This document provides an overview of apoptosis (programmed cell death) at the cellular level. It discusses how apoptosis can be initiated through either the intrinsic or extrinsic pathway. The intrinsic pathway involves signals within the cell like mitochondrial membrane permeability, while the extrinsic pathway involves death receptors on the cell surface and their ligands. Key proteins and complexes involved in each pathway are caspase enzymes and the apoptosome. Research on apoptosis has increased understanding of diseases like cancer that involve deregulated cell proliferation and death.
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
here is some information about autophagy, how it happend, when it happend and it's mechanism.
and some information about it's effect on cancer and some disorders.
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
Cytokine Receptors, Mohammad Mufarreh AliMMufarreh
A detailed description of the nature, types, and mechanisms of action of cytokine receptors.
Describes the different functions of cytokines and their role in the regulation of the immune response.
Cytokine receptor signalling and their regulation and the role of cytokines in disease is also covered briefly.
Cell cycle and Regulation
* cell Division is occur in every human but these have certaint check point to preventing from the forming the defective cell or cancerious cell.
MAPK Signaling pathway (Mitogen-activated protein kinase), how the pathway helps in regulation of mitosis, It's activation and inactivation inside the cell, roles of MAPK pathway in cancerous cell, different classes of MAP kinase in human
here is some information about autophagy, how it happend, when it happend and it's mechanism.
and some information about it's effect on cancer and some disorders.
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are mutated or expressed at high levels. Most normal cells undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered.
Cytokine Receptors, Mohammad Mufarreh AliMMufarreh
A detailed description of the nature, types, and mechanisms of action of cytokine receptors.
Describes the different functions of cytokines and their role in the regulation of the immune response.
Cytokine receptor signalling and their regulation and the role of cytokines in disease is also covered briefly.
Cell cycle and Regulation
* cell Division is occur in every human but these have certaint check point to preventing from the forming the defective cell or cancerious cell.
Hi! I am Komal Sankaran, M.Sc. Biotechnology (Pune University Gold Medalist, 2013), CSIR-NET SPM fellow (Jun- 2014, 4th rank), CSIR-NET- LS (Dec 2013, 2nd rank), DBT JRF category- I. Please contact if anyone is interested in Life Sciences CSIR-NET coaching in Pune (Khadki area).
Email- komalsan91@gmail.com
Apoptosis is a
-pathway of cell death that is
-induced by an internally regulated program
-in which cells destined to die activate intrinsic enzymes that --degrade the cells’ own nuclear DNA and also nuclear and cytoplasmic proteins
-With minimal host reaction.
Content-
1. Background
2. Introduction
3. Difference between apoptosis and necrosis
4. Apoptosis in biologic processes
5. Apoptosis in pathologic processes
6. Morphologic features
7. Techniques to identify and count apoptotic cells
8. Biochemical changes
9. Molecular mechanism of apoptosis
10. Recent advancement and emerging trends in apoptosis
11. References
Need for Defibrillators
Types of Defibrillators
Defibrillators Electrodes
Principle of defibrillation
Working of AED
Precaution in defibrillation process
Molecular interaction, Regulation and Signalling receptors and vesiclesAnantha Kumar
1. Overview of Extracellular signalling
2. Signalling molecules operate over various distance in animals
3.Endocrine Signalling
4.Paracrine Signalling
5.Autocrine Signalling
6. Signalling by Plasma membrane attached proteins
7.Receptors
8 Properties of receptors
9.Cell surface receptors belong to four major classes
10.Signal transduction Mechanism
11. Second messenger
12. Contraction of skeletal Muscle cells mechanism
Inhibiting Signalling pathways through Rational Drug designAnantha Kumar
1.Rational drug design
2.Transforming growth factor beta signalling as a model for signalling cascade amenable to drug development
3.Intracellular signalling mechanism
4. TGF-beta inhibitors screening
5.Conclusion
Introduction
Oncogenes and Tumor Suppressor Genes
Overexpression of cyclin D1
Loss of p16 Function
Loss of signalling Contributes to abnormal cell proliferation and malignancy
Summary
Questions
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 .
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.
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.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
2. INTRODUCTION
• Apoptosis (from Ancient Greek ἀπόπτωσις "falling off")
is a process of programmed cell death that occurs in
multicellular organisms.
• Biochemical events lead to characteristic cell changes
(morphology) and death.
• These changes include blebbing, cell shrinkage, nuclear
fragmentation, chromatin condensation, chromosomal
DNA fragmentation, and global mRNA decay.
• Between 50 and 70 billion cells die each day due to
apoptosis in the average human adult.
• For an average child between the ages of 8 and 14,
approximately 20 to 30 billion cells die a day.
3. Cont..
• Apoptosis can be initiated through one of two
pathways.
• In the intrinsic pathway the cell kills itself
because it senses cell stress, while in
the extrinsic pathway the cell kills itself
because of signals from other cells.
• Both pathways induce cell death by
activating caspases, which are proteases, or
enzymes that degrade proteins.
4. Cont..
• Research on apoptosis has increased
substantially since the early 1990s
• Excessive apoptosis causes atrophy, whereas
an insufficient amount results in uncontrolled
cell proliferation, such as cancer.
• Some factors like Fas receptors and caspases
promote apoptosis, while some members of
the Bcl-2 family of proteins inhibit apoptosis.
5. DISCOVERY
• German scientist Karl Vogt was first to describe the
principle of apoptosis in 1842.
• In 1885, anatomist Walther Flemming delivered a more
precise description of the process of programmed cell
death
• The 2002 Nobel Prize in Medicine was awarded
to Sydney Brenner, Horvitz and John E. Sulston for their
work identifying genes that control apoptosis.
• The genes were identified by studies in the
nematode C. elegans and homologues of these genes
function in humans to regulate apoptosis.
6. John E. Sulston won the Nobel Prize in
Medicine in 2002, for his pioneering research
on apoptosis
7.
8. Intrinsic pathway
• The mitochondria are essential to multicellular life.
• Without them, a cell ceases to respire aerobically and
quickly dies.
• This fact forms the basis for some apoptotic pathways.
• Apoptotic proteins that target mitochondria affect
them in different ways.
• They may cause mitochondrial swelling through the
formation of membrane pores, or they may increase
the permeability of the mitochondrial membrane and
cause apoptotic effectors to leak out.
9. Cont..
• They are very closely related to intrinsic
pathway, and tumors arise more frequently
through intrinsic pathway than the extrinsic
pathway because of sensitivity.
• Mitochondrial proteins known as SMACs
(second mitochondria-derived activator
of caspases) are released into the
cell's cytosol following the increase in
permeability of the mitochondria membranes
10. Cont..
• SMAC binds to proteins that inhibit
apoptosis (IAPs) thereby deactivating them,
and preventing the IAPs from arresting the
process and therefore allowing apoptosis to
proceed.
• IAP also normally suppresses the activity of a
group of cysteine proteases called caspases,
which carry out the degradation of the cell.
11. Cont..
• Cytochrome c is also released from mitochondria
due to formation of a channel.
• The mitochondrial apoptosis-induced
channel (MAC), in the outer mitochondrial
membrane and serves a regulatory function as it
precedes morphological change associated with
apoptosis.
• Once cytochrome c is released ,It binds with
Apoptotic protease activating factor – 1 (Apaf-1)
and ATP, which then bind to pro-caspase-9 to
create a protein complex known as
an apoptosome.
12. Cont..
• The apoptosome cleaves the pro-caspase to its active
form of caspase-9, which in turn activates the
effector caspase-3.
• MAC (not to be confused with the membrane attack
complex formed by complement activation, also
commonly denoted as MAC)
• Also called "Mitochondrial Outer Membrane
Permeabilization Pore" is regulated by various proteins,
such as those encoded by the mammalian Bcl-2
family of anti-apoptopic genes, the homologs of
the ced-9 gene found in C. elegans.
13. Cont..
• Bcl-2 proteins are able to promote or inhibit
apoptosis by direct action on MAC/MOMPP
• Bax and/or Bak form the pore, while Bcl-2, Bcl-
xL or Mcl-1 inhibit its formation
14.
15. Extrinsic pathway
• Two theories of the direct initiation of
apoptotic mechanisms in mammals have been
suggested:
1. The TNF-induced (tumor necrosis factor)
model
2. The Fas-Fas ligand-mediated model, both
involving receptors of the TNF
receptor (TNFR) family coupled to extrinsic
signals.
16. TNF path
TNF-alpha is a cytokine produced mainly by
activated macrophages
IT is the major extrinsic mediator of apoptosis.
Most cells in the human body have two
receptors for TNF-alpha:
A. TNFR1
B. TNFR2.
17. Cont..
• The binding of TNF-alpha to TNFR1 initiate the
pathway that leads to caspase activation via the
intermediate membrane proteins TNF receptor-
associated death domain (TRADD) and Fas-
associated death domain protein (FADD
• cIAP1/2(cellular inhibitor apoptosis protein 1) can
inhibit TNF-α signaling by binding to TRAF2.
• FLIP(Cellular FLICE (FADD-like IL-1β-converting
enzyme)-inhibitory protein (c-FLIP) inhibits the
activation of caspase-8.
18. Cont..
• However, signalling through TNFR1 might also
induce apoptosis in a caspase-independent
manner.
• The link between TNF-alpha and apoptosis
shows why an abnormal production of TNF-
alpha plays a fundamental role in several
human diseases, especially in autoimmune
diseases.
19.
20. Fas path
• The fas receptor (First apoptosis signal) – (also
known as Apo-1 or CD95) is a transmembrane
protein of the TNF family which binds the Fas
ligand (FasL).
• The interaction between Fas and FasL results
in the formation of the death-inducing
signaling complex (DISC), which contains the
FADD, caspase-8 and caspase-10.
21. Cont..
• In some types of cells (type I), processed
caspase-8 directly activates other members of
the caspase family, and triggers the execution
of apoptosis of the cell.
• In other types of cells (type II), the Fas-DISC
starts a feedback loop that spirals into
increasing release of proapoptotic factors
from mitochondria and the amplified
activation of caspase-8.
