This study identified protein interaction partners of protein phosphatase 2A catalytic subunit (PP2Ac) in rat pancreatic β-islet cells under low and high glucose conditions using quantitative mass spectrometry. 514 total PP2Ac interaction partners were found, with 89 showing a significant difference between low and high glucose. Of these, 265 had over 1.5-fold change between the two conditions. Pathway analysis revealed 59 significantly enriched pathways among the partners, including insulin secretion, vesicle trafficking, protein degradation and transcription control. This provides the largest PP2Ac interaction network in rat β-cells to date and partners involved in key functions like insulin secretion.
Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Mode...Sean Ekins
Slides from SERMACS 2015 meeting in Memphis 2015 describing a collaborative project with SRI International and Rutgers. The work was published in PLOS ONE http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141076
The three hybrid system of yeast has been described in this ppt. Yeast one Hybrid system, yeast two hybrid system and yeast 3 hybrid system is explained. This explain about the DNA-protein interaction and Protein-DNA-Protein interaction.
Antibody Directed Enzyme Prodrug therapy is a technique of active drug targeting therapy which was developed to reduce cancer chemotherapy associated Toxicity
AXL kinase is a receptor tyrosine kinase which works using signal cascade mechanism and has essential use in anticancer activity of some drugs having AXL inhibition as thein mechanism of action
dkNET Webinar: The Mouse Metabolic Phenotyping Centers: Services and Data 01/...dkNET
The Mouse Metabolic Phenotyping Centers (MMPC) is a National Institutes of Health-Sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice. Dr. Richard McIndoe will introduce resources and tools that are available at MMPC.
Abstract
A common strategy to dissect the etiology, genetics and underlying physiology of a disease is to create mouse models using gene targeting and manipulation techniques. These mouse models were developed by targeting one or more candidate genes or by using a whole genome mutagenesis strategy. The careful and reproducible characterization of these animal models is important for the advancement of biomedical research. The expense, expertise and time required to develop state-of-the-art phenotyping technologies is beyond the reach of many investigators. The Mouse Metabolic Phenotyping Centers (MMPC) were created to provide the scientific community with cost effective, high quality, standardized metabolic and phenotyping services. The focus of the MMPC is on experiments that characterize living animals as well as providing technologies that are important for understanding metabolism and physiology. The MMPC provides state-of-the-art technologies to investigators for a fee, with their services including characterization of mouse metabolism, blood composition (including hormones), energy balance, eating and exercise, organ function and morphology, physiology and histology. There are currently five MMPC Centers located at Vanderbilt University, University of California Davis, University of Cincinnati, University of Massachusetts and the University of Michigan. Investigators using the MMPC services agree to release the data generated by the MMPC to the general public via the national website database. This talk will review the structure of the MMPC, the services it provides and the data generated by the consortium for public use.
Presenter: Dr. Richard McIndoe, Professor, College of Graduate Studies and the College of Allied Health Sciences, Medical College of Georgia.
More information: https://dknet.org/about/webinar
Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Mode...Sean Ekins
Slides from SERMACS 2015 meeting in Memphis 2015 describing a collaborative project with SRI International and Rutgers. The work was published in PLOS ONE http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141076
The three hybrid system of yeast has been described in this ppt. Yeast one Hybrid system, yeast two hybrid system and yeast 3 hybrid system is explained. This explain about the DNA-protein interaction and Protein-DNA-Protein interaction.
Antibody Directed Enzyme Prodrug therapy is a technique of active drug targeting therapy which was developed to reduce cancer chemotherapy associated Toxicity
AXL kinase is a receptor tyrosine kinase which works using signal cascade mechanism and has essential use in anticancer activity of some drugs having AXL inhibition as thein mechanism of action
dkNET Webinar: The Mouse Metabolic Phenotyping Centers: Services and Data 01/...dkNET
The Mouse Metabolic Phenotyping Centers (MMPC) is a National Institutes of Health-Sponsored resource that provides experimental testing services to scientists studying diabetes, obesity, diabetic complications, and other metabolic diseases in mice. Dr. Richard McIndoe will introduce resources and tools that are available at MMPC.
Abstract
A common strategy to dissect the etiology, genetics and underlying physiology of a disease is to create mouse models using gene targeting and manipulation techniques. These mouse models were developed by targeting one or more candidate genes or by using a whole genome mutagenesis strategy. The careful and reproducible characterization of these animal models is important for the advancement of biomedical research. The expense, expertise and time required to develop state-of-the-art phenotyping technologies is beyond the reach of many investigators. The Mouse Metabolic Phenotyping Centers (MMPC) were created to provide the scientific community with cost effective, high quality, standardized metabolic and phenotyping services. The focus of the MMPC is on experiments that characterize living animals as well as providing technologies that are important for understanding metabolism and physiology. The MMPC provides state-of-the-art technologies to investigators for a fee, with their services including characterization of mouse metabolism, blood composition (including hormones), energy balance, eating and exercise, organ function and morphology, physiology and histology. There are currently five MMPC Centers located at Vanderbilt University, University of California Davis, University of Cincinnati, University of Massachusetts and the University of Michigan. Investigators using the MMPC services agree to release the data generated by the MMPC to the general public via the national website database. This talk will review the structure of the MMPC, the services it provides and the data generated by the consortium for public use.
Presenter: Dr. Richard McIndoe, Professor, College of Graduate Studies and the College of Allied Health Sciences, Medical College of Georgia.
More information: https://dknet.org/about/webinar
With the passage of time, PROTACs technology has entered an unprecedented stage of development in recent years. According to the different requirements of customers, BOC Sciences can design, synthesize, optimize PROTAC molecules, establish analytical methods and carry out the biological evaluation. Please visit https://protac.bocsci.com for more information.
With the passage of time, PROTACs technology has entered an unprecedented stage of development in recent years. Scientists gradually see the absolute advantages of this technology, which can not only transform non-drug target (undruggable) into feasible drug target (druggable) but also resolve the problem of drug resistance of existing targets. In recent years, we have made great efforts to develop the (PROTAC) platform of protein degradation technology to provide research tools for small molecules targeting so-called non-proprietary drugs, in order to better help customers and help customers in the process of new drug research and development. According to the different requirements of customers, BOC Sciences can design, synthesize, optimize PROTAC molecules, establish analytical methods and carry out the biological evaluation.
Yeast two hybrid system for Protein Protein Interaction Studiesajithnandanam
Yeast Two Hybrid system uses a reporter gene to detect the interaction of pair of proteins inside the yeast cell nucleus. In the yeast Two Hybrid System, The interaction of target protein to the protein will bring together transcriptional activator, which then switches on the expression of reporter gene.
“Regulatory and Medical Aspects of Interchangeability of Biologicals and Biosimilars”
Provides an overview of regulatory and medical considerations on the interchangeability of biotherapeutic medicines
Product Overview
Viasil uses 100% natural ingredients for a safe and clinically tested
erectile dysfunction formula. Revolutionising bedroom
performance, Viasil increases energy levels, reawakens sexual
desire, supports hard powerful erections and extra stamina and
endurance.
Now even better than before thanks to the complementary Viasil -
Instant Erection Gel.
G Protein Coupled Receptor- An Introduction.Arindam Sain
The Largest family of integral membrane protein involved in many biological process and pathologies. 50% of all modern drugs and 25% of the top 200 best selling drugs are estimated to target GPCRs. Transduce the signals mediated by diverse signaling molecules, such as ions, peptides, lipids and photons, to induce different intracellular function. Bind their ligand and toa activate different G proteins.
With the passage of time, PROTACs technology has entered an unprecedented stage of development in recent years. According to the different requirements of customers, BOC Sciences can design, synthesize, optimize PROTAC molecules, establish analytical methods and carry out the biological evaluation. Please visit https://protac.bocsci.com for more information.
With the passage of time, PROTACs technology has entered an unprecedented stage of development in recent years. Scientists gradually see the absolute advantages of this technology, which can not only transform non-drug target (undruggable) into feasible drug target (druggable) but also resolve the problem of drug resistance of existing targets. In recent years, we have made great efforts to develop the (PROTAC) platform of protein degradation technology to provide research tools for small molecules targeting so-called non-proprietary drugs, in order to better help customers and help customers in the process of new drug research and development. According to the different requirements of customers, BOC Sciences can design, synthesize, optimize PROTAC molecules, establish analytical methods and carry out the biological evaluation.
Yeast two hybrid system for Protein Protein Interaction Studiesajithnandanam
Yeast Two Hybrid system uses a reporter gene to detect the interaction of pair of proteins inside the yeast cell nucleus. In the yeast Two Hybrid System, The interaction of target protein to the protein will bring together transcriptional activator, which then switches on the expression of reporter gene.
“Regulatory and Medical Aspects of Interchangeability of Biologicals and Biosimilars”
Provides an overview of regulatory and medical considerations on the interchangeability of biotherapeutic medicines
Product Overview
Viasil uses 100% natural ingredients for a safe and clinically tested
erectile dysfunction formula. Revolutionising bedroom
performance, Viasil increases energy levels, reawakens sexual
desire, supports hard powerful erections and extra stamina and
endurance.
Now even better than before thanks to the complementary Viasil -
Instant Erection Gel.
G Protein Coupled Receptor- An Introduction.Arindam Sain
The Largest family of integral membrane protein involved in many biological process and pathologies. 50% of all modern drugs and 25% of the top 200 best selling drugs are estimated to target GPCRs. Transduce the signals mediated by diverse signaling molecules, such as ions, peptides, lipids and photons, to induce different intracellular function. Bind their ligand and toa activate different G proteins.
Gold Standard Physiological Measurements and Novel Drug Delivery Methods - Se...InsideScientific
A 2-part webinar for scientists interested in novel drug delivery methods for basic research, drug discovery and development. Learn about novel infusion technologies and how challenges in physiological monitoring and drug delivery are being overcome by implantable and programmable devices.
Session 2: Synthetic, Structural, and Mechanistic Investigations of Vitamin B12 Conjugates of the Anorectic Peptide PYY3-36
Presenter: Dr. Robert Doyle, Syracuse University & SUNY, Upstate Medical University
Dr. Robert Doyle talks about how vitamin B12 conjugation of Peptide YY3-16 decreases food intake compared to native Peptide – YY3-36 in male rats. Learn how challenges to peptide-based therapies, such as rapid clearance, ready degradation by hydrolysis/proteolysis and poor intestinal uptake and/or a need for blood brain barrier transport can be overcome by using vitamin B12 in the subcutaneously administered drug delivery device iPrecio.
Dr. Praveen Balimane, senior staff fellow, Division of Clinical Pharmacology-1 at OCP/OTS/CDER/FDA, spoke during the Society for Laboratory Automation and Screening ADMET Special Interest Group Meeting on “Transporter Evaluation in Drug Development.”
Transporters, like CYPs, are being recognized as proteins that can play a pivotal role in dictating the ADME properties of drugs. A thorough understanding of potential roles of transporters in drug interactions and toxicity is important in drug development. The talk provided a high level overview of various transporter evaluation initiatives at the agency. Some of the topics discussed:
• On-going efforts on decision trees within the DDI guidance
• Novel emerging transporters impacting ADME
• Inter-play of hepatic transporters and liver-toxicity
• Inter-play of renal transporters and renal function
Intranasal delivery of drug loaded thiolated co-polymeric microparticles for...Gaurav Patil
E-Presentation at Two days 15th Indo-US virtual International Conference
on “Global advances in Pharmaceutical and Allied Science”
In collaboration with
APP Gujarat State branch, AAP American International branch,
AAP Pharmedu Healthcare Manag Division
2. Protein Interaction Partners of Protein Phosphatase 2A Catalytic Subunit
in Rat β-Islet cells Using Quantitative Mass Spectrometry
Divyasri Damacharla1,2; Khadija Syeda1,2 Xiangmin Zhang2; Danjun Ma2; Yue Qi2; Anjaneyulu Kowluru1,2; Zhengping Yi2
1John D. Dingell VA Medical Center and 2Wayne State University, Detroit, MI
INTRODUCTION
• Protein phosphatase 2A (PP2A) is one of the major
serine/threonine phosphatases
• Its activity is up regulated under glucolipotoxic
conditions in liver, retina and pancreatic islet cells
However, it remains unknown about the various
interactions of PP2Ac in rat pancreatic β islet cells that
may contribute to the increased PP2A activity and
regulation of cellular function
• Here, using HPLCE-ESI-MS/MS, we aimed to identify
the PP2Ac interaction partners involved in insulin
secretion or other pathways which may lead to
dysfunction or demise of the β-islet cells
METHODS
INS-1 832/13 cells
LOW GLUCOSE HIGH GLUCOSE
IMMUNOPRECIPITATION
SDS-PAGE
IN-GEL TRYPSIN DIGESTION; PEPTIDE ENRICHMENT
HPLC-MS/MS
MAXQUANT AND STATISTICALANALYSIS
RESULTS
SUMMARY
Proteins identified with minimum 2 unique peptides with FDR at
0.01 in at least one PP2Ac IP? (1131 proteins)
Identified with LFQ peak area (PA) in more than half (e.g., > 4
out of 8) PP2Ac IP samples? (514 proteins,)
Enrichment ratio for each protein determined. Enrichment ratio for
a protein > 10 (PP2Ac vs NIgG IP)? (606 proteins)
Normalized PA for PP2Ac interaction partners determined
P < 0.05 by independent t tests?
(89 proteins)
With a fold change greater than 1.5 (i.e., 1.5 fold increase) or
less than 0.67 (i.e., 1.5 fold decrease) HG vs. LG? (265 proteins)
Figure 1 statistical analysis and summary of the results obtained
• Largest PP2A interaction network till date in rat β-
islet cells
• Validation of the identified partners will give insight
into the regulation of PP2A
• Further validation of glucose responsive partners
will help understand role of PP2A under high
glucose conditions
• Significant complexes may be targeted later to alter
the composition and thereby prevent the demise of
the β-islet cells under glucotoxic conditions
• 514 PP2Ac interaction
partners
• 38 previously reported
leaving 476 novel partners
• 89 showed significant
difference in response to high
glucose treatment
• Ingenuity Pathway Analysis
of the 514 partners revealed
59 significantly enriched
pathways
• Manual literature search
revealed a number of
proteins involved in insulin
secretion and other related
cell functions (Fig 2)
Protein synthesis
RPL4, PRL9, RPL18A,
RPL30, EIF2B1
Vesicle trafficking
VPS52, VPS37A,
TSG101, Rab10, Eea1,
Rab5C
Protein degradation
UBR1, UBE2C, CNOT4,
CBR3
Membrane fusion
VAT1, SLMAP, Rab5c
Gluconeogenesis
WDR5
Anti-apoptosis
PPP4R1, CIAPIN1
Transcription control
VGLL4, TRIP11, STAT6,
PHF5A , NcoR1,
HIST1H1C, DDX17
PTM
UGGT1, WDR5, LIMK1, PPM1B,
PPP2R1B, PPP2R2A, PPP4R1, PPP6c
Membrane reshaping
TXNRD1, SLMAP,
SH3BP1
Insulin secretion
RhoA, Rab5c, PLA2G6,
PFKFB2, EIF2C2, APPL1
DNA damage/repair
LIG1, INST5, INST7,
INST12
Protein sorting, trafficking
GGA2, SRP72
Glucose flux control
GFPT1
PP2Ac
Figure 2 partners involved in various important functions
RESULTS