Most bacteria are free-living organisms that grow by increasing
in mass and then divide by binary fission.
Growth and division are controlled by genes, the expression
of which must be regulated appropriately. Genes
whose activity is controlled in response to the needs of a
cell or organism are called regulated genes. All organisms
also have a large number of genes whose products
are essential to the normal functioning of a growing and
dividing cell, no matter what the conditions are. These
genes are always active in growing cells and are known as
constitutive genes or housekeeping genes; examples include
genes that code for the enzymes needed for protein
synthesis and glucose metabolism. Note that all genes are
regulated on some level. If normal cell function is impaired
for some reason, the expression of all genes, including
constitutive genes, is reduced by regulatory
mechanisms. Thus, the distinction between regulated
and constitutive genes is somewhat arbitrary.
Each cell in the human contains all the genetic material for the growth and development of a human
Some of these genes will be need to be expressed all the time
These are the genes that are involved in of vital biochemical processes such as respiration
Other genes are not expressed all the time
They are switched on an off at need
lac operon is a negatively controlled inducible operon.E.coli can use lactose as a source of carbon.
The enzymes required for the use of lactose as a source of carbon are synthesised only when the lactose is available as carbon source.
The lac operon is an example of nagatively controlled inducible operon.
Structure
The lac operon consists of 5 structural units.
Promoter
Operator
Structural genes
CAP binding sites
Regulatory gene
Gene regulation in eukaryotes in a nutshell covering all the important stages of gene regulation in eukaryotes at transcriptional level, translation level and post-translational level.
CBCS 4TH SEM ,
CHARGING, STRUCTURE AND FUNCTION OF tRNA,
AMINOACYL RNA SYNTHETASE(ASR) PROOFREADING AND EDITING
https://www.youtube.com/watch?v=YzOVMWYLiCE
Each cell in the human contains all the genetic material for the growth and development of a human
Some of these genes will be need to be expressed all the time
These are the genes that are involved in of vital biochemical processes such as respiration
Other genes are not expressed all the time
They are switched on an off at need
lac operon is a negatively controlled inducible operon.E.coli can use lactose as a source of carbon.
The enzymes required for the use of lactose as a source of carbon are synthesised only when the lactose is available as carbon source.
The lac operon is an example of nagatively controlled inducible operon.
Structure
The lac operon consists of 5 structural units.
Promoter
Operator
Structural genes
CAP binding sites
Regulatory gene
Gene regulation in eukaryotes in a nutshell covering all the important stages of gene regulation in eukaryotes at transcriptional level, translation level and post-translational level.
CBCS 4TH SEM ,
CHARGING, STRUCTURE AND FUNCTION OF tRNA,
AMINOACYL RNA SYNTHETASE(ASR) PROOFREADING AND EDITING
https://www.youtube.com/watch?v=YzOVMWYLiCE
Regulation of gene expression in prokaryotes finalICHHA PURAK
The power point presentation explains about regulation of gene expression in prokaryotes by means of Inducible and repressible operons with the help of Lactose(lac) operon and Tryptophan (trp)
Gene regulation is the process used to control the timing, location and amount in which genes are expressed. The process can be complicated and is carried out by a variety of mechanisms, including through regulatory proteins and chemical modification of DNA.
This is my first presentation share in this platform. Hope this is helpful for you! Here, I have tried to explain MECHANISM OF LAC OPERON in E.Coli in informative and crisp manner with simple language and few images.
Control of gene expression ppt
definition of gene expression
inducible gene expression
repressible gene expression
control of gene expression in eukaryotics .all the in information about this topic is include .
Gene regulation can be defined as any kind of alteration in the gene to give rise to a different expression which might result in a change in the synthesized amino acid sequence.”
Gene expression is basically the synthesis of the polypeptide chain encoded by a particular gene.
Therefore the expression of the gene can be quantified in terms of the amount of protein synthesised by the genes.
Heavy metal poisoning is caused by the accumulation of certain metals in the body due to exposure through food, water, industrial chemicals, or other sources. While your body needs small amounts of some heavy metals to function normally — such as zinc, copper, chromium, iron, and manganese — toxic amounts are harmful.
Interpretation of dna typing results and codis Neha Agarwal
An STR genotype is the allele, in the case of a homozygote, or alleles, in the
case of a heterozygote, present in a sample for a particular locus and is normally
reported as the number of repeats present in the allele. A full sample genotype
or STR profi le is produced by the combination of all of the locus genotypes into
a single series of numbers. This profi le is what is entered into a case report or
a DNA database for comparison purposes to other samples.
Sample collection and preservation of biological samplesNeha Agarwal
A preliminary survey should be carried out to evaluate potential evidence. In particular, the
recognition of evidence plays a critical role in solving or prosecuting crimes. The priority of the
potential evidence at crime scenes should be assessed based on each item’s relevance to the solution
of the case. Higher priority should be assigned to evidence with probative value to the case.
For example, the evidence related to a corpus delicti is considered to be of the highest priority.
Corpus delicti is a Latin term meaning “body of crime.” In Western law, it primarily refers to the
principle that in order for an individual to be convicted, it is necessary to prove the occurrence of the crime. In a forensic investigation, it also refers to the physical evidence proving that a crime was committed
Scope and significance of forensic chemistryNeha Agarwal
Forensic chemistry is the application of chemistry and its subfield, forensic toxicology, in a legal setting. A forensic chemist can assist in the identification of unknown materials found at a crime scene.[1] Specialists in this field have a wide array of methods and instruments to help identify unknown substances. These include high-performance liquid chromatography, gas chromatography-mass spectrometry, atomic absorption spectroscopy, Fourier transform infrared spectroscopy, and thin layer chromatography. The range of different methods is important due to the destructive nature of some instruments and the number of possible unknown substances that can be found at a scene. Forensic chemists prefer using nondestructive methods first, to preserve evidence and to determine which destructive methods will produce the best results.
Along with other forensic specialists, forensic chemists commonly testify in court as expert witnesses regarding their findings. Forensic chemists follow a set of standards that have been proposed by various agencies and governing bodies, including the Scientific Working Group on the Analysis of Seized Drugs. In addition to the standard operating procedures proposed by the group, specific agencies have their own standards regarding the quality assurance and quality control of their results and their instruments. To ensure the accuracy of what they are reporting, forensic chemists routinely check and verify that their instruments are working correctly and are still able to detect and measure various quantities of different substances.
Protection of critical information infrastructureNeha Agarwal
Information Infrastructure is the term usually used to describe the totality of inter-connected computers and networks, and information flowing through them. Certain parts of this Information Infrastructure, could be dedicated for management / control etc of infrastructure providers’ e.g. Power generation, Gas/oil pipelines, or support our economy or national
fabric e.g. Banking / Telecom etc. The contribution of the services supported
by these infrastructures, and more importantly, the impact of any sudden
failure or outage on our National well being or National Security marks them as being Critical.
By extension, information infrastructure supporting the operations of Critical Infrastructure (CI) marks this as Critical Information infrastructure (CII). These Networks operate/monitor and control important Governmental and Societal functions and services including, but not limited to, Power (Generation/transmission/ distribution etc), Telecommunication (mobile/landline/internet etc), Transportation (Air/land/rail/sea etc), Defence etc. These CII are becoming increasingly dependent on their information infrastructure for information management, communication and control functions.
“Microbial forensics” has been defined as “a scientific discipline dedicated to analyzing evidence
from a bioterrorism act, biocrime, or inadvertent microorganism/toxin release for attribution
purposes” (Budowle et al., 2003). This emerging discipline is still in the early stages of
development and faces substantial scientific challenges to provide a robust suite of technologies
for identifying the source of a biological threat agent and attributing a biothreat act to a particular
person or group. The unlawful use of biological agents poses substantial dangers to individuals,
public health, the environment, the economies of nations, and global peace. It also is likely that
scientific, political, and media-based controversy will surround any investigation of the alleged
use of a biological agent, and can be expected to affect significantly the role that scientific
information or evidence can play. For these reasons, building awareness of and capacity in
microbial forensics can assist in our understanding of what may have occurred during a biothreat
event, and international collaborations that engage the broader scientific and policy-making
communities are likely to strengthen our microbial forensics capabilities. One goal would be to
create a shared technical understanding of the possibilities—and limitations—of the scientific
bases for microbial forensics analysis._ NCBI
Forensic science utilizes scientific principles to support or negate theories surrounding physical evidence found at a crime scene. As such, forensic scientists analyze evidence gathered or received from crime scenes and present their findings based the results of their analyses.
A forensic science job description may appear distinctly different depending on the area of forensic science being practiced. This is because forensic science is a rather broad field and thus encompasses a number of specialties, all of which are rooted in the natural sciences.
The error (or disturbance) of an observed value is the deviation of the observed value from the (unobservable) true value of a quantity of interest (for example, a population mean), and the residual of an observed value is the difference between the observed value and the estimated value of the quantity of interest (for example, a sample mean).
Suppose there is a series of observations from a univariate distribution and we want to estimate the mean of that distribution (the so-called location model). In this case, the errors are the deviations of the observations from the population mean, while the residuals are the deviations of the observations from the sample mean.
A statistical error (or disturbance) is the amount by which an observation differs from its expected value, the latter being based on the whole population from which the statistical unit was chosen randomly. For example, if the mean height in a population of 21-year-old men is 1.75 meters, and one randomly chosen man is 1.80 meters tall, then the "error" is 0.05 meters; if the randomly chosen man is 1.70 meters tall, then the "error" is −0.05 meters. The expected value, being the mean of the entire population, is typically not observable, and hence the statistical error cannot be observed either.
It is over 60 years since Hodgkin and
Huxley1 made the first direct recording of
the electrical changes across the neuronal
membrane that mediate the action
potential. Using an electrode placed inside a
squid giant axon they were able to measure a
transmembrane potential of around 260 mV
inside relative to outside, under resting
conditions (this is called the resting membrane
potential). The action potential is a
transient (,1 millisecond) reversal in the
polarity of this transmembrane potential
which then moves from its point of initiation,
down the axon, to the axon terminals. In a
subsequent series of elegant experiments
Hodgkin and Huxley, along with Bernard
Katz, discovered that the action potential
results from transient changes in the permeability
of the axon membrane to sodium (Na+)
and potassium (K+) ions. Importantly, Na+ and
K+ cross the membrane through independent
pathways that open in response to a change
in membrane potential.
As testimony to their pioneering work, the
fundamental mechanisms described by
Hodgkin, Huxley and Katz remain applicable
to all excitable cells today. Indeed, the
predictions they made about the molecular
mechanisms that might underlie the changes
in membrane permeability showed remarkable
foresight. The molecular basis of the action
potential lies in the presence of proteins
called ion channels that form the permeation
pathways across the neuronal membrane.
Although the first electrophysiological
recordings from individual ion channels were
not made until the mid 1970s,2 Hodgkin and
Huxley predicted many of the properties now
known to be key components of their
function: ion selectivity, the electrical basis
of voltage-sensitivity and, importantly, a
mechanism for quickly closing down the
permeability pathways to ensure that the
action potential only moves along the axon in
one direction.
It is over 60 years since Hodgkin and
Huxley1 made the first direct recording of
the electrical changes across the neuronal
membrane that mediate the action
potential. Using an electrode placed inside a
squid giant axon they were able to measure a
transmembrane potential of around 260 mV
inside relative to outside, under resting
conditions (this is called the resting membrane
potential). The action potential is a
transient (,1 millisecond) reversal in the
polarity of this transmembrane potential
which then moves from its point of initiation,
down the axon, to the axon terminals. In a
subsequent series of elegant experiments
Hodgkin and Huxley, along with Bernard
Katz, discovered that the action potential
results from transient changes in the permeability
of the axon membrane to sodium (Na+)
and potassium (K+) ions. Importantly, Na+ and
K+ cross the membrane through independent
pathways that open in response to a change
in membrane potential.
As testimony to their pioneering work, the
fundamental mechanisms described by
Hodgkin, Huxley and Katz remain applicable
to all excitable cells today. Indeed, the
predictions they made about the molecular
mechanisms that might underlie the changes
in membrane permeability showed remarkable
foresight. The molecular basis of the action
potential lies in the presence of proteins
called ion channels that form the permeation
pathways across the neuronal membrane.
Although the first electrophysiological
recordings from individual ion channels were
not made until the mid 1970s,2 Hodgkin and
Huxley predicted many of the properties now
known to be key components of their
function: ion selectivity, the electrical basis
of voltage-sensitivity and, importantly, a
mechanism for quickly closing down the
permeability pathways to ensure that the
action potential only moves along the axon in
one direction.
COMPLEMENT - A group of serum proteins which can be activated (= "fixed") by antigen-antibody complexes or other substances, which may result in lysis of a microbial target, or a variety of other biological effects important in both innate and adaptive immunity. (The majority of these proteins are produced by the liver.)The complex of serum proteins known as COMPLEMENT plays key roles in the lytic and inflammatory properties of antibodies. The CLASSICAL pathway is initiated
by antigen-antibody complexes (via complement components C1, C4, and C2), while the activation of the ALTERNATE pathway (via components B, D and P), and the MBLECTIN ("mannan-binding lectin") pathway may be initiated by other substances independently of adaptive immune responses; all three pathways share those complement components involved in the inflammatory and lytic consequences, namely C3, C5, C6,
C7, C8 and C9. The INFLAMMATION which is a consequence of complement fixation is illustrated by the manifestations of SERUM SICKNESS, and complement is also seen
to be central to the normal process of clearing immune complexes, which is important in preventing IMMUNE COMPLEX DISEASE.
The term river system refers to a ‘river along with its tributaries’.
Based on their source, the Indian River system is classified in to - Himalayan Rivers and Peninsular Rivers.
The Himalayan Rivers, as the name suggests originate from the Himalayas and flow through the Northern Plains.
The major Himalayan River systems are
The Indus River System,
The Ganga River System
The Yamuna River System
The Brahmaputra River System
Peninsular River System or Peninsular Drainage emerges mainly from the Western Ghats. Since the Western Ghats form a ‘water divide’, these rivers either flow eastwards into the Bay of Bengal or into the Arabian Sea towards the west. Peninsular Rivers are basically ‘rain fed’ rivers.
The major Peninsular River Systems are:
Mahanadi
Godavari
Krishna
Cauvery
Drain into Bay of Bengal as they flow eastwards on the plateau and make ‘deltas’ at their mouths; whereas Narmada
Tapti - the west flowing rivers fall into the Arabian Sea and make ‘estuaries’.
not originate in glaciers, but are rain fed rivers. These rivers reduce considerably or dry up during summers.
Sericulture is the silk producing agro-industry
India is the second largest silk producing country in the world after china.
Sericulture or silk farming is the rearing of silkworm for the production of silk
Silk is known as queen of textile and biosteel because of its strength
A Chinese tale of the discovery of the silkworm’s silk was by an ancient empress Lei Zu , the wife of the emperor.
She was drinking tea under tree, when a silk cocoon fell into her tea cup and the hot tea loosened the long strand of silk
As she it out, and started to wrap the silk thread around her flinger, she felt the warm sensation
When silk ran out, an larva appeared. She realized that it was this larva that produces the silk
Soon, she taught this to people and it became wide spread
Echinococcus granulosus, also called hydatid worm belongs to class Cestoda
It causes cystic echinococcosis in livestock and humans being intermediate hosts and parasitize the small intestines of adult canids
It is a zoonotic disease
Definitive hosts are carnivorous predators like dogs, wolves, foxes and lions. While sheep, goat, cattle, pigs and rodents are intermediate hosts. Birds and arthropods act as mechanical vectors
Krebs cycle or tricarboxylic cycle or citric acid cycleNeha Agarwal
The citric acid cycle is the final common pathway for the oxidation of fuel molecules — amino acids, fatty acids, and carbohydrates.
Hans Adolf Krebs. Biochemist; born in Germany. Worked in Britain. His discovery in 1937 of the ‘Krebs cycle’ of chemical reactions was critical to the understanding of cell metabolism and earned him the 1953 Nobel Prize for Physiology or Medicine.
Induced breeding is a technique where organism is stimulated by particular hormone or other synthetic hormone or by providing condition, introduced to breed in captive condition.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
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/
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
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.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
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.
2. Gene is the segment of DNA that controls all
traits of organism that may be
physical or metabolical. In information
encoded in DNA is transcribed into RNA
and then translate into proteins. The ability of
cell to switch the genes on and off
is of fundamental importance because it
enables the cell to respond to the
changing environment and it is the basis of
cell differentiation. So we can say
that:
2
3. “Gene Regulation is a process in which
a cell determines which genes it
will express and when.”
Regulation of gene expression includes a wide
range of mechanisms that are used by the cell
to increase or decrease the production of
specific gene products (protein or RNA).
Sophisticated programs of gene expression
are widely observed in biology to trigger
developmental pathways, respond to
environmental stimuli or adapt to new food
sources.
3
4. Discovery:
The first discovery of a gene regulation system is
widely considered to be the identification in 1961 of
the lac operon, discovered by Jacques Monod, in
which some enzymes involved in lactose metabolism
are expressed by the genome of E.Coli only in the
presence of lactose and absence of glucose.
Furthermore, in 1953, Jacques Monod discovered
enzyme repression. He observed the presence of
tryptophan in medium of E.Coli which repressed the
synthesis of tryptophan synthetase and then further
studies showed that all the enzymes, present in
tryptophan biosynthetic pathway are simultaneously
repressed in the presence of end product.4
5. Gene Regulation in Prokaryotes:
The rate of expression of bacterial gene is controlled mainly
at level of transcription. Regulation can occur at both the
initiation and termination of mRNA synthesis because
bacteria obtain their food from the medium that
immediately surrounds them. Their regulation mechanisms
are designed to adapt quickly to the changing environment.
If a gene is not transcribed then the gene product and
ultimately the phenotype will not be expressed. In contrast,
eukaryotes have much complex and larger genome and cells
of higher organisms are surrounded by constant internal
milieu. The ability of such cells to respond to hormones and
to impulse in nervous system is thus comparatively more
important that the ability to respond rapidly in the presence
of certain nutrients.
5
6. Principles of Transcriptional Regulation:
6
Gene Expression Is Controlled by Regulatory Proteins:
Genes are very often controlled by extracellular signals, in the case of
bacteria, this typically means molecules present in the growth medium.
These signals are communicated to genes by regulatory proteins, which
come in two types: positive regulators, or activators; and negative
regulators, or repressors. Typically these regulators are DNA binding
proteins that recognize specific sites at or near the genes they control. An
activator increases transcription of the regulated gene; repressors
decrease or eliminate that transcription. First, RNA polymerase binds to
the promoter in a closed complex (in which the DNA strands remain
together). The polymerase-promoter complex then undergoes a transition
to an open complex in which the DNA at the start site of transcription is
unwound and the polymerase is positioned to initiate transcription. This is
followed by promoter escape, or clearance, the step in which polymerase
leaves the promoter and starts transcribing.
7. 7
Promoter gene Operator gene Structural gene
Where RNA
polymerase binds
Where repressor
molecule bind
Group of different genes
encoding for specific
proteins
11. Operon is the group of the genes
that are nest to each other in DNA
and that can be controlled in a
unified manner. The genes of the
structural enzymes are always
transcribed together into a single
polycistronic lac mRNA which
explains why they are always
expressed together.
11
12. Lac operon is induced 1000 folds by lactose. The cell is an
energy efficient unit that makes protein it needs. E. coli has
about three thousand protein encoding genes but only a set
of them is expressed at any one time. The best illustration of
this efficiency is provided by the enzymes involved in the
utilization of disaccharide lactose. The synthesis of these
enzymes may be induced up to 1000 folds in respond to the
addition of lactose to the culture media. Regulation by
enzyme induction has been found in many other bacterial
systems that degrade sugars, amino acids and lipids. In these
systems, the availability of the substrates stimulates the
production of enzymes involved in its degradation. Induction
is the production of a specific enzyme (or set of enzymes) in
response to the presence of a substrate. The lac operon is a
inducible system.
12
13. Lactose as a Carbon Source for E. coli
E. coli can grow in a simple medium containing salts
(including a nitrogen source) and a carbon source such
as glucose. The energy for biochemical reactions in the
cell comes from glucose metabolism. The enzymes required
for glucose metabolism are coded for by constitutive genes.
If lactose is provided to E. coli as a carbon source instead of
glucose, a number of enzymes that are required to
metabolize lactose are rapidly synthesized. (A similar series
of events, each involving a sugar-specific set of enzymes, is
triggered by other sugars as well.) The enzymes are
synthesized because the genes that code for them become
actively transcribed in the presence of the sugar; the same
genes are inactive if the sugar is absent.
In other words, the genes are regulated genes whose
products are needed only under certain conditions.13
14. Structure of the lac operon:
1.The lac operon consists of the three structural genes, a
promoter, regulator, terminator and an operator.
2 These three structural genes are; lac Z, lac Y and lac A.
3 Lac Z encode β-galactosidase, an intracellular enzyme that
cleaves the disaccharide lactose into glucose and
galactose and catalysis isomerization of lactose to
allolactose,
4 Lac Y encode β-galactosidase permease, an inner
membrane bound symporter that pumps lactose into the
cell using a proton gradient.
5 Lac A encodes β-galactosidase transacetylase, an enzyme
that transfer an ecetyl group from acetyl-CoA to β-
galactosides.
6 Only lac Z and lac Y are necessary for lactose catabolism.14
16. The three enzymes required for the utilization of the lactose are β-galactosidase, β-
galactosidase pemease and β-galactosidase transacetylase.
The expression of lac operon is regulated by lac repressor.
The repressor binds closely and specifically to short DNA segment called “operator”,
which is in location very close to the β-galactosidase gene.
The affinity of the repressor to bind to the operator is regulated by inducer,
a small molecule that can bind to the repressor. The natural inducer of lactose is
allolactose, a metabolite of lactose. However, the analogue IPTG (isopropyl
thiogalactosidase) is a more powerful inducer that is preferred in the laboratory.
Each subunit of the repressor has one binding site for inducer and upon binding it
undergoes a conformational change by which it becomes unable to bind to the
operator. In this way the presence of the inducer permits transcription of lac
operon which is no longer block by the reppressor.
Promoter is the DNA segment to which RNA polymerase binds when initiating
transcription. Repressor binds within the promoter and prevents attachment
of RNA polymerase
The way in which the repressor work is very simple.
They bind within the promoter and prevents the attachment of RNA polymerase
16
20. E. coli has certain operons and other gene systems that
enable it to manufacture any amino acid that is lacking
in the medium in which it is placed, so that it can grow
and reproduce. When an amino acid is present in the
growth medium, though, the genes encoding the enzymes
for biosynthetic pathway for that amino acid are
turned off. Unlike the lac operon, wherein gene activity
is induced when a chemical (lactose) is added to the
medium, in this case gene activity is repressed when a
chemical (an amino acid) is added. We call amino
acid
biosynthesis operons controlled in this way repressible
operons. In general, operons for anabolic (biosynthetic)
pathways are repressed (turned off) when the end
product
is readily available
20
21. In tryptophan operon, regulation of
transcription occur at initiation and
termination. In E. coli the five contiguous trp
genes encode enzymes that synthesize the
amino acid tryptophan. These genes are
expressed efficiently only when tryptophan is
limiting.
21
22. 22
Five structural genes (A–E)
The promoter and operator regions are
upstream from the trpE gene.
Between the promoter–operator region and trpE
is a short region called trpL, the leader region.
Within trpL, close to trpE, is an attenuator site
(att) that plays an important role in the regulation
of the trp operon.
The regulatory gene for the trp operon is trpR,
located some distance from the operon. The
product of trpR is an aporepressor protein
The entire trp operon is approximately 7,000 base
pairs long. Transcription of the operon results in
the production of a polycistronic mRNA for the
five structural genes.
26. Regulation of the trp Operon
Two regulatory mechanisms are involved in controlling
the expression of the trp operon. One mechanism uses a
repressor–operator interaction, and the other determines
whether initiated transcripts include the structural genes
or are terminated before those genes are reached.
Expression of the trp Operon in the Presence of
Tryptophan.
The product of trpR is an aporepressor protein, which is basically
an inactive repressor that alone cannot bind to the operator. When
tryptophan is abundant within the cell, it interacts with the
aporepressor and converts it to an active Trp repressor.
The active Trp repressor binds to the operator and prevents the
initiation of transcription of the trp operon protein-coding genes by
RNA polymerase. As a result, the tryptophan biosynthesis enzymes
are not produced. By repression, transcription of the trp operon can
be reduced about seventy-fold.26
27. Expression of the trp Operon in the Presence of
Low Concentrations of Tryptophan.
The second regulatory mechanism is involved in the expression of
the trp operon under conditions of tryptophan starvation or
tryptophan limitation. Under severe tryptophan starvation, the trp
genes are expressed maximally; under less severe starvation
conditions, the trp genes are expressed at less than maximal
levels. This is accomplished by a mechanism that controls the
ratio of full-length transcripts that include the five trp
structural genes to short, 140-bp transcripts that have
terminated at the attenuator site within the trpL region. The
short transcripts are terminated by a process called attenuation.
The proportion of the transcripts that include the structural genes is
inversely related to the amount of tryptophan in the cell; the more
tryptophan there is, the greater is the proportion of short transcripts.
Attenuation can reduce transcription of the trp operon by a
factor of 8 to 10. Thus, repression and attenuation together
can regulate the transcription of the trp operon by a factor of
about 560 to 700.27
28. Mechanism:
The genes are controlled by a repressor, just as the lac genes
are, but in this case the ligand that controls the activity of
that repressor (tryptophan) acts not as an inducer but as a
co-repressor. That is, when tryptophan is present, it binds
the trp repressor and induces a conformational change in
that protein, enabling it to bind the trp operator and prevent
transcription. When the tryptophan concentration is low, the
trp repressor is free of its co-repressor and vacates its
operator, allowing the synthesis of trp mRNA to commence
from the adjacent promoter. Surprisingly, however, once
polymerase has initiated a trp mRNA molecule it does not
always complete the full transcript. Indeed, most messages
are terminated prematurely before they include even the
first trp gene (trpE),unless a second and novel device
confirms that little tryptophan is available to the cell.28
30. Prokaryotic Regulation of Genes
30
Regulating Biochemical
Pathway for Tryptophan
Synthesis.
1. Produce something that
will interfere with the
function of the enzyme in
the pathway.
2. Produce a gene regulator
that can inhibit the
transcription of one
biochemical pathway
enzymes.
31. Attenuation
31
When tryptophan levels are high, RNA polymerase that has initiated
transcription pauses at a specific site, and then terminates befor
getting to trpE. When tryptophan is limiting, however, that
termination does not occur and polymerase reads through the trp
genes. Attenuation, and the way it is overcome, rely on the close
link between transcription and translation in bacteria, and on the
ability of RNA to form alternative structures through intramolecular
base pairing. The key to understanding attenuation came from
examining the sequence of the 5’ end of trp operon mRNA. This
analysis revealed that 161 nucleotides of RNA are made from the
tryptophan promoter before RNA polymerase encounters the first
codon of trpE. Near the end of the sequence, and before trpE, is a
transcription terminator, composed of a characteristic hairpin loop
in the RNA, followed by eight uridine residues. At this so-called
attenuator, RNA synthesis usually stops yielding a leader RNA 139
nucleotides long.
Editor's Notes
In all cells, there are genes that code for proteins. It would be wasteful if genes were expressed when there is not a need for the protein product.
Example - why make enzymes used to break glycogen into glucose if the cell has a reservoir of glucose molecules? OR if the cell has no glycogen?
Regulating Prokaryotic Genes
Prokaryotic regulation is different from eukaryotic regulation.
Prokaryotic gene regulation tends to be negative. Meaning that the gene is usually activated unless some regulator inhibits it or deactivates it.
Eukaryotic gene regulation is usually positive. Meaning that the gene is usually deactivated unless a regulator activates it or turns it “on”.