of us appreciated how extensive they were, or how interesting,” says Michael Schatz, professor of computer science and biology at Johns Hopkins University and another senior author of the same paper.

The work is the result of the Telomere to Telomere consortium, which is supported by NHGRI and involves genetic and computational biology experts from dozens of institutes around the world. The group focused on filling in the 8% of the human genome that remained a genetic black hole from the first draft sequence. Since then, geneticists have been trying to add those missing portions bit by bit. The latest group of studies identifies about an entire chromosome’s worth of new sequences, representing 200 million more base pairs (the letters making up the genome) and 1,956 new genes.

 

NOTE: In 2001 many scientists postulated there were as much as 100,000 coding human genes however now we understand there are about 20,000 to 25,000 human coding genes.  This does not however take into account the multiple diversity obtained from alternate splicing, gene duplications, SNPs, and chromosomal rearrangements.

Scientists were also able to sequence the long stretches of DNA that contained repeated sequences, which genetic experts originally thought were similar to copying errors and dismissed as so-called “junk DNA”. These repeated sequences, however, may play roles in certain human diseases. “Just because a sequence is repetitive doesn’t mean it’s junk,” says Eichler. He points out that critical genes are embedded in these repeated regions—genes that contribute to machinery that creates proteins, genes that dictate how cells divide and split their DNA evenly into their two daughter cells, and human-specific genes that might distinguish the human species from our closest evolutionary relatives, the primates. In one of the papers, for example, researchers found that primates have different numbers of copies of these repeated regions than humans, and that they appear in different parts of the genome.

“These are some of the most important functions that are essential to live, and for making us human,” says Eichler. “Clearly, if you get rid of these genes, you don’t live. That’s not junk to me.”

Deciphering what these repeated sections mean, if anything, and how the sequences of previously unsequenced regions like the centromeres will translate to new therapies or better understanding of human disease, is just starting, says Deanna Church, a vice president at Inscripta, a genome engineering company who wrote a commentary accompanying the scientific articles. Having the full sequence of a human genome is different from decoding it; she notes that currently, of people with suspected genetic disorders whose genomes are sequenced, about half can be traced to specific changes in their DNA. That means much of what the human genome does still remains a mystery.

The investigators in the Telomere to Telomere Consortium made the Time 100 People of the Year.

Michael Schatz, Karen Miga, Evan Eichler, and Adam Phillippy

Illustration by Brian Lutz for Time (Source Photos: Will Kirk—Johns Hopkins University; Nick Gonzales—UC Santa Cruz; Patrick Kehoe; National Human Genome Research Institute)

BY JENNIFER DOUDNA

MAY 23, 2022 6:08 AM EDT

Ever since the draft of the human genome became available in 2001, there has been a nagging question about the genome’s “dark matter”—the parts of the map that were missed the first time through, and what they contained. Now, thanks to Adam Phillippy, Karen Miga, Evan Eichler, Michael Schatz, and the entire Telomere-to-Telomere Consortium (T2T) of scientists that they led, we can see the full map of the human genomic landscape—and there’s much to explore.

In the scientific community, there wasn’t a consensus that mapping these missing parts was necessary. Some in the field felt there was already plenty to do using the data in hand. In addition, overcoming the technical challenges to getting the missing information wasn’t possible until recently. But the more we learn about the genome, the more we understand that every piece of the puzzle is meaningful.

I admire the

T2T group’s willingness to grapple with the technical demands of this project and their persistence in expanding the genome map into uncharted territory. The complete human genome sequence is an invaluable resource that may provide new insights into the origin of diseases and how we can treat them. It also offers the most complete look yet at the genetic script underlying the very nature of who we are as human beings.

Doudna is a biochemist and winner of the 2020 Nobel Prize in Chemistry

Source: https://time.com/collection/100-most-influential-people-2022/6177818/evan-eichler-karen-miga-adam-phillippy-michael-schatz/

Other articles on the Human Genome Project and Junk DNA in this Open Access Scientific Journal Include:

 

International Award for Human Genome Project

 

Cracking the Genome – Inside the Race to Unlock Human DNA – quotes in newspapers

 

The Human Genome Project

 

Junk DNA and Breast Cancer

 

A Perspective on Personalized Medicine

 

 

 

 

 

 

 

Additional References

 

1. P. Scalia, A. Giordano, C. Martini, S. J. Williams, Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer. Biomolecules 10, (Nov 30, 2020).

 

 

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on LinkedIn (Opens in new window)
• Click to share on Facebook (Opens in new window)
• Click to print (Opens in new window)
• Click to email a link to a friend (Opens in new window)

Like this:

Like Loading...

Read Full Post »

Older Posts »

• Follow Blog via Email

  Enter your email address to follow this blog and receive notifications of new posts by email.

  Email Address

  Follow

  Join 9,329 other subscribers

• Recent Posts

  • The Health Care Dossier on Clarivate PLC: How Cortellis Is Changing the Life Sciences Industry April 16, 2024
  • Live Notes from JP Morgan Healthcare Conference Virtual Endpoints Preview: January 8-9 2024 January 16, 2024
  • The Future of AI in Cardiology November 5, 2023
  • Overview of Alzheimer’s Disease and Novel Treatments Targeting Beta-Amyloid Deposits October 7, 2023
  • The Implications and Association of Stair Climbing with Atherosclerotic Cardiovascular Disease (ASCVD) October 6, 2023
  • The Nobel Prize in Physiology or Medicine 2023 October 2, 2023
  • The Current Impact and Future of Technology within Cardiovascular Surgery September 23, 2023
  • The Continued Impact and Possibilities of AI in Medical and Pharmaceutical Industry Practices September 18, 2023
  • Regulatory T cells (Tregs) are important for sperm tolerance and male fertility September 11, 2023
  • ChatGPT Chemistry Assistant for Text Mining and the Prediction of metal–organic framework (MOF) synthesis August 27, 2023

• Archives

  Archives Select Month April 2024  (1) January 2024  (1) November 2023  (1) October 2023  (3) September 2023  (3) August 2023  (2) July 2023  (2) June 2023  (7) May 2023  (4) April 2023  (2) March 2023  (5) February 2023  (2) January 2023  (3) December 2022  (2) October 2022  (6) September 2022  (2) August 2022  (1) July 2022  (3) June 2022  (3) May 2022  (8) April 2022  (10) March 2022  (7) February 2022  (7) January 2022  (3) December 2021  (3) November 2021  (4) October 2021  (11) September 2021  (5) August 2021  (8) July 2021  (21) June 2021  (8) May 2021  (10) April 2021  (8) March 2021  (15) February 2021  (17) January 2021  (20) December 2020  (10) November 2020  (12) October 2020  (26) September 2020  (17) August 2020  (22) July 2020  (27) June 2020  (33) May 2020  (26) April 2020  (42) March 2020  (22) February 2020  (11) January 2020  (7) December 2019  (20) November 2019  (13) October 2019  (11) September 2019  (3) August 2019  (8) July 2019  (25) June 2019  (47) May 2019  (40) April 2019  (27) March 2019  (29) February 2019  (17) January 2019  (50) December 2018  (14) November 2018  (17) October 2018  (18) September 2018  (17) August 2018  (8) July 2018  (20) June 2018  (22) May 2018  (17) April 2018  (12) March 2018  (20) February 2018  (26) January 2018  (16) December 2017  (6) November 2017  (20) October 2017  (13) September 2017  (16) August 2017  (16) July 2017  (19) June 2017  (20) May 2017  (32) April 2017  (21) March 2017  (10) February 2017  (24) January 2017  (21) December 2016  (43) November 2016  (8) October 2016  (40) September 2016  (67) August 2016  (59) July 2016  (75) June 2016  (37) May 2016  (95) April 2016  (152) March 2016  (175) February 2016  (196) January 2016  (139) December 2015  (90) November 2015  (287) October 2015  (237) September 2015  (115) August 2015  (96) July 2015  (63) June 2015  (44) May 2015  (53) April 2015  (76) March 2015  (95) February 2015  (83) January 2015  (75) December 2014  (75) November 2014  (88) October 2014  (135) September 2014  (117) August 2014  (88) July 2014  (88) June 2014  (109) May 2014  (60) April 2014  (85) March 2014  (58) February 2014  (72) January 2014  (107) December 2013  (104) November 2013  (136) October 2013  (62) September 2013  (32) August 2013  (46) July 2013  (74) June 2013  (110) May 2013  (112) April 2013  (86) March 2013  (92) February 2013  (63) January 2013  (63) December 2012  (46) November 2012  (71) October 2012  (84) September 2012  (82) August 2012  (122) July 2012  (59) June 2012  (34) May 2012  (46) April 2012  (2)

• Categories

  Categories Select Category 3D Printing for Medical Application  (234)    3D Plotting Scaffolds  (43)    BioInks  (33)       Biopolymer Blend Open Porous  (17)       Dental Applications  (10)    BioPrinting in Regenerative Medicine  (74)       Cell Level  (14)       MicroEngineering Cell-Tissue & Systems  (30)       Tissue Engineering  (35)    Cardiovascular and Vascular Systems  (29)       Artificial Vascular Structures  (9)       Cardiovascular Tissue  (8)    Drug Development using MultiOrgan Chip  (11)    Drug Development/Formulation using 3D Printing  (8)    MEMS  (16)       Bio-MEMS  (12)    Organ-on-a-Chip  (11)    Programmable Sensors (Carbon Nano Tubes)  (5) 3rd Party IP: Drug DIscovery  (1) 4D Printing and Meta Materials  (9) Academic Publishing  (222)    Key Opinion Leaders in eScientific Publishing – Interviews with  (8) Advanced Drug Manufacturing Technology  (93)    Antimalarial Preparation  (8)    Autologous Cell Therapy  (12)    Automated Cell Processing  (13) Allergy and Infectious Diseases  (12) Alzheimer’s Disease  (160)    Etiology  (77)    Medical Device Therapies for Altzheimer’s Disease  (14)    Pharmacotherapy and Cell Activity  (50) Anticancer Resistance  (28) Art Exhibits on the Human Condition  (1) Art Inspires Science  (3) Artificial Heart  (2) Artificial Intelligence – General  (194)    An executive’s guide to AI  (9)    Artificial Intelligence – Breakthroughs in Theories and Technologies  (94)    Artificial Intelligence Applications in Health Care  (95)       Artificial Intelligence in CANCER  (28)       Artificial Intelligence in Health Care – Tools & Innovations  (55)    Artificial Intelligence in Medicine – Application for Diagnosis  (52)       Artificial intelligence applications for cardiology  (23)          AI-assisted Cardiac MRI  (9)       Artificial Intelligence in Psychiatry  (5)       Deep Learning in Pathology  (14)    Artificial Intelligence in Medicine – Applications in Therapeutics  (50)    ChatGPT, GPT-4  (4)       ChatGPT at LPBI Group  (2)       ChatGPT in Academic Education  (3)    Machine Learning  (48)       Deep Learning  (8)       Natural Language Processing (NLP)  (25)    Machine learning in predicting type 2 diabetes  (2) Auditory and vision  (13) Autism Spectrum Disorders  (10) Autoimmune Inflammatory DIseases  (21)    Crohn’s disease  (5)    Tolerance-inducing Autoimmune Disease Therapeutics  (4)    Ulcerative Colitis  (3) Autophagosome  (3) Bacterial Resistance  (25) Behavior  (26) Behavioral Genetics  (21) Big Data  (79)    Intelligent Information Systems  (48) Bio Instrumentation in Experimental Life Sciences Research  (365)    Analytical Instruments Industry  (5)    Microfuidics  (8) Bio-Ethics  (14) BioBanking  (33) Biodegradable Drug-eluting Material  (7) Bioengineering & reverse engineering design  (42) BioIT: BioInformatics  (143) BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics  (126)    Advanced Computing Platform  (31)       Blockchain Transactions System  (6)          Platform for Content Monetization embedded Content Promotion  (1)    Pancreatic adenocarcinoma classifier  (4)    Simulation Modeling in NGS  (3) Biological Engineering  (41) Biological Networks  (190) Biological Networks, Gene Regulation and Evolution  (474)    Virology  (10) Biomarkers & Medical Diagnostics  (565)    VOC – Volatile Organic Compounds as BioMarkers  (2) Biomedical Measurement Science  (173) BioSimilars  (111) BioTechnology – Venture Creation  (126)    Foundations for supporting Science and Education  (12)    Philanthropy to Academic Institution  (2) BioTechnology – Venture Creation, Venture Capital  (105)    Seeking Talent  (3) BiVAD  (1) Blindness  (6) Bone Disease and Musculoskeletal Disease  (82) Brain Basis of Emotion  (5) Business Career Consideration  (1) Ca2+ triggered activation  (59) Calcium  (19) Calcium Signaling  (68) Calmodulin Kinase and Contraction  (35) Cancer – General  (177) Cancer and Current Therapeutics  (397)    interventional oncology  (42)       Breast Cancer – impalpable breast lesions  (17)       Prostate Cancer: Monitoring vs Treatment  (8) CANCER BIOLOGY & Innovations in Cancer Therapy  (1,092)    Anaerobic Glycolysis  (51)    Cachexia  (18)    Cancer Genomics  (69)       Circulating Tumor Cells (CTC)  (19)          Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood  (14)             mRNA  (5)          MagSifter chip  (1)       KRAS Mutation  (6)       Li-fraumeni syndrome.  (3)       TP53 – Germline mutations  (5)    cancer metabolism  (20)    Funding Opportunities for Cancer Research  (11)    Genomic Expression  (143)    Glioblastoma  (7)    Hexokinase  (14)    Loss of function gene  (18)    Metabolic Immuno-Oncology  (16)    Metastasis Process  (13)    Methylation  (32)    Microbiome and Responses to Cancer Therapy  (5)    Monoclonal Immunotherapy  (27)    mtDNA  (13)    Oxidative phosphorylation  (56)    Pancreatic cancer  (9)    Pyruvate Kinase  (27)    The NCI Formulary  (1)    tumor microenvironment  (13)    Warburg effect  (50) Cancer Informatics  (93) Cancer Prevention: Research & Programs  (125) Cancer Screening  (102) Cancer Vaccines: Targeting Cancer Genes for Immunotherapy  (25)    Engineering Enhanced Cancer Vaccines  (3) cancer-general  (1) Cardiac and Cardiovascular Surgical Procedures  (321)    Aortic Valve: TAVR, TAVI vs Open Heart Surgery  (87)       Prosthesis-Patient Mismatch (PPM) in TAVI vs SAVR  (2)       TAVI vs Open Heart Surgery  (6)       Transcatheter Aortic Valve Replacement via the Transcarotid Access  (2)       Transcaval TAVR Procedure  (3)       Valve-in-Valve Procedure  (4)    Atrial Fibrilation (a-Fib), Cardiac Pacing and Arrhythmias  (17)    BackBeat’s Cardiac Neuromodulation Therapy (CNT) bioelectronic therapy  (1)    CABG  (47)    Cancer Surgery of the Heart  (10)    Cardiovascular Fluid Management: algorithms  (1)    Heart Transplant  (15)    Heart-Lung Transplant  (10)    Implantation  (2)    Left Main Coronary Artery Disease (LMCAD)  (3)    Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart  (19)    Mitral Valve: Repair and Replacement  (63)       TMVR – Transcatheter Mitral Valve Repair  (4)    PCI  (104)       Bioresorbable Vascular Scaffold (BVS)  (3)       Invasive FFR for PCI  (2)       Multivessel PCI FFR Guidance  (1)       Robotic-assisted percutaneous coronary intervention  (1)       Stent Retriever in endovascular thrombectomy  (2)    Peripheral Arterial Disease & Peripheral Vascular Surgery  (63)       Abdominal Aorta  (20)       Carotid Artery  (15)       Limb ischemia  (4)       Thoracic Aorta  (16)    Pulmonary Valve Replacement and Repair  (3)    Renal Denervation  (20)    Replacement  (1)    Robotically assisted Cardiothoracic Surgery  (1)    Tricuspid Valve Repair  (7)    Vena Caval Filters: Device for Prevention of Pulmonary Embolism and Thrombosis  (1) Cardiovascular Pharmacogenomics  (169) Cargo  (3) Cell Biology  (320) Cell Biology, Signaling & Cell Circuits  (663)    Apoptosis  (17)    Autophagy-Modulating Proteins  (6)    “Antibody–enzyme conjugates”  (5)    Cell Processing System in Cell Therapy Process Development  (25)    Endoplasmic reticulum  (3)    Enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)  (3)    Ubiquitin  (10) Cerebrovascular and Neurodegenerative Diseases  (123)    Stroke  (9) Chemical Biology and its relations to Metabolic Disease  (461)    #BIGAxisSummit  (1)    Gut Microbiome and Obesity  (8) Chemical Genetics  (349) Child and Adolescent Psychiatry  (13) Childhood cancer  (15) Childhood malnutrition  (3) children  (2) Circulating Progenitor Cells  (27)    Bone marrow derived cells  (17)    Endothelial cells  (7)    Umbilical cord cells  (6) Clinical & Translational  (235) Clinical Diagnostics  (216)    Mass automation of plasma proteins  (13) Clinical Genomics  (136) Coagulation Therapy and Internal Bleeding  (83) Cognition  (46) Commercialization  (20) Components and IRB related issues  (4) Computational Biology/Systems and Bioinformatics  (465)    Computational Histopathology  (3)    Meta-analysis of transcriptome data  (9) Conference Coverage with Social Media  (477)    MassBio  (3) coronavirus  (18) COVID-19  (20) CRISPR/Cas9 & Gene Editing  (188)    CRISPR alternative for editing genes without cutting  (14)       CAST – Alternative to CRISPR/Cas9  (3)       Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration  (4)    CRISPR applied to Human Germ Line  (10)       Gene Editing Impact on Longevity  (4) CT  (19) Cytokines  (20) Cytoskeleton  (84) Developmental biology  (107) Diabetes Mellitus  (142)    Artificial Pancreas for Type 2 Diabetes  (1)    Artificial Pancreas for Type1 Diabetes  (5)    Gestational diabetes  (2) Diagnostic Immunology  (58) Diagnostics and Lab Tests  (127)    Liquid Biopsy: Circulating Tumor Cells in Urine and Blood  (8) Digital HealthCare – biotech & internet joint ventures  (46) Disease Biology  (333) Disease Biology, Small Molecules in Development of Therapeutic Drugs  (484) DNA repair  (72)    Apoptosis  (12)    Autophagy  (13)    Cell death pathways  (19)    Proteolysis  (8)    Proteosome  (8) Drug Delivery Platform Technology  (156)    Drug Carrier Design  (20)       Medication Remote Compliance Monitoring  (3)    Exosomes: Natural Carriers for siRNA Delivery  (9) Drug Toxicity  (74) Ecosystems & Industrial Concentration in the Medical Device Sector  (172)    Cardiac & Vascular Repair Tools Subsegment  (128)    Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment  (14)    Massachusetts Niche Suppliers and National Leaders  (20) Electronic Health Record  (9) Embryology  (24) Empathy  (6) Endocrine Diseases  (60) Enzyme Induction  (46)    ion-transporting enzyme  (2)    K + -ATPase.  (1)    Na +  (2) Epigenetics and Environmental Factors  (32) Ethics and Leadership  (10) Executive Compensation – Big Pharma  (3) Fat soluble vitamins  (4) FDA  (68) FDA Regulatory Affairs  (355)    FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP, GLP, ISO 14155  (52)    ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics  (30) Fetal Ultrasound  (2) Fiction and medicine  (5) Frontiers in Cardiology and Cardiovascular Disorders  (920)    Acute Myocardial Infarction  (62)       Cardiogenic Shock  (5)    Anemia in CVD Patients  (6)    Cardio-Oncology  (4)    Cardiomyopathy  (57)    Cardiovascular Research  (187)       Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism  (64)       Pre-Clinical Animal Model Development  (23)    Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH)  (20)    Cost of Inpatient Stay for Cardiovascular Diagnosis for Admission  (1)    Electrophysiology  (108)       Ablation Procedure vs Drug Therapy  (2)       Arrhythmia Detection with Machine Learning Algorithms  (6)       Cardiotoxic Risks of Immune Checkpoint Inhibitors  (1)       Genomic Analysis of EKG Electrophysiology Genomics  (3)       implantable cardioverter defibrillator (ICD) and External Defibrillation  (1)       implantable pacemaker  (2)       Rare heart rhythm disorders and Long QT syndrome (LQTS)  (6)    Epigenetics and Cardiovascular Risks  (57)    Heart Failure (HF)  (48)       Acute coronary syndrome  (6)       congestive heart failure  (18)    Medical Devices R&D and Inventions  (208)       Assist Devices: LV  (3)       RV  (1)       Stents & Tools  (89)       Valves & Tools  (65)    Origins of Cardiovascular Disease  (419)       Atherogenic Processes & Pathology  (178)       Congenital Heart Disease  (34)          Genetic Mutations in Congenital Heart Disease  (4)       inflammation independent of lipid levels  (12)       Systemic Inflammatory Diseases as CVD Risk  (11)    Pharmacotherapy of Cardiovascular Disease  (353)       HTN  (173)       HTN in Youth  (8)       Resident-cell-based  (43)       Subarachnoid Hemorrhage (SAH)  (1)       Transthyretin amyloid cardiomyopathy (ATTR-CM)  (1)    Spontaneous Coronary Artery Dissection (SCAD)  (6)    Stroke  (14)       endovascular thrombectomy  (5)    Vascular Diseases  (21)       mesenteric ischemia  (3) Future Pandemics Inform-graphics  (1) Gastroenterology  (38) Gene Regulation  (228) Gene Regulation and Evolution  (135) Genetics & Innovations in Treatment  (172) Genetics & Pharmaceutical  (199) Genome Biology  (959)    Exosomes  (24)    Gene Therapy & Gene Editing Development  (38)    mRNA Therapeutics  (17)    Mutagenesis  (26)    Single Cell Genomics  (22)    Single-cell sequencing  (18)    Variation in human protein-coding regions  (32) Genomic Endocrinology  (42) Genomic Testing: Methodology for Diagnosis  (412) Genomics Pharmacy  (38) Global Market of Medical Devices Technology  (2) Global Medical Publishers by Country  (3) Global Partnering & Biotech Investment  (45) GLP  (4) Glycobiology: Biopharmaceutical Production  (15) Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics  (27) Health Care System by Country  (49)    AI Models in Healthcare  (8)    Centers for Medicare & Medicaid Services  (8)    Health in Israel  (2)    United States  (24)       Hospital-based Medical Innovations  (8)       Medical Recertification and Maintenance of Certification (MOC)  (1) Health Economics and Outcomes Research  (378)    Women Health  (15)       Heart and Brain Disease in Women  (3) Health Law & Patient Safety  (162)    and Bioethics  (13)    Biotechnology  (11)    Health Law Policy  (12) HealthCare IT  (136) Healthcare Reform  (112)    Accountable Care Organizations  (26)    Affordable Care Act  (29)       Repair  (1)       Repeal ACA  (1)       Replace  (1)    Federal Budget Appropriations  (26)    Healthcare costs and reimbursement  (55)    Indigent Nutrition  (14)    Medicare and Medicaid  (20)    Prescription Drugs Costs  (21)    Skilled Nursing Facilities  (6)    Technology Capital Expenses  (15)    Uninsured and Underinsured  (20) Hematology  (99)    Acute lymphocytic leukemia  (18)    Acute myelocytic leukemia  (21)    Hematopoiesis  (48)    Lymphoma  (21) History and physical exam  (6) Human aging  (27) Human Immune System in Health and in Disease  (237) Human Sensation and Cellular Transduction: Physiology and Therapeutics  (21) Image Processing/Computing  (41) Imaging-based Cancer Patient Management  (116) Immuno-Oncology & Genomics  (126)    mRNA platform in Drug DIscovery  (6) Immunodiagnostics  (128)    Cancer-Immune Interactions  (20)    CNS-Immune Interface  (3)    Neuronal Circuits  (4) Immunology  (114)    Adaptive Immune Response to Biomaterials and Tissue Repair  (10)    Antibody Responses Predict Antigen Exposure  (15)    Cytokine Receptor Structure  (8)    Human Antibody Response  (17)    Human Circulating Antibody Repertoire  (10)    Human Naive B Cell Repertoire  (8)    MHC Repertoires for Antigen Prediction  (8)    Protection Against Autoimmune Disease  (9)    Synthetic Immunology: Hacking Immune Cells  (12) Immunotherapy  (121)    CAR-T  (13)    combination immunotherapies.  (11)    Efficacy of Anti-Tumor T Cells  (11)    Engineering Better T Cells  (7)    Immune Engineering  (13)    Immune Modulatory  (13)    Integrin-targeted Combination Immunotherapy  (5)    Modulating Macrophages in Cancer Immunotherapy  (11)    NK Cell-Based Cancer Immunotherapy  (16)    Synergistic Innate and Adaptive Immunotherapy  (13) Income Disparity  (2) Infectious Disease & New Antibiotic Targets  (162)    Antibiotic resistance  (7)    Viral diseases  (37)       Myocarditis  (1) Infectious Disease Immunodiagnostics  (56)    Virology – Vector-borne DIsease  (17) Inflammasome  (26)    Anti-tumor necrosis factor drugs (TNF inhibitors)  (2) Innovation in Immunology Diagnostics  (107)    Universal Immune Cell Therapies (uICT)  (10) Innovations  (185)    R&D Expenditure  (8) Innovations in Neurophysiology & Neuropsychology  (142)    Age and Life Expectancy  (1)    autism spectrum disorder  (1)    Circadian Rhythm and Sleep  (6)    hNPCs  (1)    Nervous System Function  (2)    Relapsing Multiple Sclerosis  (1) Intellectual Property  (76)    Disputes and Settlements  (9)    IP Valuation Models – Pricing Intangible Assets  (5)    Patent Law in Biotech  (12) Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough  (108) International Global Work in Pharmaceutical  (188) Interventional Oncology: Radiofrequency Ablation, Transarterial Chemoembolization, Microwave Ablation and Irreversible Electroporation (IRE)  (12) Interviews with Scientific Leaders  (302)    Albany Medical Center Prize in Medicine and Biomedical Research  (1)    Annual Breakthrough Prize  (2)    Annual Lewis S. Rosenstiel Award  (1)    Awards in Cardiology and Cardiovascular Medicine  (4)    CEOs of Biotech Companies  (2)    Gerald D Aurbach Award for Outstanding Translational Research  (1)    Interviews with Key Opinion Leaders (KOLs)  (7)    James Prize in Science and Technology Integration  (1)    Jessie Stevenson Kovalenko Medal – Medical Sciences  (1)    Lemelson-MIT Prize  (1)    Life Sciences Breakthrough Prize  (3)    Mosteller Statistician of the Year Award  (1)    Mourning the Loss of a Scientific Leader  (2)    National Academy of Sciences AWARDS  (2)    Nobel Prize Winners  (21)    Noble Prize (Not Nobel Prize)  (1)    Paul Marks Prize for Cancer Research  (1)    Russ Prize recognizes bioengineering achievements worldwide  (1)    The Dan David Prize  (5)    Warren Alpert Foundation Prize Recipients  (3)    Wolf Prize  (1)    Wolf Prize in Medicine  (1)    women in science  (3) Investment in Technological Breakthrough  (60) Ionic Transporters Na+  (25) IP Development by LPBI Group Team  (10) IP Development by LPBI Group Team & Other Organizations  (7) ISO 14155  (3) Joint Venture – SBH & M3DP: SOP and Arrangements  (1) Justice & Law  (1) K  (15) Lab-on-a-chip  (2) Landscape  (1) Lasers and photonics  (18)    Midrange IR spectroscopy  (1) Law and Medicine Conflicts  (14) Leadership, Power, Social Interlocking Connections  (13) Lipid metabolism  (109)    Fatty acids  (38)    Lipids  (38)    PCSK9 Inhibitor Therapy  (19) Lipidomics  (11) Liposome  (4) Liver & Digestive Diseases Research  (120) LPBI Group, e-Scientific Media, DFP, R&D-M3DP, R&D-Drug Discovery, US Patents: SOPs and Team Management  (129)    Award Nominations  (5)    BioMed e-Books e-Series by LPBI Group  (8)    Feedback from Investors: LPBI Portfolio of Five Businesses  (2)    LPBI Group Founder – Aviva Lev-Ari  (22)    PhD  (1)    RN  (1) LPBI Management  (15) Massachusetts Academy of Sciences (MAS)    (2) Materials Science & Engineering  (37)    Organic BioElectronics  (2) Math  (13)    Great Discoveries  (7) Mechanical Assist Devices: LVAD  (4) Medical and Population Genetics  (191) Medical Devices R&D Investment  (239)    21st Century Cures Act  (2)    CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP  (13)    Rhythm management device hardware: dual-chamber pacemakers  (1)       Systolic HTN  (1) Medical Imaging Technology  (55) Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound  (160)    Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI)  (3)    Echocardiography  (2)    MRI  (17)    Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT  (5)    Ultra Sound  (7) Melatonin & Circadian Regulation  (9) memory loss  (1) Metabolism  (236)    Biochemical pathways  (142)       Enzymes and isoenzymes  (72)          Dehydrogenase  (16)          Kinase  (28)          Phosphatase  (9)          Phosphorylase  (22)          tyrosine decarboxylases  (3)    Inosine nucleotides  (9)    Leloir pathway  (6)    microbiome  (7)    Pentose monophosphate shunt  (14)    Pyridine nucleotides  (28)       Pyridine nucleotide transhydrogenase  (7) Metabolomics  (318) Methods  (37) Mg++  (10) Microbiologial genetics  (34) Microbiology  (67)    Virology  (14) Micronutrients  (16) Microvesicle  (7) Microwave Ablation and Irreversible Electroporation (IRE)  (1) Mobile Healthcare  (4) Molecular Genetics & Pharmaceutical  (375)    Organoids  (3) Monoclonal antibody therapy  (13) Mutant Gene Expression  (42) Myocardial adenine nucleotide metabolism  (6) Myocardial Ischemia  (26) Myocardial Metabolism  (36) Na-K transport  (40) Na-K-ATPase  (27) Nanotechnology for Drug Delivery  (97) Nephrology  (46) Nephrology & Regenerative medicine  (9) Neurodegenerative Diseases  (88)    hNPCs  (3)    MS  (5) Neurohumoral Transmission  (67)    Ca2+ triggered activation  (20)    Calmodulin  (13)    Parkinson’s disease dyskinesia levodopa  (3)    PKC  (13)    Synaptic vesicle  (20) Neurological Diseases  (121) Neuroscience  (126) Next Generation Sequencing (NGS)  (25)    Nanopore sequencing  (1) NIH Common Fund  (1) Nitric Oxide in Health and Disease  (136) Nuclear Medicine  (11) Nutrigenomics  (68) Nutrition  (194)    Nutritional Supplements: Atherogenesis, lipid metabolism  (49) Nutrition and Phytochemistry  (61)    Minerals in Medicine  (4)    Plant extract  (22) Nutrition Disorders  (30) Nutritional Supplements: Atherogenesis  (31) Obesity  (18) Oligonucleotide Therapeutics & Delivery  (7) Oncolytic virus & OncoViro-Therapy  (21)    Synthetic Virology  (1) Organ-on-a-Chip & 3D Printing in Life Sciences  (7) Pain: Etiology, Genetics & Innovations in Treatment  (24) Parasitology  (5)    Malaria  (4)    Tropical diseases  (1) Patents  (34) Patient Experience  (64)    Art therapy  (1)    Hospital reputation  (7)    Humor  (1)    Music therapy  (2)    Pain Alleviation  (7)    Patient Outlook  (28)    Reputation of Interventionist  (4)    Support Staff  (13)    Supportive therapies  (6)       laughfter  (1)    Surgical Procedure  (7) Patient Experience: Personal Memories of Invasive Medical Intervantion  (30) Patient’s Voice: Personal Experience with Invasive Medical Procedures  (18) Perioperative Statins at Noncardiac Surgery  (2) Personal Health Applications: Tech Innovations serves HealhCare  (36) Personalized and Precision Medicine & Genomic Research  (717)    Longevity  (2)    New Drug Approval  (5)    Patient-centered Medicine  (35)       cell-based therapy  (8)       stem cell biology and patient-specific  (6)    Personalized Medicine Coalition  (8)    Precision Cancer Medicine  (18) Phagophore  (2) Pharmaceutical Analytics  (259)    Pharmacologic toxicities  (61) Pharmaceutical Discovery  (107)    Rapid automation of plasma protein pools  (16) Pharmaceutical Drug Discovery  (198)    Drug Development Process  (55)       Drug Discovery Chemistry  (29)    drug repurposing  (10) Pharmaceutical Industry Competitive Intelligence  (339)    Pharmacovigilance  (6)    Value-based Drug Pricing  (8) Pharmaceutical R&D Informatics  (43) Pharmaceutical R&D Investment  (297) Pharmacodynamics and Pharmacokinetics  (24) Pharmacogenomics  (157) Photography Collection  (1) Physics  (12) Placenta  (7) Population genetics  (25) Population Health Management  (192)    Evolution of Biology Through Culture  (14)    U.S. Employment-to-Population Ratio  (8) Population Health Management, Genetics & Pharmaceutical  (623)    COVID-19  (155)       Biomarkers: Inflammation  (36)       Cancer Researchers Fighting COVID-19  (14)       COVID-19 effects on Human Heart  (15)       COVID-19: Pandemic Surgery Guidance  (19)       Economic Impact of Coronavirus Pandemic  (41)       number of asymptomatic infections  (27)       Treatment Protocols for COVID-19  (62)    SARS-CoV-2  (138)       Coronavirus Gene Expression  (65)          SARS-CoV-2 circulating variants   (14)          SARS-CoV-2 Viral Variants  (18)       Glycosylation and its Role in SARS-CoV-2 Viral Pathogenesis  (2)       Immune-Mediation (independent immunopathology: lung and reticuloendothelial system)  (29)       Mechanisms of infection by SARS-CoV-2  (21)       SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus  (35)          SARS-COV2 Hijacking the Complement and Coagulation Systems  (19)       Seasonality & Environmental Factors in Resurgence  (26)       Serology tests for coronavirus antibodies  (44)       T-cell response to SARS-CoV-2 infection  (14)       Vaccinology  (51)          Mechanism of Thrombosis with AZ & J&J COVID-19 Vaccines  (5)       Virtual Drug Molecule Screening targeting SAR-CoV-2 proteins  (8)    Virus Infective Acute Respiratory Syndrome: SARS-CoV  (92) Population Health Management, Nutrition and Phytochemistry  (151) Preimplantation Genetic Diagnosis and Reproductive Genomics  (13) Protein-energy malnutrition  (12) Proteomics  (360)    Amino acids  (52)    Proteins  (134) Pulmonary diseases  (16)    Lung and pulmonology  (15) Pulmonary pathology  (8) Radio Frequency (RF)-based Surgical Solutions  (2) REAL TIME Conference Coverage Twitter’s Hashtags and Handles per Presentation/session  (31) Regenerative Biology and Medicine  (92) Regulated Clinical Trials: Design, Methods, Components and IRB related issues  (265) Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics  (113) Reproductive Biology & Bio Instrumentation  (78) RNA Biology  (81)    RNA interference (RNAi) therapeutic  (4) RNA Biology, Cancer and Therapeutics  (62) RVAD  (1) SBIR, SBA, NIH, NSF  (3) Schizophrenia  (16) Scientific & Biotech Conferences: Press Coverage  (174) Scientific Publishing  (607)    Curation  (584)       Curation methodology  (40)       De novo synthesis  (16)       Dialectic  (17)       Discovery process  (71)       Evolutionary cognition  (52)       Experimental validation  (90)       Explanatory  (91)       Historical relevance  (71)       Technology Advance Assessment of  (69)       Theoretic convergence  (27)    Open Access Journals  (37) Scientist: Career considerations  (196)    Big Data & Analytics  (17)    Data Science  (13)    Women in Life Sciences  (11) Scoop.it  (19) Sensors & Analytics  (18) Sepsis  (2) Severe Autism  (3) Signaling  (100)    Phosphorylation  (42)    S-nitrosylation  (13)    Ubiquitinylation  (33) Signaling & Cell Circuits  (129) single cell sequencing  (2) Small Molecules in Development of Therapeutic Drugs  (70) Social Development  (15) Specialized 3D BioPrinters (Cornea  (1) Statistical Methods for Research Evaluation  (137) Stem Cells for Regenerative Medicine  (175)    Cardiac muscle regeneration  (19)    Competition in regenerative stem cell science  (17)    Human neural progenitor cells  (7)    Skeletal muscle regeneration  (9) STORM  (2) Stress Disorders  (19) Substance Abuse  (4) Systemic Inflammatory Response Related Disorders  (160)    Inflammatory Pathophysiology  (8) Technology Transfer: Biotech and Pharmaceutical  (353) therapeutics  (3) Tissue Engineering and Regenerative Medicine  (22) Tissue Microenvironment  (4) Transarterial Chemoembolization  (2) Transcriptomics  (43) Transformative Technologies in Healthcare  (14) Translational Science  (226)    Best evidence  (52)    Bias measurement tools  (2)    Evidence-based decision-making  (27)    Inferential analysis  (25)    Intra-rater error  (1)    Quality Assurance  (8)    Random Error  (2)    Systematic Error (Bias)  (6)    Total error  (2)    Translational Effectiveness  (49)    Translational Research  (89) Trends in Global Economy  (6) Uncategorized  (1,009) Unfolded Protein Response (UPR)  (6) US and Global Economy: Trends and Findings  (9) Venture Capital  (45)    Income Geographic Distribution  (2)    Institutional Capital Raised by Female Founders  (6) virology  (9) Vision  (7) Voices of Patients and Healthcare Providers  (21) Water Transporters  (8) Wearable Tech + Digital Health  (4) Anemia  (21) Neutropenia  (8) Neutrophilia  (9) Platelet count disorder  (9) Folate and B12  (7) Iron deficiency  (5) Myelodysplasia  (12) Myelofibrosis  (10)

• Meta

  • Log in
  • Entries feed
  • Comments feed
  • WordPress.org

• • 2012pharmaceutical
  • Amandeep Kaur
  • Aashir Awan, Phd
  • Abhisar Anand
  • Adina Hazan
  • Alan F. Kaul, PharmD., MS, MBA, FCCP
  • alexcrystal6
  • anamikasarkar
  • apreconasia
  • aptubman
  • Arav Gandhi
  • aviralvatsa
  • David Orchard-Webb, PhD
  • danutdaagmailcom
  • Demet Sag, Ph.D., CRA, GCP
  • Dror Nir
  • dsmolyar
  • Ethan Coomber
  • evelinacohn
  • Gail S Thornton
  • Irina Robu
  • jayzmit48
  • jdpmd
  • jshertok
  • kellyperlman
  • Ed Kislauskis
  • larryhbern
  • Madison Davis
  • marzankhan
  • megbaker58
  • ofermar2020
  • Dr. Pati
  • pkandala
  • ritusaxena
  • Rick Mandahl
  • sjwilliamspa
  • Srinivas Sriram
  • stuartlpbi
  • Dr. Sudipta Saha
  • tildabarliya
  • zraviv06
  • zs22