1) DNA is transcribed into mRNA, which is then processed and exported from the nucleus to the cytoplasm.
2) In the cytoplasm, mRNA attaches to ribosomes to begin translation. Amino acids are activated and attached to specific tRNAs.
3) Translation occurs as tRNAs add amino acids to the growing polypeptide chain based on the mRNA codons. Ribosomes move along the mRNA during this process until a stop codon is reached and the completed protein is released.
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.
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.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
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 .
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
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.
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.
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.
1. From Gene to Phenotype- part 2
DNA
molecule
Gene 1
Gene 2
Gene 3
DNA strand
(template)
TRANSCRIPTION
mRNA
Protein
TRANSLATION
Amino acid
A C C A A A C C G A G T
U G G U U U G G C U C A
Trp Phe Gly Ser
Codon
3 5
3
5
2. Lecture Outline 11/7/05
• The central dogma:
– DNA->RNA->protein
• Various types of RNA
• The genetic code
• Mechanisms of translation
– Initiation, Elongation,Termination
Exam 3 is next Monday. It will cover mitosis and
meiosis, DNA synthesis, transcription, translation,
genetics of viruses.
(chapters 12, 13, 16, 17, part of 18)
3. Four types of RNA
• mRNA
– Messenger RNA, encodes the amino acid sequence of a
polypeptide
• rRNA
– Ribosomal RNA, forms complexes with protein called ribosomes,
which translate mRNA to protein
• tRNA
– Transfer RNA, transports amino acids to ribosomes during protein
synthesis
• snRNA
– Small nuclear RNA, forms complexes with proteins used in
eukaryotic RNA processing
5. Correspondence between exons and
protein domains
Gene
DNA
Exon 1 Intron Exon 2 Intron Exon 3
Transcription
RNA processing
Translation
Domain 3
Domain 1
Domain 2
Polypeptide
6. The genetic code
Second mRNA base
U C A G
U
C
A
G
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
AUU
AUC
AUA
AUG
GUU
GUC
GUA
GUG
Met or
start
Phe
Leu
Leu
lle
Val
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
ACU
ACC
ACA
ACG
GCU
GCC
GCA
GCG
Ser
Pro
Thr
Ala
UAU
UAC
UGU
UGC
Tyr Cys
CAU
CAC
CAA
CAG
CGU
CGC
CGA
CGG
AAU
AAC
AAA
AAG
AGU
AGC
AGA
AGG
GAU
GAC
GAA
GAG
GGU
GGC
GGA
GGG
UGG
UAA
UAG Stop
Stop UGA Stop
Trp
His
Gln
Asn
Lys
Asp
Arg
Ser
Arg
Gly
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
First
mRNA
base
(5
end)
Third
mRNA
base
(3
end)
Glu
7. The code is a triplet code
– the new boy saw the big cat eat the hot dog
• The first evidence for triplet code came from
deletion experiments
– the new boy saw the big cat eat the hot dog
– the neb oys awt heb igc ate att heh otd og
• Function could be restored by an insertion
nearby
– the new boy saw the big cat eat the hot dog
– the neb oys aaw the big cat eat the hot dog
8. The code is a triplet code
• . . . or by two more deletions to get it back
into the correct “reading frame”
– the new boy saw the big cat eat the hot dog
– the neb oys awt heb igc ate att heh otd og
– the neb osa wte big cat eat the hot dog
9. Deciphering the Code
• Your book tells how people used synthetic mRNAs
and in vitro translation to determine decipher the
codons.
• E.g. UUUUUUUU -> phenylalanine only
– UCUCUCUCUCU -> mix of leucine and serine
• Why is it a mixture?
10. The code is redundant
• Several different
codons encode
the same amino
acid
Second mRNA base
U C A G
U
C
A
G
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
AUU
AUC
AUA
AUG
GUU
GUC
GUA
GUG
Met or
start
Phe
Leu
Leu
lle
Val
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
ACU
ACC
ACA
ACG
GCU
GCC
GCA
GCG
Ser
Pro
Thr
Ala
UAU
UAC
UGU
UGC
Tyr Cys
CAU
CAC
CAA
CAG
CGU
CGC
CGA
CGG
AAU
AAC
AAA
AAG
AGU
AGC
AGA
AGG
GAU
GAC
GAA
GAG
GGU
GGC
GGA
GGG
UGG
UAA
UAG Stop
Stop UGA Stop
Trp
His
Gln
Asn
Lys
Asp
Arg
Ser
Arg
Gly
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
First
mRNA
base
(5
end)
Third
mRNA
base
(3
end)
11. The code is comma free
• No punctuation between words.
– Therefore deletions cause frameshifts
• It does have start and stop signals,
however.
– Start: AUG
– Stop: UAG, UAA, UGA
12. Translation: the basic concept
TRANSCRIPTION
TRANSLATION
DNA
mRNA
Ribosome
Polypeptide
Polypeptide
Amino
acids
tRNA with
amino acid
attached
Ribosome
tRNA
Anticodon
mRNA
Gly
A A A
U G G U U U G G C
Codons
5 3
13. The structure of transfer RNA (tRNA)
3
A
C
C
A
C
G
C
U
U
A
A
G
A
C
A
C
C
U
G
C
*
G U G U
C
U
GAG
G
U
A
A
A G
U
C
A
G
A
C
C
C G A G
A G G
G
G
A
C
U
C
A
U
U
U
A
G
G
C
G
5
Amino acid
attachment site
Hydrogen
bonds
Anticodon
*
*
*
*
*
*
*
*
*
*
*
16. P site (Peptide site)
E site (Exit site)
mRNA
binding site
Large
subunit
Small
subunit
E P A
A site (Acceptor site)
EPA model of a ribosome
17. Amino end Growing polypeptide
Next amino acid
to be added to
polypeptide chain
tRNA
mRNA
Codons
3
5
New amino acids are added to the
carboxyl end of the polypeptide
18. The initiation of translation
2
Initiator tRNA
mRNA
mRNA binding site
Small
ribosomal
subunit
Large
ribosomal
subunit
Translation initiation complex
P site
GDP
GTP
Start codon
1
U A C
A U G
E A
3
5
5
3
3
5 3
5
Small subunit binds just
upstream of start
Special initiator methionine
binds to the start codon (AUG)
The large subunit can now
bind to make the active
ribosome
19. Elongation
Amino end
of polypeptide
mRNA
tRNA with
appropriate
anticodon binds at A
site
Ribosome ready for
next aminoacyl tRNA
Translocaton.
Everything moves left
one notch. Polypeptide
is now at P. Empty
tRNA leaves the E site.
E
P A
E
P A
E
P A
E
P A
GDP
GTP
GTP
GDP
2
2
site site
5
3
3
2
1
TRANSCRIPTION
TRANSLATION
DNA
mRNA
Ribosome
Polypeptide
Peptide bond
formed. Growing
chain is now at A
21. 4
An aminoacyl-tRNA synthetase joins a specific
amino acid to a tRNA
Amino acid
ATP
Adenosine
Pyrophosphate
Adenosine
Adenosine
tRNA
P P P
P
P Pi
Pi
Pi
P
AMP
Appropriate
tRNA bonds to amino
Acid, displacing
AMP.
Active site binds the
amino acid and ATP.
1
3
Aminoacyl-tRNA
synthetase (enzyme)
Activated amino acid
is released by the enzyme.
23. Inhibition of protein synthesis
Toxin Mode of action Target
Puromycin
forms peptidyl-puromycin, prevents
translocation
Procaryotes
Tetracycline
blocks the A-site, prevents binding of aminoacyl
tRNAs
Procaryotes
Chloramphenicol blocks peptidyl transfer Procaryotes
Cycloheximide blocks peptidyl transferase Eucaryotes
Streptomycin inhibits initiation at high concentrations Procaryotes
Diphtheria toxin catalyzes ADP-ribosylation of residue in eEF2 Eucaryotes
Erythromycin binds to 50S subunit, inhibits translocation Procaryotes
Ricin
inactivates 60S subunit, depurinates an
adenosine in 23S rRNA
Eucaryotes
NOTE: Prokaryotes (this generally includes protein
synthesis in mitochondria and chloroplasts)
24. Summary of transcription and
translation in a eukaryotic cell
TRANSCRIPTION
RNA is transcribed
from a DNA template.
DNA
RNA
polymerase
RNA
transcript
RNA PROCESSING
In eukaryotes, the
RNA transcript (pre-
mRNA) is spliced and
modified to produce
mRNA, which moves
from the nucleus to the
cytoplasm.
Exon
RNA transcript
(pre-mRNA)
Intron
NUCLEUS
FORMATION OF
INITIATION COMPLEX
After leaving the
nucleus, mRNA attaches
to the ribosome.
CYTOPLASM
mRNA Growing
polypeptide
Ribosomal
subunits
Aminoacyl-tRNA
synthetase
Amino
acid
tRNA
AMINO ACID ACTIVATION
Each amino acid
attaches to its proper tRNA
with the help of a specific
enzyme and ATP.
Activated
amino acid
TRANSLATION
A succession of tRNAs
add their amino acids to
the polypeptide chain
as the mRNA is moved
through the ribosome
one codon at a time.
(When completed, the
polypeptide is released
from the ribosome.)
Anticodon
A A A
UG GUU UA U G
E A
Ribosome
1
5
5
3
Codon
2
3 4
5