The document outlines the complex network of molecular interactions involved in the cellular response to shear stress. It shows calcium channels activating phospholipase C which generates diacylglycerol and IP3, mobilizing calcium and activating protein kinase C. Protein kinase C phosphorylates targets and is inhibited by other kinases and phosphatases. Calcium activates calpain protease which degrades talin and paxillin, affecting focal adhesion complexes and mechanotransduction.
Atherosclerosis is the buildup of plaque in artery walls due to injuries to the endothelial lining. Endothelial cells regulate blood flow through signal transduction and are sensitive to physical forces like shear stress from fluid movement. We developed a systems biology model with over 700 molecular reactions to investigate and predict how endothelial cells respond to shear stress at the molecular level. While our model matched some experimental data, it failed to capture other dynamics, suggesting there are still unknown interactions and responses that need to be incorporated.
Presentation given by Dr. Karthikeyan at Department of Biochemistry, Maulana Azad Medical College.
Addition:
There are certain proteins which are degraded by proteasome without ubiquitin tag. one such example is ornithine decarboxylase - rate limiting enzyme of polyamine synthesis.
Proteolysis, protein degradation and turnoveremicica
This document discusses protein degradation and turnover. It begins by introducing proteolysis, which is the cleavage of peptide bonds by proteases. Limited proteolysis can create new protein products with new functions through posttranslational modification. There are two main types of proteases - exopeptidases that cleave near the ends of proteins, and endopeptidases that cleave internally. Protein degradation involves complete breakdown of proteins into amino acids by multiple cleavages and occurs through two main pathways: lysosomal breakdown in acidic lysosomes using individual proteases, and ubiquitin-dependent breakdown by the proteasome in the cytosol at neutral pH.
This document summarizes different ways that enzyme activity can be regulated in cells, including at the level of production, compartmentation, activation/inhibition, post-translational modification, and localization. It describes constitutive enzymes that are always active and regulated enzymes that are only active under certain conditions. Enzyme activity can be regulated at the level of transcription/translation or after protein synthesis via posttranslational modification. Mechanisms of regulation include feedback inhibition, allosteric regulation of activity based on substrate or product binding, phosphorylation/dephosphorylation, and proteolytic activation.
1) Allosteric enzymes have additional sites called allosteric sites that are distinct from the active site. Binding of an effector molecule to these sites can induce a conformational change in the active site, increasing or decreasing the enzyme's activity.
2) There are two main models that describe allosteric regulation - the concerted model where binding causes simultaneous changes in all subunits, and the sequential model where changes occur sequentially.
3) Allosteric enzymes exhibit sigmoidal kinetics curves rather than traditional hyperbolic curves due to their cooperative binding behavior. Positive allosteric effectors increase enzyme activity while negative effectors decrease it.
The document discusses allosteric regulation of enzymes. Allosteric enzymes can exist in two conformations - an active form which can bind substrate and an inactive form which binds inhibitors. Effectors like substrates or inhibitors binding at allosteric sites can stabilize one form over the other. One example discussed is aspartate transcarbamoylase which regulates pyrimidine synthesis and shows cooperative substrate binding and allosteric regulation by ATP and CTP.
Histone Modification: Acetylation n MethylationSomanna AN
This document discusses histone modifications through acetylation and methylation. It explains that DNA wraps around histone proteins to form nucleosomes. Histone tails can be modified through acetylation and methylation, which are regulated by specific enzyme complexes. These modifications affect chromatin structure and transcription by altering the interaction of histone tails with DNA and recruiting other proteins. The combination of modifications on histone tails is referred to as the "histone code", which is read by protein complexes to influence gene expression.
This document appears to be a map or diagram showing various streets, roads, and landmarks in a town. It includes labels for Hillview Street, Rice Avenue, Middle town Road, and Hampton Avenue. The map also depicts several other unlabeled roads and what seems to be a residential neighborhood layout.
Atherosclerosis is the buildup of plaque in artery walls due to injuries to the endothelial lining. Endothelial cells regulate blood flow through signal transduction and are sensitive to physical forces like shear stress from fluid movement. We developed a systems biology model with over 700 molecular reactions to investigate and predict how endothelial cells respond to shear stress at the molecular level. While our model matched some experimental data, it failed to capture other dynamics, suggesting there are still unknown interactions and responses that need to be incorporated.
Presentation given by Dr. Karthikeyan at Department of Biochemistry, Maulana Azad Medical College.
Addition:
There are certain proteins which are degraded by proteasome without ubiquitin tag. one such example is ornithine decarboxylase - rate limiting enzyme of polyamine synthesis.
Proteolysis, protein degradation and turnoveremicica
This document discusses protein degradation and turnover. It begins by introducing proteolysis, which is the cleavage of peptide bonds by proteases. Limited proteolysis can create new protein products with new functions through posttranslational modification. There are two main types of proteases - exopeptidases that cleave near the ends of proteins, and endopeptidases that cleave internally. Protein degradation involves complete breakdown of proteins into amino acids by multiple cleavages and occurs through two main pathways: lysosomal breakdown in acidic lysosomes using individual proteases, and ubiquitin-dependent breakdown by the proteasome in the cytosol at neutral pH.
This document summarizes different ways that enzyme activity can be regulated in cells, including at the level of production, compartmentation, activation/inhibition, post-translational modification, and localization. It describes constitutive enzymes that are always active and regulated enzymes that are only active under certain conditions. Enzyme activity can be regulated at the level of transcription/translation or after protein synthesis via posttranslational modification. Mechanisms of regulation include feedback inhibition, allosteric regulation of activity based on substrate or product binding, phosphorylation/dephosphorylation, and proteolytic activation.
1) Allosteric enzymes have additional sites called allosteric sites that are distinct from the active site. Binding of an effector molecule to these sites can induce a conformational change in the active site, increasing or decreasing the enzyme's activity.
2) There are two main models that describe allosteric regulation - the concerted model where binding causes simultaneous changes in all subunits, and the sequential model where changes occur sequentially.
3) Allosteric enzymes exhibit sigmoidal kinetics curves rather than traditional hyperbolic curves due to their cooperative binding behavior. Positive allosteric effectors increase enzyme activity while negative effectors decrease it.
The document discusses allosteric regulation of enzymes. Allosteric enzymes can exist in two conformations - an active form which can bind substrate and an inactive form which binds inhibitors. Effectors like substrates or inhibitors binding at allosteric sites can stabilize one form over the other. One example discussed is aspartate transcarbamoylase which regulates pyrimidine synthesis and shows cooperative substrate binding and allosteric regulation by ATP and CTP.
Histone Modification: Acetylation n MethylationSomanna AN
This document discusses histone modifications through acetylation and methylation. It explains that DNA wraps around histone proteins to form nucleosomes. Histone tails can be modified through acetylation and methylation, which are regulated by specific enzyme complexes. These modifications affect chromatin structure and transcription by altering the interaction of histone tails with DNA and recruiting other proteins. The combination of modifications on histone tails is referred to as the "histone code", which is read by protein complexes to influence gene expression.
This document appears to be a map or diagram showing various streets, roads, and landmarks in a town. It includes labels for Hillview Street, Rice Avenue, Middle town Road, and Hampton Avenue. The map also depicts several other unlabeled roads and what seems to be a residential neighborhood layout.
The document contains a musical score titled "Canção de Estar Sozinho" (Song of Being Alone). It is written for a chamber ensemble including flute, clarinet, trumpet, trombone, euphonium, two violins, viola, cello, and piano. The score consists of repeating melancholic musical phrases played across the instruments in a slow and somber manner, expressing the lonely sentiment of the title through the music.
The document contains a musical score titled "Canção de Estar Sozinho" (Song of Being Alone). It is scored for flute, clarinet, trumpet, trombone, euphonium, two violins, viola, cello, and piano. The score contains the musical notation for each instrument part across four pages, depicting a slow, melancholic piece of music in 4/4 time.
The document is a musical score for a trumpet solo titled "Toy Soldier Bugle Boy". It contains 16 measures of music scored for both trumpet and piano. The trumpet part features melodic lines played over arpeggiated accompaniment in the piano. Dynamic markings include mezzo forte and piano.
Groups 2010.09: Free/Open Spectrum (Digital Sustainability)Marcus Dapp
The document discusses the electromagnetic spectrum, including:
1) It outlines the different frequency ranges and their common uses, such as radio, television, wireless communications etc.
2) It notes that the spectrum is considered an "immaterial good" and discusses how it could potentially be better utilized.
3) The overview provides context on the spectrum and sets up discussion on managing use of this shared resource.
This document is a musical score for "Gabriel's Oboe" composed by Ennio Morricone for the film soundtrack of "The Mission". The score is written for string instruments including violin I and II, viola, and violoncello. It provides the musical notation through various symbols indicating tempo, dynamics, and notes to be played by each instrument.
The document compares the topographical differences between Melbourne and other cities that influenced their historical rail development. Melbourne's hilly terrain encouraged the early adoption of trams, diverging from other cities. It hopes that by understanding these historical factors, Melbourne can re-inspire growth of its heavy rail network to better meet changing expectations by 2050.
This document discusses 8 different locations, labeled A through H, but provides no other context or information about these locations. It mentions the place names "Palos Verdes", "Luzville Subdivision", and "Sarmiento" but does not connect them or explain their relationship to each other or to locations A through H.
This document is an advertisement for long term care insurance from MassMutual. It recommends that financial representatives advise their clients to prepare for long term care needs through insurance protection from MassMutual, which has over 154 years of financial strength. The ad stresses MassMutual's dedication to customer choice and quality of life. It urges financial representatives to call or visit MassMutual's website for information on how to build expertise and achieve success through MassMutual's training and quality service.
The document contains musical notation for an orchestral piece. It shows the parts for piccolo, flutes, oboe, English horn, clarinets, bass clarinet, bassoon, contrabassoon, horns, trumpets, trombones, tuba, percussion instruments including gong and cymbals, timpani, harp, and strings including violins, viola, cello, and bass. The parts have rhythmic notation and dynamic markings like mf (mezzo forte) indicating the volume.
The document appears to be musical sheet music containing multiple parts for various instruments including flute, clarinet, trumpet, trombone, euphonium, violin, viola and cello. It contains musical notation such as notes, rhythms, dynamics and other performance instructions for each instrument part across several pages.
The document contains musical notation for an orchestral piece of music. Various instruments are notated on different systems, including flute, clarinet, trumpet, trombone, euphonium, violin, viola, and cello. The notation includes rhythmic patterns, pitches, dynamics, and other musical markings to indicate how the piece should be performed.
Art proposição de diretrizes para produção e normalização de resíduo de const...Petiano Camilo Bin
The document summarizes a heterogenous expert system that provides concise summaries. The system analyzes documents, identifies the key elements and essential information, and expresses this in 3 sentences or less. It does this by breaking down the document into individual facts and relationships, and then reassembling the most important pieces into a coherent short-form summary. The system aims to capture the high-level essence and meaning of the original text in a brief, easy to understand format.
The document is a sheet music for Johann Pachelbel's Canon in D. It contains the musical notation for violin and piano parts over 37 measures. The piece is based on a ground bass, or repeating bassline, and features variations in dynamics from pianissimo to forte. It begins with the violin introducing the canonical theme, which is then repeated and varied throughout by both instruments in a cyclic fashion.
This document discusses a complex network of relationships between various groups and individuals. It maps connections between entities using symbols like nodes and edges. The network appears decentralized and interconnected with many indirect relationships in addition to direct connections. Interpreting the meanings and motivations between the different elements would require more context beyond what is provided in this high-level overview.
This is my one of the implemented project in which I played the over all ownership in Design, Configuration, Integration, Implementation and documentation. Due to security reason naming and IP address in this design are not correct.
This document provides a map of Grid 3. It shows the layout of streets and landmarks within Grid 3, including Well Street, Power Station Way, and East Street. Landmarks such as the town hall are marked on the map to help with navigation around Grid 3.
French Fete de la Musique program, Shanghaisplitworks
The Fête de la Musique is an annual musical event held on June 21st in over 350 cities worldwide. It originated in Paris in 1982 and has since become a beloved French tradition. On the summer solstice, the longest day of the year, musicians of all kinds perform free outdoor concerts to celebrate music with the public. Shanghai is bringing this tradition to the city in 2010 to share with Expo visitors. Over 40 musical groups will perform across the city on June 20th, and events will continue at the French Pavilion on June 21st for France's National Day.
This map shows the proposed community health board boundaries for Nova Scotia. The province is divided into 13 community health boards, with boundaries following municipal and geographical lines. Major cities like Halifax and Dartmouth have their own community health boards, while more rural areas are grouped into larger regional community health boards. The map labels all communities, water features, roads, hospitals and other important landmarks to help identify the new community health board structure for Nova Scotia.
This document provides a map showing the location of Idlewild Park in Ligonier, Pennsylvania along with surrounding roads and neighborhoods within a 3.5 mile radius. The map is labeled with street names and includes distances to certain points of interest. Phase One of the park is highlighted on the map.
The document contains a musical score titled "Canção de Estar Sozinho" (Song of Being Alone). It is written for a chamber ensemble including flute, clarinet, trumpet, trombone, euphonium, two violins, viola, cello, and piano. The score consists of repeating melancholic musical phrases played across the instruments in a slow and somber manner, expressing the lonely sentiment of the title through the music.
The document contains a musical score titled "Canção de Estar Sozinho" (Song of Being Alone). It is scored for flute, clarinet, trumpet, trombone, euphonium, two violins, viola, cello, and piano. The score contains the musical notation for each instrument part across four pages, depicting a slow, melancholic piece of music in 4/4 time.
The document is a musical score for a trumpet solo titled "Toy Soldier Bugle Boy". It contains 16 measures of music scored for both trumpet and piano. The trumpet part features melodic lines played over arpeggiated accompaniment in the piano. Dynamic markings include mezzo forte and piano.
Groups 2010.09: Free/Open Spectrum (Digital Sustainability)Marcus Dapp
The document discusses the electromagnetic spectrum, including:
1) It outlines the different frequency ranges and their common uses, such as radio, television, wireless communications etc.
2) It notes that the spectrum is considered an "immaterial good" and discusses how it could potentially be better utilized.
3) The overview provides context on the spectrum and sets up discussion on managing use of this shared resource.
This document is a musical score for "Gabriel's Oboe" composed by Ennio Morricone for the film soundtrack of "The Mission". The score is written for string instruments including violin I and II, viola, and violoncello. It provides the musical notation through various symbols indicating tempo, dynamics, and notes to be played by each instrument.
The document compares the topographical differences between Melbourne and other cities that influenced their historical rail development. Melbourne's hilly terrain encouraged the early adoption of trams, diverging from other cities. It hopes that by understanding these historical factors, Melbourne can re-inspire growth of its heavy rail network to better meet changing expectations by 2050.
This document discusses 8 different locations, labeled A through H, but provides no other context or information about these locations. It mentions the place names "Palos Verdes", "Luzville Subdivision", and "Sarmiento" but does not connect them or explain their relationship to each other or to locations A through H.
This document is an advertisement for long term care insurance from MassMutual. It recommends that financial representatives advise their clients to prepare for long term care needs through insurance protection from MassMutual, which has over 154 years of financial strength. The ad stresses MassMutual's dedication to customer choice and quality of life. It urges financial representatives to call or visit MassMutual's website for information on how to build expertise and achieve success through MassMutual's training and quality service.
The document contains musical notation for an orchestral piece. It shows the parts for piccolo, flutes, oboe, English horn, clarinets, bass clarinet, bassoon, contrabassoon, horns, trumpets, trombones, tuba, percussion instruments including gong and cymbals, timpani, harp, and strings including violins, viola, cello, and bass. The parts have rhythmic notation and dynamic markings like mf (mezzo forte) indicating the volume.
The document appears to be musical sheet music containing multiple parts for various instruments including flute, clarinet, trumpet, trombone, euphonium, violin, viola and cello. It contains musical notation such as notes, rhythms, dynamics and other performance instructions for each instrument part across several pages.
The document contains musical notation for an orchestral piece of music. Various instruments are notated on different systems, including flute, clarinet, trumpet, trombone, euphonium, violin, viola, and cello. The notation includes rhythmic patterns, pitches, dynamics, and other musical markings to indicate how the piece should be performed.
Art proposição de diretrizes para produção e normalização de resíduo de const...Petiano Camilo Bin
The document summarizes a heterogenous expert system that provides concise summaries. The system analyzes documents, identifies the key elements and essential information, and expresses this in 3 sentences or less. It does this by breaking down the document into individual facts and relationships, and then reassembling the most important pieces into a coherent short-form summary. The system aims to capture the high-level essence and meaning of the original text in a brief, easy to understand format.
The document is a sheet music for Johann Pachelbel's Canon in D. It contains the musical notation for violin and piano parts over 37 measures. The piece is based on a ground bass, or repeating bassline, and features variations in dynamics from pianissimo to forte. It begins with the violin introducing the canonical theme, which is then repeated and varied throughout by both instruments in a cyclic fashion.
This document discusses a complex network of relationships between various groups and individuals. It maps connections between entities using symbols like nodes and edges. The network appears decentralized and interconnected with many indirect relationships in addition to direct connections. Interpreting the meanings and motivations between the different elements would require more context beyond what is provided in this high-level overview.
This is my one of the implemented project in which I played the over all ownership in Design, Configuration, Integration, Implementation and documentation. Due to security reason naming and IP address in this design are not correct.
This document provides a map of Grid 3. It shows the layout of streets and landmarks within Grid 3, including Well Street, Power Station Way, and East Street. Landmarks such as the town hall are marked on the map to help with navigation around Grid 3.
French Fete de la Musique program, Shanghaisplitworks
The Fête de la Musique is an annual musical event held on June 21st in over 350 cities worldwide. It originated in Paris in 1982 and has since become a beloved French tradition. On the summer solstice, the longest day of the year, musicians of all kinds perform free outdoor concerts to celebrate music with the public. Shanghai is bringing this tradition to the city in 2010 to share with Expo visitors. Over 40 musical groups will perform across the city on June 20th, and events will continue at the French Pavilion on June 21st for France's National Day.
This map shows the proposed community health board boundaries for Nova Scotia. The province is divided into 13 community health boards, with boundaries following municipal and geographical lines. Major cities like Halifax and Dartmouth have their own community health boards, while more rural areas are grouped into larger regional community health boards. The map labels all communities, water features, roads, hospitals and other important landmarks to help identify the new community health board structure for Nova Scotia.
This document provides a map showing the location of Idlewild Park in Ligonier, Pennsylvania along with surrounding roads and neighborhoods within a 3.5 mile radius. The map is labeled with street names and includes distances to certain points of interest. Phase One of the park is highlighted on the map.
This thesis examines how endothelial cells respond and polarize in response to fluid flow through three-dimensional modelling and simulations. It first reviews prior models of cytoskeleton dynamics and mechanics. It then presents a Brownian dynamics model of actin polymerization during lamellipodium formation. A boundary integral representation is used to model fluid flow over a single cell. A Kelvin-body model couples this flow to a PDE model of Rho GTPase activity to understand mechanotransduction and signal transduction dynamics during endothelial cell polarization and elongation in response to fluid flow. Validation against experimental data on Rho GTPase activation time courses is also discussed.
This document provides a summary of Konstantinos Lykostratis's professional experience and qualifications. It outlines his experience as a project manager and systems biology researcher, including his roles developing software solutions and mathematical models. It also lists his educational background, obtaining a PhD in computational systems biology and bioinformatics from University College London, and a BSc in human genetics from the University of Leicester.
1. The document discusses systems biology approaches to modeling the endothelial cell response to fluid shear stress. It describes experimental techniques to apply controlled fluid shear stress and measure downstream cellular responses.
2. Mathematical models are formulated to represent molecular interactions and pathways involved in the shear stress response. Model predictions are compared to experimental data to validate and refine the models.
3. The models can provide insights into critical components, feedback loops, and how external perturbations may influence the cellular response to shear stress. Further experimental validation of model predictions is needed.
This PhD thesis presents a mathematical model of the signalling pathways regulating endothelial cell responses to fluid shear stress. The model consists of 8 interconnected modules describing processes such as calcium dynamics, calpain activity, integrin activation, and the phosphorylation of proteins like FAK and Src. Differential equations are used to simulate the dynamic behaviour of molecular species over time under varying shear stress conditions. The model aims to improve understanding of how fluid flow stimulation is converted into biochemical signals in endothelial cells and how this relates to the development of atherosclerosis.
1. K.Lykostratis Fn
Shear Stress response L
Shear Stress
Calcium Fn
channel Fn
L
PIP2 PLC G Ra R
Fn
+ qin TalinIn Talin Talin Talin
+/- t
Calpain Paxillin
Calpain TalinIn Ta
t Talin lin
degradation a
Paxillin
*
a
Na+ -Ca+ DAG Pa
exchanger TalinCl xilli FA
n K i
v
Calpain Calpastatin FAKi
IP3 RPTP i
Talin
Cac PKC-Ca- a RPTP
qex GRB2
Paxillin
a
Fn
PKCa Calpain PIPKIγ661 Paxillin
PKC-Ca
* Paxillin*
PKCbas
FAKi
Calpastatin
a Talin FAKi
GRB2
+ PKCi *
RPTP PIPKIγ661 PIPKIγ661 FAK
R
aP *
Talin
qcc
Cas IKKi
Paxillin*
Capacitative IKKi PKCa
Fn
calcium entry *
SRCi-p SRC SRC FAK
Ca2+ qres - ER
-ATPase
IKKa
PTP_3 Paxillin*
Talin
PTP_P
Paxillin
CSK
EST *
FAK
*
LEGEND
Ik NF-kB NF-kB
Fn
= Affinity
FAK
= Catalysis
*
= Nuclear ERKp
= Enzyme ERKpp
PTP_PE
nucleus
ST
= GTPase GEF NF-kB
Talin
IkBαt ERK
Paxillin
= GTPase
*
IkBβt
= Adaptor Ik NF-kB PTP_2
IkBεt C-fos
Fn
ES _P FAK
= Phosphatase C-jun
T
P
*
PT
= Kinase
Ik
= TF MEKpp
B Ik Ik Ik MEK Paxillin**
B B B
MEKp
RasG
Paxillin*
Talin
TPp
GRB2
SOS
Paxillin
RasG * SRC
*
FAK
FAK
TPp RasG
PTP_PE **
**
Fn
FAK
TP FAK
Fn
Paxillin
ST
SRC
**
*
RAF RAFp
Talin
RasG
DP RasG
TP
* *
SRC SRC
Talin
RasG
GRB2
SOS
DP
RAF
PTP_1
Paxillin*
FAK
PTP_SR
*
Fn
*
**
C FAK SRC
Fn
Paxillin
**
Talin
SOS
SOS
DOCK1 Paxillin**
GRB2
CRK ** Talin Fn
FAK
GRB2
SOS
FAK
**
Fn
Paxillin
**
DOCK1
CAS
Talin
CRK
Talin
Paxill
*
GR
in FAK
B2
Pa
FA xil
*
K ** ** li n DOCK1 DOCK1 DOCK1
Fn
DOCK1
Ta CRK CRK CRK
li CRK CRK CRK n
n CRK CAS Paxillin Paxillin Pax*illi
Paxillin Paxillin CAS* Paxillin CAS* Paxillin CAS* Paxillin CAS* Paxillin *
SRC Talin
** **
**
** CAS Paxillin ** ** **
**
** Talin Talin ** Talin *
** Talin ** Talin **
** Talin ** Talin ** Talin ** Talin FAK FAK FAK
FAK FAK FAK FAK FAK FAK
FAK
** Talin
Fn
Fn Fn Fn Fn Fn Fn
Fn Fn Fn Fn
Fn
1