G-protein coupled receptors (GPCRs) are the largest family of membrane receptors that are linked to intracellular effector proteins via G-protein activation. There are several classes of GPCRs classified based on sequence homology. All GPCRs have seven transmembrane domains and signal through heterotrimeric G proteins. When a ligand binds a GPCR, it activates an associated G protein which then regulates downstream effectors like adenylyl cyclase or phospholipase C. These pathways mediate many physiological processes such as vision, smell, immune response, and neuronal signaling.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Cell Signalling Pathway (intra and extra cellular signalling)Aneela Rafiq
the way of communication cell to cell or cell to their environment. they produce some stimuli to correspond to surroundings for survival. Cell signalling helps to defend, survive, production of chemicals and lots of other things. signalling can external and internal. in this presentation, paths are elaborated externally and internally.
Hope it will help to understand cell signal in better way.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Cell Signalling Pathway (intra and extra cellular signalling)Aneela Rafiq
the way of communication cell to cell or cell to their environment. they produce some stimuli to correspond to surroundings for survival. Cell signalling helps to defend, survive, production of chemicals and lots of other things. signalling can external and internal. in this presentation, paths are elaborated externally and internally.
Hope it will help to understand cell signal in better way.
Receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased agonism
Cell signaling / Signal Transduction / Transmembrane signaling.
It is the process by which cells communicate with their environment and respond to external stimuli.
When a signaling molecule(ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell such as alteration in the activity of a gene / cell division. Thus the original Intercellular Signal is converted into an Intracellular Signal that triggers as a response.
Receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased agonism
Cell signaling / Signal Transduction / Transmembrane signaling.
It is the process by which cells communicate with their environment and respond to external stimuli.
When a signaling molecule(ligand) binds to its receptor, it alters the shape or activity of the receptor, triggering a change inside of the cell such as alteration in the activity of a gene / cell division. Thus the original Intercellular Signal is converted into an Intracellular Signal that triggers as a response.
Signal transducing machinery as targets for potential drugs.
Drugs:-
a). Diclofenac- for treating cholera toxin
b). Fasentin- for treating insulin signalling
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
3. G-protein Coupled Receptors (GPCRS) are the
largest and more diverse group of
membrane receptors in eukaryotes .
There are large family of cell membrane
receptors which are linked to the effector
through one/more G-T-P activated for
response effectuation.
4. In 2012, Robert lef kowitz and brian kobilka
won the nobel prize in chemistry for
ground breaking discoveries that reveal
the inner workings of an important
family of G-protein coupled receptors .
5. Based on sequence homology and
functional similarity….
ClassA(or)1-Rhodopsin like receptors
ClassB(or)2-secretin family
ClassC(or)3-metabotropic glutamate
receptors
ClassD(or)4-fungal mating phermone
receptors
ClassE(or)5-cyclic AMP receptors
ClassF(or)6-frizzled and smoothened
receptors
6. Based on phylogenetic origin the G-protein
coupled receptor classification system has
been proposed as :
1.Glutamates
2.Rhodopsin
3.Adhesion
4.Frizzled/Taste
5.secretin
7. All receptors hve a common pattern of
structural organisation.
Molecule has 1α-helical membrane
spanning hydrophobic aminoacid segments
which run into 3 entracellular and 3
intracellular loops .
8.
9. The agonist binding site is located somewhich
between on the entracellular face ; which
another recognization site formed by cytosolic
segments binds the coupling G-protein .
The G-protein float in the membrane with there
exposed domain lying in the cytosol and are
heterotrimeric in composition of α,ß and Γ sub
units .
In the inactive state GDP is bound to the α sub
unit at the exposed domain activation through
the receptor leads to displacement of GDP by
GTP .
10. The activated α-sub unit carrying GTP
dissociates from the other two subunits and
either activates or inhibits the effector .
The ßΓ (beta,gamma) dimer has also been
shown to active receptor-operated K+
channels, to inhibit volated gated Ca2+
channels and to promote GPCR(G-protein
coupled receptors) descmitization at higher
rate of activation
11. A number of G proteins distinguished by the
α-sub units has been describes the important
ones with their action on the effector are
Gs: Adenylyl cyclase activation,ca+2 channel
Gi: Adenylyl cclase inhibition,K+channel
Go:Ca2+ channel inhibitor
Gq:phospholipase c activation
12.
13. The adenylyl cyclase increase CAMP pathway
• CAMP is a nucleotide
• Synthesized with in the cell from ATP by
membrane bound adenylyl cyclase.
• Produced continously .
• Inactivated by hydrolysis to 5′-AMP,by the
phospho diesterase.
• Common mechanisms , namely the
activation of protein kinase .
14. Involved in :-
Energy metabolism
Cell division and differentiation
Ion transport , ion channels
Contractile proteins in smooth muscle
15.
16.
17. Phospholipases c:- IP3-DAG pathway:-
• Activation of phospholipase Cß(PLCß) by
the activated GTP carrying α subunit of Gq
hydrolyses.the membrane phospholipids
phosphotidyl ionsitol4,5-bis
phosphate(PIP2) to generate the second
messengers inositol 1,4,5-triphosphate(IP3)
and diacylglycerol(DAG).
• The IP3 being water soluble diffuses to the
cytosol and mobilizer ca+2 from
endoplasmic reticulum depots .
18. But the lipophilic DAG remains within the membrane
but recruits protein kinase C.
Activates it with the help of ca+2
The activated PKc phosphorylates many intracellular
proteins(depending on the type of effector cells and
mediates various physiological responses).
So that it can serve signalling functions,the cytosolic
concentrations of ca+2 is kept very low(≈100nm) by
specific pumps located at the plasma membrane and
at the endoplasmic reticulum.
Triggered by IP3, the released ca+2 acts on a highly
versatile regulator acting through
calmodulin(CAM),Pkcand other effectirs .
19.
20. The activated G-proteins (Gs,Gi,Go) can
also open or inhibit ionic channels specific
for ca2+ and k+, without the intervention
of any second messengers like cAMP or IP3.
The bring about
hyperpolarization/depolarization changes
in intracellular ca+2 concentrations.
The Gs opens ca2+ channels in myocardium
and skeletal muscles, which Gi and Go open
k+ channels in heart ans smooth muscles
as well as inhibit neuronal ca2+ channels .
21. Direct channel regulation is mostly the
functions of the ß^ dimer of the dissociated
Gprotein physiological responses like
changes in inotopy , chronotropy ,
transmitter release, neuronal activity and
smooth muscle relaxation follow.
Receptors found to regulate ionic channels
through G-proteins.
22. • Visual sense
• taste and smell
• Behavioural and mood regulation
• Immune system activity and inflammation
• Ans transmission
• Apoptosis
23. GPCRS are a large family of cell surface that
respond to a variety of external signals.
Binding of a signaling molecule to a GPCR
results in G protein activation, which in turn
triggers the production of any number of
second messengers
24. Essentials of medical pharmacology by KD
Tripathi…
https://www.nature.com>topicpage.
