A new effector pathway links ATM kinase with the DNA damage responseCostas Demonacos
The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) phosphorylate a limited number of downstream protein targets in response to DNA damage. Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Strap remains localized in the cytoplasm in cells derived from ataxia telangiectasia individuals with defective ATM, as well as in cells expressing a Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus reinstates protein stabilization and activates the DNA damage response. These results indicate that the nuclear accumulation of Strap is a critical regulator in the damage response, and argue that this function can be assigned to ATM through the DNA damage-dependent phosphorylation of Strap.
A new effector pathway links ATM kinase with the DNA damage responseCostas Demonacos
The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) phosphorylate a limited number of downstream protein targets in response to DNA damage. Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Strap remains localized in the cytoplasm in cells derived from ataxia telangiectasia individuals with defective ATM, as well as in cells expressing a Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus reinstates protein stabilization and activates the DNA damage response. These results indicate that the nuclear accumulation of Strap is a critical regulator in the damage response, and argue that this function can be assigned to ATM through the DNA damage-dependent phosphorylation of Strap.
PhD poster presented at; the University of Nottingham Pharmacy School 2nd Year PhD Poster Day, the British Association of Cancer Research (BACR) Special Conference: Advances in Cancer Drug Discovery, the University of Nottingham - Faculty of Medicine and Health Sciences Review of Research 2009 and the University of Nottingham Graduate School Poster Day (prize winner). I also presented this poster to the Vitae Midlands Hub Regional Poster Competition 2009 where I represented the University of Nottingham.
Presentation made by Dr. Simon Alberti on October 30, 2015 at the Alzforum-hosted live webinar titled "Fluid Business: Could “Liquid” Protein Herald Neurodegeneration?"
More information and the recording of the session available at http://www.alzforum.org/webinars/fluid-business-could-liquid-protein-herald-neurodegeneration
CRISPR- Trap: a clean approach for the generation of gene knockouts and gene replacements in human cells.- a paper is taken for lab presentation. A very good technique having advantages over conventional KO approaches and allow for the generation of clean CRISPR/ Cas9- based KOs.
PhD poster presented at; the University of Nottingham Pharmacy School 2nd Year PhD Poster Day, the British Association of Cancer Research (BACR) Special Conference: Advances in Cancer Drug Discovery, the University of Nottingham - Faculty of Medicine and Health Sciences Review of Research 2009 and the University of Nottingham Graduate School Poster Day (prize winner). I also presented this poster to the Vitae Midlands Hub Regional Poster Competition 2009 where I represented the University of Nottingham.
Presentation made by Dr. Simon Alberti on October 30, 2015 at the Alzforum-hosted live webinar titled "Fluid Business: Could “Liquid” Protein Herald Neurodegeneration?"
More information and the recording of the session available at http://www.alzforum.org/webinars/fluid-business-could-liquid-protein-herald-neurodegeneration
CRISPR- Trap: a clean approach for the generation of gene knockouts and gene replacements in human cells.- a paper is taken for lab presentation. A very good technique having advantages over conventional KO approaches and allow for the generation of clean CRISPR/ Cas9- based KOs.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
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.
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.
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.
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.
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.
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.
3. Fig. 13-4, p. 283
Nontemplate strand
Transcription
DNA
Template strand
mRNA
(complementary
copy of
template
DNA strand)
Codon 1 Codon 2 Codon 3 Codon 4 Codon 5 Codon 6
Polypeptide Met Thr Cys Glu Cys Phe
Translation
‘
‘
‘
‘
‘
‘
4.
5.
6. Fig. 13-20a, p. 299
Normal DNA sequence
Normal mRNA sequence
Normal
protein
sequence
BASE-SUBSTITUTION
MUTATIONS
Missense
mutation
Nonsense
mutation
(Stop)
(Stop)
(Stop)
7. Fig. 13-20b, p. 299
FRAMESHIFT
MUTATIONS
Normal DNA
sequence
Normal mRNA
sequence
Normal protein
sequence (Stop)
(Stop)
Figure 22.29
Secretory pathway in eukaryotic cells. Proteins whose synthesis begins in the cytosol are transported into the lumen of the endoplasmic reticulum. After further modification in the Golgi apparatus, the proteins are secreted.
Figure 13.4: An overview of transcription and translation.
In transcription, messenger RNA is synthesized as a complementary copy of one of the DNA strands, the template strand. Messenger RNA carries genetic information in the form of sets of three bases, or codons, each of which specifies one amino acid. Codons are translated consecutively, thus specifying the linear sequence of amino acids in the polypeptide chain. Translation requires tRNA and ribosomes (not shown). The figure depicts transcription and translation in bacteria. In eukaryotes, transcription takes place in the nucleus and translation occurs in the cytosol.
Figure 22.17
Shine-Dalgarno sequences in E. coli mRNA. (a) Ribosome-binding sites at the 5' end of mRNA for several E. coli proteins. The Shine-Dalgarno sequences (red) occur immediately upstream of initiation codons (blue). (b) Complementary base pairing between the 3' end of 16S rRNA and the region near the 5' end of an mRNA. Binding of the 3' end of the 16S rRNA to the Shine-Dalgarno sequence helps establish the correct reading frame for translation by positioning the initiation codon at the ribosome’s P site.
Figure 13.20: Mutations.
(a) Missense and nonsense mutations are types of base-substitution mutations. A missense mutation results in a polypeptide of normal length, but with an amino acid substitution. A nonsense mutation results in the production of a truncated (shortened) polypeptide, which is usually not functional.
Figure 13.20: Mutations.
(b) A frameshift mutation results from the deletion (shown) or insertion of one or two bases, causing the base sequence following the mutation to shift to a new reading frame. A frame shift may produce a stop codon downstream of the mutation (which would have the same effect as a nonsense mutation caused by base substitution), or it may produce an entirely new amino acid sequence.
Figure 22.5
Tertiary structure of tRNA. The cloverleaf-shaped molecule shown in Fig. 22.4 actually folds up into this three dimensional shape. The tertiary structure of tRNA results from base pairing between the TC loop and the D loop, and two stacking interactions that (a) align the TC arm with the acceptor arm, and (b) align the D arm with the anticodon arm. For clarity, only the ribose-phosphate backbone is shown here.
Figure 22.8
Base pairing at the wobble position. The tRNAAla molecule with the anticodon IGC can bind to any one of three codons specifying alanine (GCU, GCC, or GCA) because I can pair with U, C, or A. Note that the RNA strand containing the codon and the strand containing the anticodon are antiparallel.
Figure 22.15
Sites for tRNA binding in prokaryotic ribosomes. During protein synthesis, the P site is occupied by the tRNA molecule attached to the growing polypeptide chain, and the A site holds an aminoacyl-tRNA. The growing polypeptide chain passes through the tunnel of the large subunit.
Figure 22.12
Comparison of prokaryotic and eukaryotic ribosomes. Both types of ribosomes consist of two subunits, each of which contains ribosomal RNA and proteins. The large subunit of the prokaryotic ribosome contains two molecules of rRNA: 5S and 23S. The large subunit of almost all eukaryotic ribosomes contains three molecules of rRNA: 5S, 5.8S, and 28S. The sequence of the eukaryotic 5.8S rRNA is similar to the sequence of the 5' end of the prokaryotic 23S rRNA.
Figure 22.17
Shine-Dalgarno sequences in E. coli mRNA. (a) Ribosome-binding sites at the 5' end of mRNA for several E. coli proteins. The Shine-Dalgarno sequences (red) occur immediately upstream of initiation codons (blue). (b) Complementary base pairing between the 3' end of 16S rRNA and the region near the 5' end of an mRNA. Binding of the 3' end of the 16S rRNA to the Shine-Dalgarno sequence helps establish the correct reading frame for translation by positioning the initiation codon at the ribosome’s P site.
Figure 22.32
Translocation of eukaryotic proteins into the lumen of the endoplasmic reticulum.
