terrific in every respect
terrific in every respect
Posted in Uncategorized | Leave a Comment »
Biochemical Insights of Dr. Jose Eduardo de Salles Roselino
Larry H. Bernstein, MD, FCAP, Interviewer, Curator
Leaders in Pharmaceutical Intelligence
Biochemical Insights of Dr. Jose Eduardo de Salles Roselino
http://pharmaceuticalintelligence.com/12/24/2014/larryhbern/Biochemical_
Insights_of_Dr._Jose_Eduardo_de_Salles_Roselino/
Article ID #165: Biochemical Insights of Dr. Jose Eduardo de Salles Roselino. Published on 12/17/2014
WordCloud Image Produced by Adam Tubman
Biochemical Insights of Dr. Jose Eduardo de Salles Roselino
How is it that developments late in the 20th century diverted the attention of
biological processes from a dynamic construct involving interacting chemical
reactions under rapidly changing external conditions effecting tissues and cell
function to a rigid construct that is determined unilaterally by the genome
construct, diverting attention from mechanisms essential for seeing the complete
cellular construct?
Larry, I assume that in case you read the article titled Neo – Darwinism, The
Modern Synthesis and Selfish Genes that bares no relationship with Physiology
with Molecular Biology J. Physiol 2011; 589(5): 1007-11 by Denis Noble, you might
find that it was the key factor required in order to understand the dislodgment
of physiology as a foundation of medical reasoning. In the near unilateral emphasis
of genomic activity as a determinant of cellular activity all of the required general
support for the understanding of my reasoning. The DNA to protein link goes
from triplet sequence to amino acid sequence. That is the realm of genetics.
Further, protein conformation, activity and function requires that environmental
and micro-environmental factors should be considered (Biochemistry). If that
were not the case, we have no way to bridge the gap between the genetic
code and the evolution of cells, tissues, organs, and organisms.
- Consider this example of hormonal function. I would like to stress in
the cAMP dependent hormonal response, the transfer of information
that occurs through conformation changes after protein interactions.
This mechanism therefore, requires that proteins must not have their
conformation determined by sequence alone.
Regulatory protein conformation is determined by its sequence plus
the interaction it has in its micro-environment. For instance, if your
scheme takes into account what happens inside the membrane and
that occurs before cAMP, then production is increased by hormone
action. A dynamic scheme will show an effect initially, over hormone
receptor (hormone binding causing change in its conformation) followed
by GTPase change in conformation caused by receptor interaction and
finally, Adenylate cyclase change in conformation and in activity after
GTPase protein binding in a complex system that is dependent on self-
assembly and also, on changes in their conformation in response to
hormonal signals (see R. A Kahn and A. G Gilman 1984 J. Biol. Chem.
v. 259,n 10 pp6235-6240. In this case, trimeric or dimeric G does not
matter). Furthermore, after the step of cAMP increased production we
also can see changes in protein conformation. The effect of increased
cAMP levels over (inhibitor protein and protein kinase protein complex)
also is an effect upon protein conformation. Increased cAMP levels led
to the separation of inhibitor protein (R ) from cAMP dependent protein
kinase (C ) causing removal of the inhibitor R and the increase in C activity.
R stands for regulatory subunit and C for catalytic subunit of the protein
complex. - This cAMP effect over the quaternary structure of the enzyme complex
(C protein kinase + R the inhibitor) may be better understood as an
environmental information producing an effect in opposition to
what may be considered as a tendency towards a conformation
“determined” by the genetic code. This “ideal” conformation
“determined” by the genome would be only seen in crystalline
protein. In carbohydrate metabolism in the liver the hormonal signal
causes a biochemical regulatory response that preserves homeostatic
levels of glucose (one function) and in the muscle, it is a biochemical
regulatory response that preserves intracellular levels of ATP (another
function). - Therefore, sequence alone does not explain conformation, activity
and function of regulatory proteins. If this important regulatory
mechanism was not ignored, the work of S. Prusiner (Prion diseases
and the BSE crisis Stanley B. Prusiner 1997 Science; 278: 245 – 251,
10 October) would be easily understood. We would be accustomed
to reason about changes in protein conformation caused by protein
interaction with other proteins, lipids, small molecules and even ions. - In case this wrong biochemical reasoning is used in microorganisms.
Still it is wrong but, it will cause a minor error most of the time, since
we may reduce almost all activity of microorganism´s proteins to a
single function – The production of another microorganism. However,
even microorganisms respond differently to their micro-environment
despite a single genome (See M. Rouxii dimorphic fungus works,
later). The reason for the reasoning error is, proteins are proteins
and DNA are DNA quite different in chemical terms. Proteins must
change their conformation to allow for fast regulatory responses and
DNA must preserve its sequence to allow for genetic inheritance.
Posted in Biochemical pathways, Ca2+ triggered activation, Chemical Biology and its relations to Metabolic Disease, Computational Biology/Systems and Bioinformatics, Curation, Developmental biology, Dialectic, Disease Biology, Endocrine Diseases, Enzyme Induction, Enzymes and isoenzymes, Evolutionary cognition, Experimental validation, Explanatory, Gene Regulation and Evolution, Hematopoiesis, Historical relevance, Human Immune System in Health and in Disease, Interviews with Scientific Leaders, Lipid metabolism, Metabolism, Metabolomics, Na-K transport, Nephrology, Neurodegenerative Diseases, Neurohumoral Transmission, Neurological Diseases, Nitric Oxide in Health and Disease, Synaptic vesicle | Tagged cell surface interactions, cell-cell interactions, Cytoskeleton, cytoskeleton transport, epigenetic pathways, intercellular bridging, intracellular flux, intracellular localization, ion channels, Metabolism, protein conformation, protein modifications, protein-protein interaction networks, Proteins, quaternary structure, structural constraints, synaptic function | Leave a Comment »
Reprogramming Normal Cell Lines into Stem-like Cells
Reporter: Aviva Lev-Ari, PhD, RN
More information: “Actin stress in cell reprogramming.” PNAS 2014 111 (49) E5252-E5261; published ahead of print November 24, 2014, DOI: 10.1073/pnas.1411683111
Read more at: http://phys.org/news/2014-12-mechanical-cues-reprogram-cell-lines.html#jCp
and
http://phys.org/news/2014-12-mechanical-cues-reprogram-cell-lines.html
Mechanical cues reprogram normal cell lines into stem-like cells
Dec 11, 2014 by Ellen Goldbaum
Scientists at the University at Buffalo and other institutions have turned cells normally used as model cells, known as immortalized cells, into stem or, as they call it, “stem-like” cells, using nothing more than mechanical stress. They have done it without employing the potentially hazardous techniques previously used to obtain similar results.
The finding is described in a paper published recently online before print in the Proceedings of the National Academy of Sciences. The researchers discovered that by changing the mechanical stresses on neuronal and other cell types in tissue culture allowed them to be reprogrammed into “stem-like” cells.
“Normal cell types in tissue culture are spread out and have differentiated internal structures, but changing cell mechanics caused the cells to turn into clusters of spherical cells that had many of the biochemical markers of cells,” says Frederick Sachs, PhD, SUNY Distinguished Professor in the UB Department of Physiology and Biophysics and senior author.
Read more at: http://phys.org/news/2014-12-mechanical-cues-reprogram-cell-lines.html#jCp
Posted in Stem Cells for Regenerative Medicine | Leave a Comment »
Biologically Distinct Breast Cancer Subtypes: The Role of Epigenetics
Reporter: Aviva Lev-Ari, PhD, RN
Article reference
A DNA methylation-based definition of biologically distinct breast cancer subtypes. Stefansson OA, Moran S, Gomez A, Sayols S, Arribas-Jorba C, Sandoval J, Hilmarsdottir H, Ólafsdóttir I, Tryggvadottir L, Jonasson JG, Eyfjord J, Esteller M. Molecular Oncology, PII: S1574-7891 (14) 00261 -0, 2014.
Mol Oncol. 2014 Nov 5. pii: S1574-7891(14)00261-0. doi: 10.1016/j.molonc.2014.10.012. [Epub ahead of print]
A DNA methylation-based definition of biologically distinct breast cancer subtypes.
Stefansson OA1, Moran S1, Gomez A1, Sayols S1, Arribas-Jorba C1, Sandoval J1, Hilmarsdottir H2, Olafsdottir E3, Tryggvadottir L3, Jonasson JG4,Eyfjord J2, Esteller M5.
Abstract
In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays. The identified methylation signatures were validated against a cohort of 212 tumors annotated for breast cancer subtypes by the PAM50 method (The Cancer Genome Atlas). Selected markers were pyrosequenced in an independent validation cohort of 310 tumors and analyzed with respect to survival, clinical stage and grade. The results demonstrate that DNA methylation patterns linked to the luminal-B subtype are characterized by CpG island promoter methylation events. In contrast, a large fraction of basal-like tumors are characterized by hypomethylation events occurring within the gene body. Based on these hallmark signatures, we defined two DNA methylation-based subtypes, Epi-LumB and Epi-Basal, and show that they are associated with unfavorable clinical parameters and reduced survival. Our data show that distinct mechanisms leading to changes in CpG methylation states are operative in different breast cancer subtypes. Importantly, we show that a few selected proxy markers can be used to detect the distinct DNA methylation-based subtypes thereby providing valuable information on disease prognosis.
NEW BREAST CANCER CLASSIFICATION BASED ON EPIGENETICS.
Statistics from The Breast Cancer Research Foundation state that nearly 1.7 million new breast cancer cases were diagnosed in 2012. Breast cancer is the second most common cancer in women and men worldwide. In 2012, it represented about 12 percent of all new cancer cases and 25 percent of all cancers in women. Breast cancer is the most frequently diagnosed cancer among women in 140 of 184 countries worldwide.
Globally, breast cancer now represents one in four of all cancers in women. Progress in prevention and early detection, and the use of chemotherapy after surgery (adjuvant chemotherapy), have achieved significantly increase survival in this disease in the last ten years, but much remains to be done.
The identification of patients with high-risk breast cancer is key to knowing whether a patient will require only the removal of the tumour by surgery or whether if they will need additional chemotherapy to make sure the removal of breast cancer cells. Currently, known genetic mutations and expression patterns are determined, but the puzzle of the genetics of the disease remains a large unfinished part.
To address this the researchers analyzed epigenetic alterations, namely the chemical signal called DNA methylation in 500 breast tumours and have compared the patterns obtained with the clinical behaviour of these cancers.
The team note that there are two subgroups of breast tumours by epigenome; one which they have named Epi-Basal, characterized by loss of epigenetic marks causing breakage of chromosomes and the other that the researchers have called Epi-Luminal B, that presents epigenetic inactivation of genes that should protect humans from cancer and the altered cells that can no longer do it.
The researchers highlight that the subtype Epi-Luminal B behaves particularly aggressive form, and is associated with reduced survival of patients. They would therefore recommend that with this class of tumour the medical team avoid surgery and instead administer adjuvant chemotherapy and in those tumours with a more ‘benign’ epigenetic pattern; surgery alone may be curative, thus avoiding the side effects of chemotherapy.
Source: Institut d’Investigació Biomèdica de Bellvitge
Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Genomic Expression | Leave a Comment »
Dynamic myocardial CT perfusion imaging for evaluation of myocardial ischemia as determined by MR imaging | DSCT.com – Your Dual-source CT experts
Reporter: Aviva Lev-Ari, PhD, RN
The aim of this study was to determine the feasibility of CT-based dynamic myocardial perfusion imaging for the assessment of myocardial ischemia and infarction compared with cardiac magnetic resonance (CMR).
Source: www.dsct.com
Posted in Frontiers in Cardiology and Cardiovascular Disorders, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, MRI, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT | Leave a Comment »
Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis – Online First – Springer
Reporter: Aviva Lev-Ari, PhD, RN
Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: … http://t.co/752c9CuBzz
Source: link.springer.com
Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, cancer metabolism, Metastasis Process | Leave a Comment »
“@smithECGBlog: A Hybrid of de Winter’s T-waves and Diffuse Subendocardial Ischemia: #FOAMed http://t.co/IBTUwRX5KE http://t.co/LSFDBp1ipa”
Source: hqmeded-ecg.blogspot.fr
Posted in Uncategorized | Leave a Comment »
Myocardial ischemia common in young women with CHD under mental stress | Cardiology
Reporter: Aviva Lev-Ari, PhD, RN
Cardiology | CHICAGO — Women aged 55 years and younger with stable CHD under mental stress are more likely to develop myocardial ischemia than men of the same age.
Source: www.healio.com
Posted in Frontiers in Cardiology and Cardiovascular Disorders, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism | Leave a Comment »
Follow Blog via Email
Join 2,056 other subscribers-
Recent Posts
- Grok thinks like PhDs – Hybrid Model for Autonomous Update of Doctoral Dissertations with Original PhD Student Author editing and acceptance of Grok’s updated output. 3rd Joint article, a pilot study for Validation of an Autonomous Journal Articles Updating System (AJAUS) tested on Autonomous Update of Aviva Lev-Ari, PhD, RN Doctoral Thesis, UC, Berkeley, 1983. January 31, 2026
- 2026 World Economic Forum, 1/19 – 1/23/2026, Davos, Switzerland, LPBI Group’s KOLs interpretation of AI in Health Videos January 24, 2026
- Evolving LPBI Group’s Portfolio of Intellectual Properties (IP): From 2021 Vision to 2026 Reality January 12, 2026
- Aviva Lev-Ari, PhD, RN – Biography ->> Grokepedia Entry January 11, 2026
- List of Articles included in the Article SELECTION from Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com for Training Small Language Models (SLMs) in Domain-aware Content of Medical, Pharmaceutical, Life Sciences and Healthcare by 15 Subjects Matter January 10, 2026
- Article SELECTION from Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com for Training Small Language Models (SLMs) in Domain-aware Content of Medical, Pharmaceutical, Life Sciences and Healthcare by 15 Subjects Matter January 10, 2026
- Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com January 10, 2026
- The youngest leader in AI in Health: Tanishq Mathew Abraham, Ph.D. (@iScienceLuvr) January 8, 2026
- 2026 Grok Multimodal Causal Reasoning on Proprietary Cariovascular Corpus: From 2021 Wolfram NLP Baseline to Thousands of Novel Relationships – A Second Head-to-Head Validation of LPBI’s Domain-Aware Training Advantage January 6, 2026
- Workflow for Dynamic Linkage and Transition between two Authoring Systems: LPBI Group’s WordPress.com Multi-Authors Authoring System and Microsoft PowerPoint product for Slide show presentation – Part 10.1 in Composition of Methods January 6, 2026
Archives
Categories
Meta
2012pharmaceutical
sjwilliamspa