This document discusses microRNAs (miRNAs), which are small non-coding RNAs that regulate gene expression. It describes several strategies to inhibit oncogenic miRNAs that are overexpressed in tumors, including anti-miRNA oligonucleotides, miRNA antagomirs, and miRNA sponges. Lentiviral vectors derived from HIV-1 can be used to deliver short hairpin RNAs, miRNAs, or genes into cells. Several tumor suppressor miRNAs (miR-145, miR-34a, miR-29b, Let-7a, miR-340, miR495) and oncogenic miRNAs (miR155, miR-21) are described along with their gene targets and the results of in
microRNA for Clinical Research and Tumor AnalysisBioGenex
The discovery of microRNAs [miRNAs] has been one of the defining developments in cancer biology over the past decade. miRNAs are short, single stranded 20-22 nucleotide long, non-coding RNAs that regulate gene expression and have fundamental roles in Cancer growth and metastasis. miRNAs exert their function via base pairing with complementary mRNA molecules, resulting in gene silencing via transcriptional repression or target degradation. BioGenex solved the inherent difficulties in visualizing miRNAs in spatial context by using a propriety technology to synthesize modified, high-affinity oligonucleotides, labelling miRNA probes with multiple reporter molecules and developing a fully-integrated miRNA-ISH workflow solution allowing high throughput analysis of miRNA in the spatial context.
DNA and RNA Structure
Central Dogma of Life
Protein Engineering (Brief)
Introduction to microRNA (miRNA)
History of miRNA
Biogenesis of miRNA
Conservation of miRNA
Impact of miRNA
miRNA Therapy
Conclusion
Scientists have recently explored the amazing discovery that many cells produce thousands of much smaller RNA molecules, micro RNAs. Instance, more than 500 different micro RNAs have been found in human cells alone.
Micro RNA plays an important role in post-transcriptional gene regulation, such as RISC, and can cause interference and shut down gene activity.
Micro RNA is a form of ribonucleic acid and does not contain genetic information.
microRNA for Clinical Research and Tumor AnalysisBioGenex
The discovery of microRNAs [miRNAs] has been one of the defining developments in cancer biology over the past decade. miRNAs are short, single stranded 20-22 nucleotide long, non-coding RNAs that regulate gene expression and have fundamental roles in Cancer growth and metastasis. miRNAs exert their function via base pairing with complementary mRNA molecules, resulting in gene silencing via transcriptional repression or target degradation. BioGenex solved the inherent difficulties in visualizing miRNAs in spatial context by using a propriety technology to synthesize modified, high-affinity oligonucleotides, labelling miRNA probes with multiple reporter molecules and developing a fully-integrated miRNA-ISH workflow solution allowing high throughput analysis of miRNA in the spatial context.
DNA and RNA Structure
Central Dogma of Life
Protein Engineering (Brief)
Introduction to microRNA (miRNA)
History of miRNA
Biogenesis of miRNA
Conservation of miRNA
Impact of miRNA
miRNA Therapy
Conclusion
Scientists have recently explored the amazing discovery that many cells produce thousands of much smaller RNA molecules, micro RNAs. Instance, more than 500 different micro RNAs have been found in human cells alone.
Micro RNA plays an important role in post-transcriptional gene regulation, such as RISC, and can cause interference and shut down gene activity.
Micro RNA is a form of ribonucleic acid and does not contain genetic information.
Functional Analysis of miRNA: miRNA and its Role in Human Disease Webinar Ser...QIAGEN
This slideshow highlights the use of miRNA mimics, inhibitors and target protectors to increase, decrease and adjust the cellular concentration of miRNA and disrupt specific miRNA–mRNA interactions. A ready-to-use screening tool for identifying miRNA targets and info on how to predict mRNA targets using miRNA expression data are also highlighted.
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
I have described in this presentation the critical points in the maturation of small non-coding RNA especially miRNA and its role in the development and diagnosis of specific psychiatric disorders
Mirna biogenesis, mechanism of action, isolation protocol, and quantification...SAIMA BARKI
The concise SlideShare presentation on the miRNA biogenesis, nomenclature, specific isolation protocols, the use of novel primers for preamplification purpose, and the comparison of different methods, qPCR based quantification along the guidance of the choice of sample and a novel technique for the different clinical samples.
Functional Analysis of miRNA: miRNA and its Role in Human Disease Webinar Ser...QIAGEN
This slideshow highlights the use of miRNA mimics, inhibitors and target protectors to increase, decrease and adjust the cellular concentration of miRNA and disrupt specific miRNA–mRNA interactions. A ready-to-use screening tool for identifying miRNA targets and info on how to predict mRNA targets using miRNA expression data are also highlighted.
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we
present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
I have described in this presentation the critical points in the maturation of small non-coding RNA especially miRNA and its role in the development and diagnosis of specific psychiatric disorders
Mirna biogenesis, mechanism of action, isolation protocol, and quantification...SAIMA BARKI
The concise SlideShare presentation on the miRNA biogenesis, nomenclature, specific isolation protocols, the use of novel primers for preamplification purpose, and the comparison of different methods, qPCR based quantification along the guidance of the choice of sample and a novel technique for the different clinical samples.
This slide is about the basics of mRNA-based therapy. The content includes: definition of mRNA, timeline of mRNA therapeutics, action mechanism and development strategies of mRNA drugs, therapeutic mRNA applications, and the related services provided by Creative Biolabs.
Outlines and exemplified how bioinformatics is particularily well to facilitate the discovery of oligonucleotide drugs.
One hour talk I gave a Aalborg University in 2010.
Macrophages as Targets in Cancer Immunotherapy - Creative BiolabsCreative-Biolabs
Due to the limitations and shortages of traditional cancer treatments, immunotherapy has become the most promising cancer treatment. Various cancer immunotherapy strategies have emerged. These include adoptive cellular immunotherapy, tumor vaccines, antibodies, immune checkpoint inhibitors, and small molecule inhibitors. Although most of these strategies are not meant to target macrophages directly or originally, macrophages contribute significantly to the final outcomes.
As a CRO company, Creative Biolabs offers first-in-class macrophage therapeutic development services. Please don’t hesitate to contact us if you are interested in our services or if you have any questions.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. A MICRORNA (ABBREVIATED MIRNA) IS A SMALL NON-
CODING RNA MOLECULE (CONTAINING ABOUT 22
NUCLEOTIDES) FOUND IN PLANTS, ANIMALS AND SOME
VIRUSES, THAT FUNCTIONS IN RNA SILENCING AND
POST-TRANSCRIPTIONAL REGULATION OF GENE
EXPRESSION.
3.
4.
5.
6. To inhibit the function of miRNAs, which are oncogenic miRNAs and over-expressed
in tumors, by applying the antisense oligonucleotides (ASOs) strategy, including
1-anti-miRNA oligonucleotides (AMOs),
2- miRNA antagomirs, locked-nucleic-acids antisense oligonucleotides (LNAs),
3-miRNA sponges, multiple-target anti-miRNA antisense oligodeoxyribonucleotides
(MTg-AMOs)
7.
8. Lentiviral vectors designed for clinical use are derived from HIV-1.
The vectors do not express any HIV genes and are replication
incompetent. After binding to the cell surface and internalization, the
RNA-genome is converted to DNA which then stably integrates into
the host cell chromosomal DNA. Finally, the genetic sequence of
interest- e.g. a shRNA, miRNA or gene-is transcribed by the cell‘s
intrinsic transcription machinery.
9. MicroRNA Function Targets Experimental Data Therapeutic Strategy
R
ef
er
en
ce
miR-145
Tumor
suppressor
ROCK1, MMP11, Rab27a, FSCN-1,
LASP1, MTDH, SENP1, E2F3,
MUC13, c-Myc
In vitro experiments in nasopharyngeal,
bladder, cervical, lung, liver, breast, gastric,
prostate cancer cell lines
In vivo experiments in prostate, pancreatic,
bladder cancers and multiple myeloma
Mimics
Vector-based (viral)
miR-34a
Tumor
suppressor
CDK6, SIRT1, E2F3, c-Met, Notch,
c-Myc, Fra-1, TPD52, c-SRC, Bcl-2,
MYCN
In vitro experiments in neuroblastoma,
glioblastoma and liver, prostate, colon,
breast cancer cell lines
In vivo experiments in multiple myeloma,
glioma and prostate xenografts in mice
Mimics
Vector-based (viral)
miR-29b
Tumor
suppressor
DNMT3A/3B, CDK6, MCL-1, TCL-1,
Bcl-2, KDM2A, MMP2,
TNFAIP3/A20, BCL2L2
In vitro experiments in glioblastomas, acute
myelocytic leukemia (AML), liver, lung,
gastric cancer cells
In vivo experiments in AML, liver and lung
cancers
Mimics
Vector-based (viral)
Let-7a
Tumor
suppressor
K-RAS, N-RAS, CDK6, CDC25A,
HMGA2, MYC, RTKN, E2F2
In vitro experiments in lung, gastric, breast
and colon cancer cells
In vivo experiments in breast and lung
cancers
Mimics
Vector-based (viral)
miR-340
Tumor
suppressor
ROCK1, MYO10, MET, CDH1, NF-
x03BA/B1, JAK1, EZH2
In vitro experiments in liver, glioma,
ovarian, breast, lung cancer cells
In vivo experiments in liver cancer
Mimics
Vector-based (viral)
miR495
Tumor
suppressor
MYB, Bim-1, MTA3, JAM-A, PRL-3
In vitro experiments in glioma, AML, lung,
breast, gastric, prostate cancer cells
In vivo experiments in endometrial, breast,
prostate cancers and leukemia
Mimics
Vector-based (viral)
miR155 Oncogene
SHIP-1, C/EBPβ, S0CS1, SOCS6,
FBXW7, ZDHHC2
In vitro experiments in liver cancer and
myeloid cells
In vivo experiments in pre-B
lymphoma/Leukemia and liver cancer
Antisense oligos
miR-MASK
Sponges
miR-21 Oncogene
PDCD4, PTEN, TPM1, FOXO1,
Rho-B, BTG-2, Cdc25A
In vitro experiments in multiple
myeloma, glioblastoma, lung, colon,
breast and liver cancer cells
In vivo experiments in multiple
myeloma
Antisense oligos
miR-MASK
Sponges or LNA
