An overview of the history of structural studies of G protein-coupled receptors, written by Prof. Tony Harmar prior to his retirement from the University of Edinburgh and as chair of the Guide to PHARMACOLOGY.
Replication Introduction , DNA replicating Models , Meselson and Stahl Experiments , Circuler Model of DNA replication , Replication in Prokaryotes , Replication In Eukaryotes , Comparison Between Prokaryotes and Eukaryotes Replicaton and PCR (Polymerease Chain Reaction)
An overview of the history of structural studies of G protein-coupled receptors, written by Prof. Tony Harmar prior to his retirement from the University of Edinburgh and as chair of the Guide to PHARMACOLOGY.
Replication Introduction , DNA replicating Models , Meselson and Stahl Experiments , Circuler Model of DNA replication , Replication in Prokaryotes , Replication In Eukaryotes , Comparison Between Prokaryotes and Eukaryotes Replicaton and PCR (Polymerease Chain Reaction)
DNA organization or Genetic makeup in Prokaryotic and Eukaryotic SystemsBir Bahadur Thapa
DNA organization or Genetic makeup in Prokaryotic and Eukaryotic Systems!! It is prepared under the syllabus of Tribhuwan University, Nepal, MSc. 3rd Semester as a lecture class!!
Plasmid is a double stranded, circular extra chromosomal DNA of bacterium. It is used in recombinant DNA experiments to clone genes from other organisms and make large quantities of their DNA. Plasmid can be transferred between same species or between different species. Size of plasmids range from 1-1000 kilo base pairs. Plasmids are part of mobilomes (total of all mobile genetic elements in a genome) like transposons or prophages and are associated with conjugation. Even the largest plasmids are considerably smaller than the chromosomal DNA of the bacterium, which can contain several million base pairs.
A blot, in molecular biology and genetics, is a method of transferring proteins, DNA or RNA, onto a carrier (for example, a nitrocellulose, polyvinylidene fluoride (PVDF) or nylon membrane). In many instances, this is done after a gel electrophoresis, transferring the molecules from the gel onto the blotting membrane, and other times adding the samples directly onto the membrane. After the blotting, the transferred proteins, DNA or RNA are then visualized by colorant staining (for example, silver staining of proteins), autoradiographic visualization of radioactive labelled molecules (performed before the blot), or specific labelling of some proteins or nucleic acids. The latter is done with antibodies or hybridization probes that bind only to some molecules of the blot and have an enzyme joined to them. After proper washing, this enzymatic activity (and so, the molecules we search in the blot) is visualized by incubation with proper reactive, rendering either a colored deposit on the blot or a chemiluminiscent reaction which is registered by photographic film.
Southern blot
A Southern blot is a method routinely used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detection by probe hybridization.[1]
Western blot
A Western blot is used for the detection of specific proteins in complex samples. Proteins are first separated by size using electrophoresis before being transferred to an appropriate blotting matrix (usually PVDF or nitrocellulose) and subsequent detection with antibodies.
Eastern blot
The Eastern blot is used for the detection of specific posttranslational modifications of proteins. Proteins are separated by gel electrophoresis before being transferred to a blotting matrix whereupon posttranslational modifications are detected by specific substrates (cholera toxin, concanavalin, phosphomolybdate, etc.) or antibodies.
DNA replication, repair and recombination NotesYi Fan Chen
DNA, replication, repair and recombination Notes based on Molecular biology of the cell. Biology Elite: biologyelite.weebly.com, please use together with the presentation
Microbial genetics is a subject area within microbiology and genetic engineering. This involves the study of the genotype of microbial species and also the expression system in the form of phenotypes
DNA organization or Genetic makeup in Prokaryotic and Eukaryotic SystemsBir Bahadur Thapa
DNA organization or Genetic makeup in Prokaryotic and Eukaryotic Systems!! It is prepared under the syllabus of Tribhuwan University, Nepal, MSc. 3rd Semester as a lecture class!!
Plasmid is a double stranded, circular extra chromosomal DNA of bacterium. It is used in recombinant DNA experiments to clone genes from other organisms and make large quantities of their DNA. Plasmid can be transferred between same species or between different species. Size of plasmids range from 1-1000 kilo base pairs. Plasmids are part of mobilomes (total of all mobile genetic elements in a genome) like transposons or prophages and are associated with conjugation. Even the largest plasmids are considerably smaller than the chromosomal DNA of the bacterium, which can contain several million base pairs.
A blot, in molecular biology and genetics, is a method of transferring proteins, DNA or RNA, onto a carrier (for example, a nitrocellulose, polyvinylidene fluoride (PVDF) or nylon membrane). In many instances, this is done after a gel electrophoresis, transferring the molecules from the gel onto the blotting membrane, and other times adding the samples directly onto the membrane. After the blotting, the transferred proteins, DNA or RNA are then visualized by colorant staining (for example, silver staining of proteins), autoradiographic visualization of radioactive labelled molecules (performed before the blot), or specific labelling of some proteins or nucleic acids. The latter is done with antibodies or hybridization probes that bind only to some molecules of the blot and have an enzyme joined to them. After proper washing, this enzymatic activity (and so, the molecules we search in the blot) is visualized by incubation with proper reactive, rendering either a colored deposit on the blot or a chemiluminiscent reaction which is registered by photographic film.
Southern blot
A Southern blot is a method routinely used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detection by probe hybridization.[1]
Western blot
A Western blot is used for the detection of specific proteins in complex samples. Proteins are first separated by size using electrophoresis before being transferred to an appropriate blotting matrix (usually PVDF or nitrocellulose) and subsequent detection with antibodies.
Eastern blot
The Eastern blot is used for the detection of specific posttranslational modifications of proteins. Proteins are separated by gel electrophoresis before being transferred to a blotting matrix whereupon posttranslational modifications are detected by specific substrates (cholera toxin, concanavalin, phosphomolybdate, etc.) or antibodies.
DNA replication, repair and recombination NotesYi Fan Chen
DNA, replication, repair and recombination Notes based on Molecular biology of the cell. Biology Elite: biologyelite.weebly.com, please use together with the presentation
Microbial genetics is a subject area within microbiology and genetic engineering. This involves the study of the genotype of microbial species and also the expression system in the form of phenotypes
Effects of modifying backbone flexibility in α3 subunits of nicotinic acetylc...Victoria Dorich
A summary of my undergraduate research conducted in the Wells Lab my junior year presented at the 2013 Biochemistry and Genetics Society Poster Session.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
Speakers:
👨🏫 Andras Palfi, Senior Product Manager, UiPath
👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
Securing your Kubernetes cluster_ a step-by-step guide to success !KatiaHIMEUR1
Today, after several years of existence, an extremely active community and an ultra-dynamic ecosystem, Kubernetes has established itself as the de facto standard in container orchestration. Thanks to a wide range of managed services, it has never been so easy to set up a ready-to-use Kubernetes cluster.
However, this ease of use means that the subject of security in Kubernetes is often left for later, or even neglected. This exposes companies to significant risks.
In this talk, I'll show you step-by-step how to secure your Kubernetes cluster for greater peace of mind and reliability.
Le nuove frontiere dell'AI nell'RPA con UiPath Autopilot™UiPathCommunity
In questo evento online gratuito, organizzato dalla Community Italiana di UiPath, potrai esplorare le nuove funzionalità di Autopilot, il tool che integra l'Intelligenza Artificiale nei processi di sviluppo e utilizzo delle Automazioni.
📕 Vedremo insieme alcuni esempi dell'utilizzo di Autopilot in diversi tool della Suite UiPath:
Autopilot per Studio Web
Autopilot per Studio
Autopilot per Apps
Clipboard AI
GenAI applicata alla Document Understanding
👨🏫👨💻 Speakers:
Stefano Negro, UiPath MVPx3, RPA Tech Lead @ BSP Consultant
Flavio Martinelli, UiPath MVP 2023, Technical Account Manager @UiPath
Andrei Tasca, RPA Solutions Team Lead @NTT Data
DevOps and Testing slides at DASA ConnectKari Kakkonen
My and Rik Marselis slides at 30.5.2024 DASA Connect conference. We discuss about what is testing, then what is agile testing and finally what is Testing in DevOps. Finally we had lovely workshop with the participants trying to find out different ways to think about quality and testing in different parts of the DevOps infinity loop.
PHP Frameworks: I want to break free (IPC Berlin 2024)Ralf Eggert
In this presentation, we examine the challenges and limitations of relying too heavily on PHP frameworks in web development. We discuss the history of PHP and its frameworks to understand how this dependence has evolved. The focus will be on providing concrete tips and strategies to reduce reliance on these frameworks, based on real-world examples and practical considerations. The goal is to equip developers with the skills and knowledge to create more flexible and future-proof web applications. We'll explore the importance of maintaining autonomy in a rapidly changing tech landscape and how to make informed decisions in PHP development.
This talk is aimed at encouraging a more independent approach to using PHP frameworks, moving towards a more flexible and future-proof approach to PHP development.
Builder.ai Founder Sachin Dev Duggal's Strategic Approach to Create an Innova...Ramesh Iyer
In today's fast-changing business world, Companies that adapt and embrace new ideas often need help to keep up with the competition. However, fostering a culture of innovation takes much work. It takes vision, leadership and willingness to take risks in the right proportion. Sachin Dev Duggal, co-founder of Builder.ai, has perfected the art of this balance, creating a company culture where creativity and growth are nurtured at each stage.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
2. Structure of the first membrane
protein
The first membrane protein that was structurally characterised, by RichardHenderson
(left) and Nigel Unwin (right) in 1975, was bacteriorhodopsin, a light-harvesting
membrane protein from the archaean Halobacterium halobium that acts as a lightdriven proton pump and is the only protein constituent of the purple membrane, a
two-dimensional crystal lattice naturally present as part of the plasma membrane of
the bacterium.
3. Bacteriorhodopsin -the first 7TM protein
Using electron diffraction, Henderson
& Unwin showed that the protein
contains seven alpha-helices that
enclose
an
all-trans retinal
chromophore
that undergoes an
isomerisation process upon light
absorption that results in the
translocation of a proton from the
cytoplasmic side to the extracellular
side
of
the
membrane.They
commented, almost prophetically“The
purple membrane thus seems to provide
a simple example of an 'intrinsic'
membrane protein, a class of structure
to which many molecular pumps and
channels must belong. We would not be
surprised if the simple arrangement of
helices found here also occurs in some of
these other intrinsic membrane proteins”
4. Amino acid sequence of bacteriorhodopsin
The amino acid sequence of bacteriorhodopsin was first published, almost
simultaneously, by the groups of Yuri Ovchinnikov in 1978 and Nobel Laureate Har
Gobind Khorana in1979. Each study represented a tour de force of protein
chemistry.
5. The first depiction of the 7TM topology of bacteriorhodopsin, from Ovchinnikov.
6. Amino acid sequence of the first GPCR
1983: Complete amino acid sequence of bovine rhodopsin
determined by the laboratories of Ovchinnikov (Russia) and
Hargrave (USA.
7. First cDNA and gene sequences
1983:cloning of cDNA and gene encoding bovine rhodopsin by Jeremy Nathans (left)
and David Hogness (right). Using a “citation classic” technique for homology
screening devised by Hogness, they later identified three related visual pigment
10. Cloning the β 2 adrenoceptor
•
Receptor from hamster lung solubilised in detergent and purified by
affinity chromatography on alprenolol-sepharose
•
Progress of purification monitored by binding of [ 125 I]-cyanopindolol
•
Attempts to obtain amino acid sequence of the intact protein failed
•
Purified protein was subjected to chemical cleavage with cyanogen
bromide (CNBr), which cleaves proteins after every methionine
residue
•
Cyanogen bromide fragments were purified by HPLC and
sequenced
13. 1988:the first "orphan" GPCR
Nature 335: 358-360 (1988)
G-21 was a genomic clone with homology to the β2AR: at
first its endogenous ligand was unknown, i.e. it encoded
an “orphan” GPCR
Nature 335: 358-360 (1988)
14. 1988:5-HT1A receptor “deorphanised”
When expressed in cell lines and studied in a radioligand
binding assay, G-21 exhibited the pharmacology of the 5HT1A receptor
15. 1987:Expression cloning of the NK2 receptor,
the first peptide GPCR
1987:cDNA sequence encoding the the NK2 receptor was
reported by the group of Shigetada Nakanishi using an
ingenious expression cloning strategy
16. Cloning the NK 2 receptor by expression in
Xenopus oocytes
1987:pools of mRNA transcripts from bovine stomach cDNAwere injected
into Xenopus oocytes and tested for electrophysiological responses to
neurokinin A. Pools were progressively subdivided until a single responsive
17. 1991:Expression cloning of the metabotropic
glutamate receptor mGlu1, the first GPCR from
Class C
1991:The cDNA sequence was also cloned by Nakanishi’s group via
screening of RNA transcripts in Xenopus oocytes. Picture shows
mRNA distribution in hippocampus by in situ hybridisation
18. 1991:Expression cloning of the secretin receptor,
the first Class B GPCR
1991:The secretin receptor was cloned by the laboratory of
Shigekazu Nagata by expression in COS cells
19. 1991:Crystal structure of rhodopsin
1991:Crystal structure of rhodopsin determined by Krzysztof Palczewski and
colleagues (click to play movie)
21. 2007:Crystal structure of the β2 adrenoceptor
2007:the first high-resolution structure of a GPCR. Crystal structure was determined by the labs of
Brian Kobilka and Ray Stevens. Science cover caption reads”Structure of the human β2-adrenergic
receptor (red) embedded in a lipid membrane and bound to a diffusible ligand (green), with
cholesterol (yellow) between the two receptor molecules. A cartoon of the lipidic cubic phase used
for crystallization of the receptor is shown in the background”
22. Activated human β2 adrenergic receptor (in blue ) in a complex with a
heterotrimeric G protein (3 subunits:reddish to orange-brown) and
hormone (gold), resolution 3.2Å. The boundaries of the membrane in
which the GPCR sits are represented in light green. From Proteopedia
(click to play movie).
23. Activated human β2 adrenergic receptor (in blue ) in a complex with a
heterotrimeric G protein (3 subunits:reddish to orange-brown) and
hormone (gold), resolution 3.2Å. The boundaries of the membrane in
which the GPCR sits are represented in light green. From Proteopedia
(click to play movie).
24. 2012:Nobel Prize in Chemistry
Awarded to Robert Lefkowitz (left)and Brian Kobilka (right) "for studies of
G-protein-coupled receptors"