This document summarizes research on oxidative stress and inflammation in Alzheimer's disease. The researchers found that transgenic mice models of Alzheimer's disease showed an imbalance between pro-oxidant and anti-oxidant proteins, as well as between pro-inflammatory and anti-inflammatory mediators, compared to wild type mice. Specifically, microarray analysis found increased levels of pro-oxidants and pro-inflammatory genes and decreased levels of anti-oxidants and anti-inflammatory genes in the transgenic mice. This demonstrates oxidative stress and inflammation are features of Alzheimer's disease.
The bc1 complex provides reduced cytochrome c to either the aa3 or cbb3 oxidases depending on oxygen conditions in R. sphaeroides. Strain BC-17 cannot photosynthesize due to lack of bc1 complex reducing cbb3. Some H217 mutations in the QI site can photosynthesize with DMSO but revert or are lethal without it. Future work should introduce H217 mutations into a DorR-/PpsR- background to uncouple effects on bc1 from changes to photosystem expression levels.
This document describes research characterizing how changes in environmental conditions influence the physiology of Vibrio tubiashii using omics approaches. Experiments examined the response of V. tubiashii to low oxygen conditions and the presence of oysters. Proteomic analysis using 2D gels identified approximately 23 proteins that were upregulated under low oxygen conditions and 47 proteins upregulated under aerobic conditions. Gene expression analysis using qPCR monitored expression of several genes related to motility, chemotaxis, and virulence over 24 hours when exposed to oysters. RNA sequencing generated over 226 million base pairs of sequence data for gene discovery.
CD47 plays a role in nitric oxide signaling and angiogenesis by interacting with other proteins like thrombospondin-1 and vascular endothelial growth factor receptor-2. The document discusses experiments attempting to characterize CD47's role by tagging it with BirA to identify interacting proteins, expressing a truncated version of thrombospondin-1 to activate CD47 and measure calcium responses, and cloning CD47-BirA into a vector for expression. Preliminary results were inconclusive, suggesting the calcium assay and thrombospondin-1 purification need further optimization to understand CD47's signaling mechanisms.
Different mutations are created in the commercial host strains of E.coli which provide them with advantages as compared to the wild type strain. This presentation deals with few strains like Dh5alpha, DH10B, Bl21, JM109 E.coli strains and their associated mutations.
This document discusses peptides containing β-amino acid patterns and their applications in medicinal chemistry. It begins with an introduction to β-amino acids and their classification. Various methods for synthesizing β-amino acids are then reviewed, including metal catalysis, organocatalysis, and common reaction types. Applications discussed include using β-amino acid peptides for membrane targeting, mimicking protein functions like receptor binding, and as ligands for receptors involved in conditions like diabetes, cancer, and inflammation. The document concludes by noting the challenges and successes in developing bioactive molecules using β-amino acid peptide scaffolds.
This document summarizes research into the germline-specific function of DAF-18/PTEN in the nematode C. elegans. It describes how DAF-18 is required for larval arrest in C. elegans under unfavorable conditions. The researchers found that germline-specific knockdown of DAF-18 results in defective larval arrest, and that rescuing DAF-18 function only in the germline can correct this. They aim to identify upstream regulators of DAF-18 by observing changes in DAF-18 reporter fluorescence under RNAi knockdown of candidate genes. Integrating DAF-18 specifically in the germline under a germline promoter may
The bc1 complex provides reduced cytochrome c to either the aa3 or cbb3 oxidases depending on oxygen conditions in R. sphaeroides. Strain BC-17 cannot photosynthesize due to lack of bc1 complex reducing cbb3. Some H217 mutations in the QI site can photosynthesize with DMSO but revert or are lethal without it. Future work should introduce H217 mutations into a DorR-/PpsR- background to uncouple effects on bc1 from changes to photosystem expression levels.
This document describes research characterizing how changes in environmental conditions influence the physiology of Vibrio tubiashii using omics approaches. Experiments examined the response of V. tubiashii to low oxygen conditions and the presence of oysters. Proteomic analysis using 2D gels identified approximately 23 proteins that were upregulated under low oxygen conditions and 47 proteins upregulated under aerobic conditions. Gene expression analysis using qPCR monitored expression of several genes related to motility, chemotaxis, and virulence over 24 hours when exposed to oysters. RNA sequencing generated over 226 million base pairs of sequence data for gene discovery.
CD47 plays a role in nitric oxide signaling and angiogenesis by interacting with other proteins like thrombospondin-1 and vascular endothelial growth factor receptor-2. The document discusses experiments attempting to characterize CD47's role by tagging it with BirA to identify interacting proteins, expressing a truncated version of thrombospondin-1 to activate CD47 and measure calcium responses, and cloning CD47-BirA into a vector for expression. Preliminary results were inconclusive, suggesting the calcium assay and thrombospondin-1 purification need further optimization to understand CD47's signaling mechanisms.
Different mutations are created in the commercial host strains of E.coli which provide them with advantages as compared to the wild type strain. This presentation deals with few strains like Dh5alpha, DH10B, Bl21, JM109 E.coli strains and their associated mutations.
This document discusses peptides containing β-amino acid patterns and their applications in medicinal chemistry. It begins with an introduction to β-amino acids and their classification. Various methods for synthesizing β-amino acids are then reviewed, including metal catalysis, organocatalysis, and common reaction types. Applications discussed include using β-amino acid peptides for membrane targeting, mimicking protein functions like receptor binding, and as ligands for receptors involved in conditions like diabetes, cancer, and inflammation. The document concludes by noting the challenges and successes in developing bioactive molecules using β-amino acid peptide scaffolds.
This document summarizes research into the germline-specific function of DAF-18/PTEN in the nematode C. elegans. It describes how DAF-18 is required for larval arrest in C. elegans under unfavorable conditions. The researchers found that germline-specific knockdown of DAF-18 results in defective larval arrest, and that rescuing DAF-18 function only in the germline can correct this. They aim to identify upstream regulators of DAF-18 by observing changes in DAF-18 reporter fluorescence under RNAi knockdown of candidate genes. Integrating DAF-18 specifically in the germline under a germline promoter may
Structural Modeling of the Ptf1a C2 Sequence Bound to Mammalian Rbpj and RbjlWard Coats
In this study, the researchers:
1) Generated structural models of the C2 sequence of Ptf1a bound to the β-trefoil domains of mammalian Rbpj and Rbpjl.
2) Found that the C2 sequence binds in an extended conformation, maintaining interactions seen in the Notch-IC/Rbpj complex.
3) Observed conserved residues in the hydrophobic pocket that maintain binding of proteins with a conserved tryptophan motif.
Cloning of candida antarctica lipase a gene in to kluveromyces lactisRajarajan Panneerselvam
This document describes cloning the lipase A (CALA) gene from Candida antarctica into the Kluveromyces lactis expression system using the pKLAC2 vector. Key steps include:
1. Amplifying the CALA gene from C. antarctica and restricting it with XhoI.
2. Extracting and restricting pKLAC2 with XhoI.
3. Ligating the CALA insert into linearized pKLAC2.
4. Transforming E. coli with the ligation mixture and confirming transformants contain the CALA insert through colony PCR and plasmid extraction.
1. Cellular signal transduction involves signaling molecules, receptors, and intracellular signal transduction pathways that allow cells to respond to changes in their external environment.
2. Signaling molecules like hormones, neurotransmitters, cytokines, and gas molecules bind to membrane or intracellular receptors to activate downstream signaling pathways.
3. The main intracellular signaling pathways include the cAMP/PKA pathway, Ca2+/PKC pathway, cGMP/PKG pathway, and tyrosine kinase pathways which result in phosphorylation of target proteins and regulation of gene expression.
β-lactam antibiotics work by inhibiting bacterial cell wall synthesis. There are several classes of β-lactam antibiotics including penicillins, cephalosporins, monobactams, and carbapenems. Penicillins are derived from Penicillium fungi and contain a thiazolidine ring fused to the β-lactam ring. Cephalosporins are derived from the fungus Cephalosporium and contain a dihydrothiazine ring fused to the β-lactam ring. Both penicillins and cephalosporins target bacterial transpeptidases to inhibit cell wall crosslinking. Structural modifications to these classes of β-lactams can
Lipoproteins are complexes of lipids and proteins that transport cholesterol, triglycerides, and fat-soluble vitamins throughout the body. They can be classified based on density and size into different classes, including chylomicrons, VLDLs, IDLs, LDLs, and HDLs. The major apolipoproteins associated with each lipoprotein class help to assemble particles and activate enzymes involved in lipoprotein metabolism. Disorders can cause abnormal accumulation of certain lipoprotein classes and are classified according to the Frederickson system.
Thisppy contains few solved questions of GATE 2009 examination along with explanations. This will be helpful for all those who are preparing for GATE, CSIR, UGC NET, etc. Complete set of questions along with answers and explanations can be viewed at http://purnasrinivas.weebly.com
This document discusses cellular signalling and molecular mechanisms of drug action. It describes the different types of cell signalling including extracellular signals like hormones and intracellular signals like calcium and cyclic nucleotides. It also explains different receptor types like G-protein coupled receptors and ligand-gated ion channels. Additionally, it covers molecular mechanisms of drug action like receptor occupancy models and transducer mechanisms. Finally, it discusses ion channels involved in cellular signalling like sodium, calcium and potassium channels as well as their pharmacological modulation.
RNase contamination was preventing accurate measurement of RNA-protein binding between LARP6 and its RNA substrate. The researchers optimized native polyacrylamide gel electrophoresis with biotinylated RNA to visualize and quantify binding. They showed biotinylation worked without detecting RNase contamination. Continued gel condition optimization will improve resolution for determining the functional boundaries of the LARP6 La Module domain required for RNA binding.
The document describes a concise total synthesis of the prolyl endopeptidase inhibitor eurystatin A via a novel multi-step strategy. Key steps include:
1) A three-component Passerini reaction between suitably protected alaninal, leucine isonitrile, and ornithine components to deliver adducts 10a,b in high yield.
2) Orthogonal N-deprotection of 10a led, via a smooth O- to N-acyl migration, to 11, which constitutes the entire skeleton of the eurystatins.
3) Subsequent deprotection, macrocyclization, elaboration, and final oxidation steps efficiently afforded
The document discusses several genetics concepts:
- Tobacco mosaic virus has RNA rather than DNA as its genetic material. A hybrid virus could result from mixing its RNA with proteins from a related DNA virus.
- In DNA, cytosine makes up 38% of nucleotides in a sample. This means thymine would make up 31% of nucleotides.
- DNA replication is described as being either conservative, semiconservative, or dispersive based on experimental results using nitrogen isotopes.
- The genetic code and how mRNA is translated to produce proteins is also covered.
El documento describe las opiniones de una persona sobre el futuro de las computadoras y las aplicaciones relacionadas con su profesión. Imagina que las computadoras estarán más enfocadas en la privacidad de la información y que se podrá acceder a ellas de forma virtual desde cualquier lugar. También menciona aplicaciones como Excel, Fear Not y sistemas de evaluación de personal que utiliza actualmente o cree que utilizará, clasificándolas según su licencia. Finalmente propone que las aplicaciones deberían ser más didácticas y presentar solo las herramientas necesari
The free two-part "Passion for Birth" childbirth education class will cover Lamaze principles and topics like natural birth, informed decision making, coping with pain, avoiding unnecessary medical interventions, keeping mom and baby together after birth, breastfeeding basics, and postpartum support. The classes will be held on February 23 and March 2 from 9AM to 3PM at a location TBA. For more details or to register, contact Stephanie via email, Facebook, or phone. The instructor is in the process of Lamaze certification but is offering this class for free as part of her training requirements.
Manuel Ramos Bartilotti worked as a Pipefitter for N-Ren International at their Chemical Fertilizer Complex in Tamatave, Madagascar from January 1985 to December 1985. He satisfactorily completed his work agreement. The certificate was signed by the Project Director, Fred P. Auzenne.
This document provides a production plan and checklist for filming an interview project. It outlines key tasks such as conducting a location recce, risk assessment, determining shot types and interview conventions. It also describes arranging interviews through texts and emails, selecting expert interviewees, and developing interview questions. Additionally, it mentions including pictures of setting up shots, a storyboard, and a filming schedule or checklist. The overall purpose is to help the group stay organized and know what needs to be done for the interview project.
Miss Saie Saraf is seeking an engineering position where she can utilize her electrical engineering knowledge and programming skills. She has a Master of Science in electrical and computer engineering from Rutgers University and a Bachelor of Engineering from Cummins College of Engineering in India. She has excellent knowledge of programming languages including C, C++, Java, Python and experience with PLCs, MATLAB, and PHP. She has worked as an intern at Cummins Turbo Technologies and as an Assistant Manager at Cummins India in research and development. Some of her projects include implementing an algorithm for finding shortest paths in large social graphs and developing a rotating viscometer to measure engine oil viscosity.
Discovery and optimization of novel small molecule HIV-1 entry inhibitors usi...Cresset
This document describes efforts to discover novel small molecule HIV-1 entry inhibitors. Researchers used field-based virtual screening and bioisosteric replacement to identify potential inhibitors. They tested 50 compounds and found 4 with sub-100nM potency against HIV-1, representing new "core" chemotypes. The most potent compound had an IC50 of 0.6nM. Through de novo design and structure-property analysis, they further improved potency and drug-likeness, identifying additional leads with low nanomolar potency and improved predicted drug-like properties. This work demonstrates an effective structure-based approach to discover new HIV-1 entry inhibitors.
Discovery and optimization of novel small molecule HIV-1 entry inhibitors usi...Cresset
This document describes the discovery and optimization of novel small molecule HIV-1 entry inhibitors. Using field-based virtual screening and bioisosteric replacement, the authors identified several new inhibitor scaffolds with improved potency and drug-like properties compared to existing inhibitors. Through iterative rounds of in silico screening, medicinal chemistry optimization, and testing, they developed inhibitors with IC50 values as low as 1 nM against HIV-1 entry. The best inhibitors represented new chemotypes including pyrrolo-pyrazole and dipyrrolidine scaffolds.
Structural Modeling of the Ptf1a C2 Sequence Bound to Mammalian Rbpj and RbjlWard Coats
In this study, the researchers:
1) Generated structural models of the C2 sequence of Ptf1a bound to the β-trefoil domains of mammalian Rbpj and Rbpjl.
2) Found that the C2 sequence binds in an extended conformation, maintaining interactions seen in the Notch-IC/Rbpj complex.
3) Observed conserved residues in the hydrophobic pocket that maintain binding of proteins with a conserved tryptophan motif.
Cloning of candida antarctica lipase a gene in to kluveromyces lactisRajarajan Panneerselvam
This document describes cloning the lipase A (CALA) gene from Candida antarctica into the Kluveromyces lactis expression system using the pKLAC2 vector. Key steps include:
1. Amplifying the CALA gene from C. antarctica and restricting it with XhoI.
2. Extracting and restricting pKLAC2 with XhoI.
3. Ligating the CALA insert into linearized pKLAC2.
4. Transforming E. coli with the ligation mixture and confirming transformants contain the CALA insert through colony PCR and plasmid extraction.
1. Cellular signal transduction involves signaling molecules, receptors, and intracellular signal transduction pathways that allow cells to respond to changes in their external environment.
2. Signaling molecules like hormones, neurotransmitters, cytokines, and gas molecules bind to membrane or intracellular receptors to activate downstream signaling pathways.
3. The main intracellular signaling pathways include the cAMP/PKA pathway, Ca2+/PKC pathway, cGMP/PKG pathway, and tyrosine kinase pathways which result in phosphorylation of target proteins and regulation of gene expression.
β-lactam antibiotics work by inhibiting bacterial cell wall synthesis. There are several classes of β-lactam antibiotics including penicillins, cephalosporins, monobactams, and carbapenems. Penicillins are derived from Penicillium fungi and contain a thiazolidine ring fused to the β-lactam ring. Cephalosporins are derived from the fungus Cephalosporium and contain a dihydrothiazine ring fused to the β-lactam ring. Both penicillins and cephalosporins target bacterial transpeptidases to inhibit cell wall crosslinking. Structural modifications to these classes of β-lactams can
Lipoproteins are complexes of lipids and proteins that transport cholesterol, triglycerides, and fat-soluble vitamins throughout the body. They can be classified based on density and size into different classes, including chylomicrons, VLDLs, IDLs, LDLs, and HDLs. The major apolipoproteins associated with each lipoprotein class help to assemble particles and activate enzymes involved in lipoprotein metabolism. Disorders can cause abnormal accumulation of certain lipoprotein classes and are classified according to the Frederickson system.
Thisppy contains few solved questions of GATE 2009 examination along with explanations. This will be helpful for all those who are preparing for GATE, CSIR, UGC NET, etc. Complete set of questions along with answers and explanations can be viewed at http://purnasrinivas.weebly.com
This document discusses cellular signalling and molecular mechanisms of drug action. It describes the different types of cell signalling including extracellular signals like hormones and intracellular signals like calcium and cyclic nucleotides. It also explains different receptor types like G-protein coupled receptors and ligand-gated ion channels. Additionally, it covers molecular mechanisms of drug action like receptor occupancy models and transducer mechanisms. Finally, it discusses ion channels involved in cellular signalling like sodium, calcium and potassium channels as well as their pharmacological modulation.
RNase contamination was preventing accurate measurement of RNA-protein binding between LARP6 and its RNA substrate. The researchers optimized native polyacrylamide gel electrophoresis with biotinylated RNA to visualize and quantify binding. They showed biotinylation worked without detecting RNase contamination. Continued gel condition optimization will improve resolution for determining the functional boundaries of the LARP6 La Module domain required for RNA binding.
The document describes a concise total synthesis of the prolyl endopeptidase inhibitor eurystatin A via a novel multi-step strategy. Key steps include:
1) A three-component Passerini reaction between suitably protected alaninal, leucine isonitrile, and ornithine components to deliver adducts 10a,b in high yield.
2) Orthogonal N-deprotection of 10a led, via a smooth O- to N-acyl migration, to 11, which constitutes the entire skeleton of the eurystatins.
3) Subsequent deprotection, macrocyclization, elaboration, and final oxidation steps efficiently afforded
The document discusses several genetics concepts:
- Tobacco mosaic virus has RNA rather than DNA as its genetic material. A hybrid virus could result from mixing its RNA with proteins from a related DNA virus.
- In DNA, cytosine makes up 38% of nucleotides in a sample. This means thymine would make up 31% of nucleotides.
- DNA replication is described as being either conservative, semiconservative, or dispersive based on experimental results using nitrogen isotopes.
- The genetic code and how mRNA is translated to produce proteins is also covered.
El documento describe las opiniones de una persona sobre el futuro de las computadoras y las aplicaciones relacionadas con su profesión. Imagina que las computadoras estarán más enfocadas en la privacidad de la información y que se podrá acceder a ellas de forma virtual desde cualquier lugar. También menciona aplicaciones como Excel, Fear Not y sistemas de evaluación de personal que utiliza actualmente o cree que utilizará, clasificándolas según su licencia. Finalmente propone que las aplicaciones deberían ser más didácticas y presentar solo las herramientas necesari
The free two-part "Passion for Birth" childbirth education class will cover Lamaze principles and topics like natural birth, informed decision making, coping with pain, avoiding unnecessary medical interventions, keeping mom and baby together after birth, breastfeeding basics, and postpartum support. The classes will be held on February 23 and March 2 from 9AM to 3PM at a location TBA. For more details or to register, contact Stephanie via email, Facebook, or phone. The instructor is in the process of Lamaze certification but is offering this class for free as part of her training requirements.
Manuel Ramos Bartilotti worked as a Pipefitter for N-Ren International at their Chemical Fertilizer Complex in Tamatave, Madagascar from January 1985 to December 1985. He satisfactorily completed his work agreement. The certificate was signed by the Project Director, Fred P. Auzenne.
This document provides a production plan and checklist for filming an interview project. It outlines key tasks such as conducting a location recce, risk assessment, determining shot types and interview conventions. It also describes arranging interviews through texts and emails, selecting expert interviewees, and developing interview questions. Additionally, it mentions including pictures of setting up shots, a storyboard, and a filming schedule or checklist. The overall purpose is to help the group stay organized and know what needs to be done for the interview project.
Miss Saie Saraf is seeking an engineering position where she can utilize her electrical engineering knowledge and programming skills. She has a Master of Science in electrical and computer engineering from Rutgers University and a Bachelor of Engineering from Cummins College of Engineering in India. She has excellent knowledge of programming languages including C, C++, Java, Python and experience with PLCs, MATLAB, and PHP. She has worked as an intern at Cummins Turbo Technologies and as an Assistant Manager at Cummins India in research and development. Some of her projects include implementing an algorithm for finding shortest paths in large social graphs and developing a rotating viscometer to measure engine oil viscosity.
Discovery and optimization of novel small molecule HIV-1 entry inhibitors usi...Cresset
This document describes efforts to discover novel small molecule HIV-1 entry inhibitors. Researchers used field-based virtual screening and bioisosteric replacement to identify potential inhibitors. They tested 50 compounds and found 4 with sub-100nM potency against HIV-1, representing new "core" chemotypes. The most potent compound had an IC50 of 0.6nM. Through de novo design and structure-property analysis, they further improved potency and drug-likeness, identifying additional leads with low nanomolar potency and improved predicted drug-like properties. This work demonstrates an effective structure-based approach to discover new HIV-1 entry inhibitors.
Discovery and optimization of novel small molecule HIV-1 entry inhibitors usi...Cresset
This document describes the discovery and optimization of novel small molecule HIV-1 entry inhibitors. Using field-based virtual screening and bioisosteric replacement, the authors identified several new inhibitor scaffolds with improved potency and drug-like properties compared to existing inhibitors. Through iterative rounds of in silico screening, medicinal chemistry optimization, and testing, they developed inhibitors with IC50 values as low as 1 nM against HIV-1 entry. The best inhibitors represented new chemotypes including pyrrolo-pyrazole and dipyrrolidine scaffolds.
System response of metabolic networks in Chlamydomonas reinhardtii during Nit...Nishikant Wase
Nitrogen starvation induces a global stress response in microalga that results in the accumulation of triglycerides in lipid bodies. To identify components and mechanisms leading to lipid accumulation during nitrogen stress, we used GC-MS based metabolite profiling and iTRAQ based quantitative proteomics to examine Chlamydomonas reinhardtii cultured up to 144 hours without nitrogen. When nitrogen is limiting, starch and lipid accumulated rapidly, with lipid becoming the major storage compound by 144 hours. Our FAMEs data showed that the percentage of highly unsaturated fatty acids was reduced and the percentage of saturated and monounsaturated fatty acids were increased. Using information from the GC-MS based metabolite profiling; a Partial Least Squares Discriminant Analysis model was created to evaluate the role of different intracellular metabolites during lipid accumulation. We observed decreased abundance of key amino acids whereas some important metabolites including citric acid, trehalose, triethanolamine, nicotinamine, methnionine, citramalic acid and sorbitol were increased in abundance. Addition of citric acid (from 4 mM to 6 mM) to the growth media significantly improves the lipid yield in Chlamydomonas reinhardtii while growing in TAP media containing nitrogen. Examination of differentially expressed proteins revealed that 100 of 793 identified proteins were induced after 144 hours, while 77 proteins were reduced in abundance. Proteins involved in nitrogen assimilation, oxidative phosphorylation, the glycolytic pathway, TCA cycle, starch, and lipid metabolism were found to be higher in abundance than in non-stressed cultures. Another effect of nitrogen starvation was reduction of proteins of the photosynthetic apparatus (including PS-I and PS-II) and light harvesting complex proteins. We conclude that during nitrogen starvation, carbon availability is the most important factor controlling oil biosynthesis and that there is carbon partitioning between starch and oil synthesis.
JACS-CD38 localization using a fluorescent probeJonathan Shrimp
This document describes the development of a fluorescent small molecule probe called SR101−F-araNMN that can label the enzyme CD38 in live cells in a mechanism-based manner. The probe was used to investigate the cellular localization of CD38 in leukemia (HL-60 and K562) and lymphoma (Raji) cell lines. The results showed that CD38 is predominantly localized to the plasma membrane in Raji and RA-treated HL-60 cells, with very little intracellular CD38. Additionally, no CD38 expression was detected in K562 cells. This suggests that the major function of CD38 is to hydrolyze extracellular rather than intracellular NAD.
This document discusses tetracycline antibiotics. It begins by describing tetracyclines' chemical structure as consisting of 4 fused hydrocarbon rings. Tetracyclines are broad-spectrum antibiotics produced by Streptomyces bacteria. They inhibit protein synthesis by preventing aminoacyl-tRNA from attaching to the mRNA-ribosome complex. The document then discusses the pharmacology, mechanisms of action, structural activity relationships, selected drugs, and therapeutic uses of tetracyclines.
Cyclin D1 plays a direct role in DNA repair by interacting with proteins involved in homologous recombination. It was found to directly interact with and help recruit RAD51 to DNA damage sites, facilitating efficient DNA repair. Cyclin D1 also interacts with the C-terminus of BRCA2, helping recruit RAD51 by preventing inhibitory phosphorylation of BRCA2 by cyclin A/CDK2. Depletion of cyclin D1 impairs RAD51 focus formation and homologous recombination after DNA damage. These findings establish a novel function of cyclin D1 in promoting accurate DNA repair through homologous recombination.
This study investigated the effects of bile acids on expression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in human hepatocytes. The following key points are summarized:
1) Treatment with chenodeoxycholic acid (CDCA) significantly decreased both PCSK9 mRNA and protein levels in immortalized human hepatocytes.
2) Activation of the farnesoid X receptor (FXR) by its synthetic agonist GW4064 also decreased PCSK9 expression.
3) Coadministration of CDCA counteracted the statin-induced increase in PCSK9 expression, leading to a potentiation of low-density lip
- WPE-stem cells, a type of human prostate progenitor/stem cell, were initially highly sensitive to cadmium exposure, experiencing 90% cell loss after one week compared to 15% for a differentiated cell line. However, the stem cells quickly adapted and recovered their numbers within 4 weeks.
- During chronic cadmium exposure, the stem cells acquired characteristics of cancer cells like increased MMP-9 levels and colony formation along with decreased expression of tumor suppressors. They also showed signs of epithelial-mesenchymal transition.
- The initial sensitivity was linked to increased apoptosis factors while the later adaptation involved upregulation of cadmium resistance factors like metallothionein and downregulation of cadmium
L'identification du rôle principal du gène pfcrt dans le mécanisme de chloroquino-résistance chez Plasmodium falciparum - Conférence de la 2e édition du Cours international « Atelier Paludisme » - FIDOCK David - Albert Einstein College of Medicine - USA - dfidock@aecom.yu.edu
The document discusses several topics related to the complement system and immunoassays:
1) It describes the complement system as part of the immune system that enhances the ability of antibodies and phagocytes to clear pathogens. It is activated via three pathways: classical, lectin, and alternative.
2) It explains the processes of complement activation, including the formation of C3 and C5 convertases that cleave complement proteins and amplification of the response.
3) It discusses two types of immunoassays - radioimmunoassay (RIA) and immunofluorescence. RIA uses radioactive labels on antigens or antibodies to measure concentrations via competition binding assays. Immunofluorescence utilizes fluorescent-labeled antibodies to detect target antigens
Human aldo-keto reductases (AKR) of the 1A, 1B, 1C and 1D subfamilies are involved in the pre-receptor regulation of nuclear (steroid hormone and orphan) receptors by regulating the local concentrations of their lipophilic ligands. AKR1C3 is one of the most interesting isoforms. It was cloned from human prostate and the recombinant protein was found to function as a 3-, 17- and 20-ketosteroid reductase with a preference for the conversion of Δ4-androstene-3,17- dione to testosterone implicating this enzyme in the local production of active androgens within the prostate. Using a validated isoform specific real-time RT-PCR procedure the AKR1C3 transcript was shown to be more abundant in primary cultures of epithelial cells than stromal cells, and its expression in stromal cells increased with benign and malignant disease. Using a validated isoform specific monoclonal Ab, AKR1C3 protein expression was also detected in prostate epithelial cells by immunoblot analysis.
Immunohistochemical staining of prostate tissue showed that AKR1C3 was expressed in adenocarcinoma and surprisingly high expression was observed in the endothelial cells. These cells are a rich source of prostaglandin G/H synthase 2 (COX-2) and
vasoactive prostaglandins (PG) and thus the ability of recombinant AKR1C enzymes to act as PGF synthases was compared. AKR1C3 had the highest catalytic efficiency (kcat/Km) for the 11-ketoreduction of PGD2 to yield 9α,11β-PGF2 raising the prospect that AKR1C3 may govern ligand access to peroxisome proliferator activated receptor (PPARγ). Activation of PPARγ is often a pro-apoptotic signal and/or leads to terminal differentiation, while 9α,11β- PGF2 is a pro-proliferative signal. AKR1C3 is potently inhibited by non-steroidal anti- inflammatory drugs suggesting that the cancer chemopreventive properties of these agents may be mediated either by inhibition of AKR1C3 or COX. To discriminate between these effects we developed potent AKR1C inhibitors based on N-phenylanthranilic acids that do not inhibit COX-1 or COX-2. These compounds can now be used to determine the role of AKR1C3 in producing two proliferative signals in the prostate namely testosterone and 9α,11β-PGF2.
The document discusses several topics related to the cell cycle, including cyclin bistability, polo-like kinase 1 (Plk1), checkpoints, and restarting the cell cycle after DNA damage. Plk1 plays a key role in controlling recovery from cell cycle arrest and checkpoint silencing through phosphorylation of Wee1 and Cdc25. There are feedback loops and an interdependent sequence of events that commit the cell to mitotic entry.
Rituxan lysis of B-cells is sensitive to multiple parameters including the level of CD20 expression and constituents of serum. Newer monoclonal antibodies attempt to increase antibody-dependent cell cytotoxicity (ADCC) at the cost of complement-dependent cytotoxicity (CDC) effectiveness, but success relies on sufficient stimulated effector cells in vivo. Dehydroepiandrosterone sulfate (DHEAS) is a potential stimulant of natural killer (NK) cell cytotoxicity found in human serum. Studies show DHEAS enhances NK cell cytotoxicity through protein kinase C-beta II activation and locally generated insulin-like growth factor 1, offering a potential mechanism by which serum augments cytotoxicity beyond media alone.
The document summarizes an experiment to clone the Arabidopsis ABC transporter gene Atwbc19 tagged with a C-terminal GFP fusion. Key steps included PCR amplification of Atwbc19, cloning it into an entry vector, recombining it into a destination vector using an LR reaction, transforming Agrobacterium, and identifying positive clones via restriction digest. Two clones were identified that contained the correct plasmid as shown by restriction fragments of the expected sizes. The conclusion states that Atwbc19 was successfully cloned with C-terminal GFP tagging to allow future monitoring of expression levels via microscopy and western blotting.
Raltegravir was the first HIV integrase inhibitor discovered. It was developed through extensive medicinal chemistry efforts at IRBM Science Park, optimizing properties like potency, pharmacokinetics, and resistance profile. Key developments included investigating substitutions on pyrimidine-based scaffolds and ultimately identifying the N-methylpyrimidinone series. Raltegravir demonstrated potent antiviral activity against HIV with no observed toxicity in clinical trials. Its approval in 2007 marked a new class of antiretroviral drugs for treating HIV infection.
Chemical Evolution of B Lactams to Keep Pace with Bacterial Resistancewarwick_amr
This document discusses the evolution of bacterial resistance to β-lactam antibiotics and efforts to develop new β-lactams to overcome resistance. It describes how resistance has emerged through production of β-lactamases and alterations of penicillin-binding proteins. It also summarizes research on using β-lactams to probe the structure and reaction mechanism of penicillin-binding proteins from different resistant bacteria. The goal was to develop β-lactams that cause stabilizing conformational changes and inhibit drug-resistant penicillin-binding proteins.
1) The document describes an in-silico drug discovery project to identify inhibitors of the influenza virus polymerase PB1-PB2 protein complex.
2) The researchers used computational modeling techniques like benzene mapping, pharmacophore modeling, and molecular docking to identify potential binding sites on the PB1-PB2 complex and screen databases of drug-like molecules to discover top hit compounds.
3) Their methodology identified 50 top hit compounds from an initial screening that were further analyzed in secondary screening, and the 4 compounds with highest binding energies were identified as potential leads for inhibiting the PB1-PB2 interaction and warrant further testing in viral replication assays.
Lymphocytes can be obtained from non-coagulating blood treated with either heparin or EDTA/citrate to prevent clotting. Flow cytometry uses monoclonal antibodies against cell surface markers like CD3, CD4, CD8, CD19, CD20, CD16, CD56, CD14 and DR to identify T cells, B cells, NK cells and monocytes. Laboratory investigation of lymphocytes includes enumerating subsets by surface markers, proliferation tests using specific or polyclonal mitogens to evaluate response, and delayed-type hypersensitivity tests using antigens to assess cell-mediated immunity.
1) Researchers studied the temperature-sensitive yeast mutant cdc20-1, which causes cell cycle arrest at metaphase. They hypothesized the mutation affects protein binding, stability, or folding.
2) Fluorescence microscopy showed cdc20-1-GFP localized to the nucleus at room temperature but the vacuole at 37°C, suggesting involvement of the unfolded protein response.
3) Molecular dynamics simulations indicated wild type and mutant Cdc20 had similar stability at permissive and non-permissive temperatures, suggesting defects in protein folding rather than stability.
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core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
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The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
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Remote Sensing and Geographic Information Systems
9
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BÀI TẬP DẠY THÊM TIẾNG ANH LỚP 7 CẢ NĂM FRIENDS PLUS SÁCH CHÂN TRỜI SÁNG TẠO ...
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1. OXIDATIVE STRESS AND INFLAMMATION IN ALZHEIMER´S DISEASE
1D. Aguirre-Rueda, 2C.
García-Lucerga, Sanchez-Pérez y Valles. 1A. 1S.L
1Departamento de Fisiología, Universidad de Valencia, España.
2Departamento de Fisioterapia, Universidad de Valencia, España.
Introduction
Many studies have shown the relationship between oxidative stress and Alzheimer’s disease (AD). The hallmark in AD is both accumulation of beta-amyloid plates and the presence of TAU protein inside
neurons. Furthermore, glial cell activation, occurs after plates appear in brain damaged, producing astrogliosis and microglia activation. Our group has shown oxidative stress and inflammation in neurons and
astrocytes in primary culture. Using microarray and RT-PCR we mid gene expression of oxidative stress and inflammation genes. Also, by western-blot we determine protein expression of inflammation and
oxidative stress markers in transgenic (APP/Preseniline I) compared with wild type mice.
Our results show an induction of pro-inflammatory mediators and reduction of anti-inflammatory mediators in transgenic mice compared with wild type. Also pro-oxidants proteins are increased and anti-oxidants
proteins are decreased in transgenic mice compared with wild type. Our results demonstrate an unbalance between oxidants and antioxidants proteins and also an unbalance between inflammatory and anti
inflammatory mediators in transgenic mice compared with wild type.
Function Gene identifier Gene name Fold change Direction
Abcf1 ATP- binding cassette sub-family F (GCN20) member 1 2,190899034 Up
Bcl6 B-cell leukemia/lymphoma 6 1,073880901 Down
Blr1 Burkit lymphoma receptor 1
C3 Complement component 3 2,44336433 Down
Casp1 Caspase 1 1,188429235 Down
Chemokine Genes Ccl1 Chemokine (C-C motif) ligand 1
Ccl11 Small chemokine (C-C motif) ligand 11 125,6433061 Down
Ccl12 Chemokine (C-C motif) ligand 12 19,96916357 Down
Ccl17 Chemokine (C-C motif) ligand 17 31,44884221 Down
Ccl19 Chemokine (C-C motif) ligand 19 4,63108745 Down
Ccl2 Chemokine (C-C motif) ligand 2 1,199760966 Down
Ccl20 Chemokine (C-C motif) ligand 20
Ccl22 Chemokine (C-C motif) ligand 22 1,188159073 Down
Ccl24 Chemokine (C-C motif) ligand 24 1,949822776 Down
Ccl25 Chemokine (C-C motif) ligand 25 420,1381549 Down
Ccl3 Chemokine (C-C motif) ligand 3 3,370891052 Up
Ccl4 Chemokine (C-C motif) ligand 4 3,104198899 Up
Ccl5 Chemokine (C-C motif) ligand 5 1,572800843 Down
Ccl6 Chemokine (C-C motif) ligand 6 1,352626009 Down
Ccl7 Chemokine (C-C motif) ligand 7 12,22641045 Down
Ccl8 Chemokine (C-C motif) ligand 8 13,6617747 Down Fig. 2.- Microarray of pro and anti-inflammatory proteins, transgenic (T) vs. wild type (C). RNA
Ccl9 Chemokine (C-C motif) ligand 9 3,258265123 Down obtained from 7th months cortex samples of female wild type and transgenic mice. Microarray
Chemokine ReceptorsCcr1 Chemokine (C-C motif) receptor 1 3,147601716 Down determined different pro-inflammatory and anti-inflammatory mediators.
Ccr2 Chemokine (C-C motif) receptor 2 15,91510754 Down
Ccr3 Chemokine (C-C motif) receptor 3 451,3538177 Down
Ccr4 Chemokine (C-C motif) receptor 4 12,99372345 Down
Ccr5 Chemokine (C-C motif) receptor 5 16,58895381 Down
Ccr6 Chemokine (C-C motif) receptor 6 10,2553086 Down
Ccr7 Chemokine (C-C motif) receptor 7 4,804342487 Down
Ccr8 Chemokine (C-C motif) receptor 8
Ccr9 Chemokine (C-C motif) receptor 9 99,3292009 Down
Crp C-reactive protein , pentraxin-related
Chemochine Genes Cx3cl1 Chemokine (C-X3-C motif) ligand 1 1,722094127 Down
Cxcl1 Chemokine (C-X-C motif) ligand 1
Cxcl10 Chemokine (C-X-C motif) ligand 10 7,17520972 Down
Cxcl11 Chemokine (C-X-C motif) ligand 11 5,252946897 Down
Cxcl12 Chemokine (C-X-C motif) ligand 12 1,297114647 Up
Cxcl13 Chemokine (C-X-C motif) ligand 13 1,543493064 Down
Cxcl15 Chemokine (C-X-C motif) ligand 15
Cxcl4 Chemokine (C-X-C motif) ligand 4 10,87836626 Down
Cxcl5 Chemokine (C-X-C motif) ligand 5 3,647019719 Down
Cxcl9 Chemokine (C-X-C motif) ligand 9 30,3151068 Down
Chemochine Receptors xcr3
C Chemokine (C-X-C motif) receptor 3
Ccr10 Chemokine (C-X-C motif) receptor 10 26,05351281 Down
Cytokine Genes Ifng Interferon gamma
Il10 Interleukin 10
Cytokine Receptors Il10ra Interleukin receptor, alpha 1,626417902 Down
Fig. 3.- Microarray of pro and anti-inflammatory proteins, wild type (C) vs. transgenic (T). RNA obtained
Il10rb Interleukin receptor, beta 2,428618699 Down from 7th months cortex samples of female wild type and transgenic mice. Microarray determined different
Cytokine Genes Il11 Interleukin 11 1,021726457 Down pro-inflammatory and anti-inflammatory mediators.
Il13 Interleukin 13
Cytokine Receptors Il13ra1 Interleukin 13 receptor, alpha 1 1,39337347 Down
Cytokine Genes Il15 Interleukin 15 1,373355383 Down
Il16 Interleukin 16 7,437635259 Down 0,18
Wild type P53
Il17b Interleukin 17B 14,38089939 Down
0,16
Relative Densitometric Units
Il18 Interleukin 18 1,856765987 Down Transgenic
0,14
Il1a Interleukin 1 alpha 3,289380724 Down
Il1b Interleukin 1 beta 2,297379193 Down 0,12
Il1f6 Interleukin 1 family, member 6 0,10 *
Il1f8 Interleukin 1 family, member 8 0,08
*
Il1r1 Interleukin 1 receptor, type I 1,005220501 Down 0,06 *
il1r2 Interleukin 1 receptor, type II 1,110263413 Down
*
0,04
Il20 Interleukin 20
0,02
Cytokine Receptors Il2rb Interleukin 2 receptor, beta chain 1,241338864 Down
0,00
Il2rg Interleukin 2 receptor, gamma chain 2,381319172 Down P53
Cortex Hipocamp Limbic Cerebellum
Cytokine Genes Il3 Interleukin 3 37,08474645 Up
Il4 Interleukin 4 3,367385754 Down
Wild type
Relative Densitometric Units
Cytokine Receptors Il5ra Interleukin 5 receptor, alpha 2,579592178 Down 0,60
HIF
Transgenic
Il6ra Interleukin 6 receptor, alpha 1,783400838 Down
0,50 HIF
Il6st Interleukin 6 signal transducer 1,439890398 Down
Il8rb Interleukin 8 receptor, beta 0,40
Cytokine Genes Itgam Integrin alpha M 1,000635124 Up
PPAR-γ
Itgb2 Integrin beta 2 2,014762802 Down 0,30
Lta Lymphotoxin A *
0,20
Ltb Lymphotoxin B 1,873029991 Down *
Mif Macrophage megration inhibitory factor 1,50753657 Down 0,10
Tubuline
Scye1 Small inducible cytokine subfamily E, member 1 2,60739291 Down
Spp1 Secreted phosphoprotein 1 12,42332116 Down 0,00
Tgfb1 Transforming growth factor, beta 1 2,89172027 Down Cortex Hipocamp Limbic Cerebellum
4,5 C H L Ce / C H L Ce
Tnf Tumor necrosis factor
PPAR-γ wild type transgenic
Tnfrsf1a Tumor necrosis factor receptor superfamily, member 1a 1,904976235 Down 4
Wild Type
Relative Densitometric Units
Tnfrsf1b Tumor necrosis factor receptor superfamily, member 1b 1,047576063 Down 3,5 Transgenic
Cd4Olg CD40 ligand 3
Tollip Toll interacting protein 2,123415944 Down 2,5
Xcr1 Chemokine (C motif) receptor 1
2
Gusb Glucuronidase, beta 2,889892846 Down
1,5
Hprt1 Hypoxantine guanine phosphoribosyl transferase 1 2,051438636 Down
1
Hsp90ab1 Heat shock protein 90 kDa alpha (cytosolic) class B 1 2,2017032 Down
Gapdh Glyceraldehyde-3-phosphate dehydrogenase 1 Down 0,5
Actb Actin, beta, cytoplasmic 1,736553671 Down 0
MGDC Mouse genomic DNA Contamination cortex hipocamp limbic cerebellum
Fig. 4.- Western-blot from 7th months cortex samples of female wild type and transgenic mice. Western-blot
Fig. 1.- Microarray from cortex samples, wild type vs transgenic (APP/Presenilin 1) mice. RNA determined different pro-inflammatory and anti-inflammatory mediators.
obtained from 7th months cortex samples of female wild type and transgenic mice. Microarray
determined different pro-inflammatory and anti-inflammatory mediators.
CONCLUSIONS
1. Microarray determined an induction of pro-inflammatory and reduction of anti-inflammatory mediators in transgenic APP/Presenilin 1 compared with wild type.
2. Pro-inflammatory proteins are increased and anti-inflammatory proteins are decreased in transgenic compared with wild type, such as Fig 1, 2 and 3 shown.
3. Fig. 4 shows induction of PPAR-γ in hippocampus, limbic system and cerebellum from 7th months of female transgenic compared wild type. HIF protein are decreased in transgenic compared willd type and also p-
53 shows a decreases values in transgenic mice compared with wild type.
4. Our study demonstrated and unbalance between inflammatory and anti-inflammatory mediators in transgenic APP/Presenilin 1 mice compared with wild type.