A. Hughes, DE Gottschling, An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast, Nature 492, 261–265 (13 December 2012), doi:10.1038/nature11654
Adam L. Hughes & Daniel E. Gottschling
Protein kinases are enzymes that phosphorylate other proteins and cause functional changes in target proteins. There are over 500 types of protein kinases in genomes that can modify about 30% of proteins. Protein kinase A, C, and G are three important protein kinases that are regulated by different mechanisms and have various functions in different cell types. Protein kinases play critical roles in many cellular processes and their dysregulation can lead to diseases like cancer.
The document summarizes a study that constructed a baculovirus-silkworm multigene expression system for producing virus-like particles. Key points:
- Researchers developed a new baculovirus vector using Bombyx mori nuclear polyhedrosis virus (BmNPV) that could simultaneously express multiple foreign genes in silkworm larvae.
- Using this system, they co-expressed three fluorescent proteins and three structural proteins from rotavirus in silkworms. Electron microscopy confirmed the structural proteins self-assembled into virus-like particles.
- The system efficiently produced high yields of functional multisubunit complexes and virus-like particles in silkworms at low cost
Pks associated with the cell survival and cell deathJayaPrakash369
Protein kinases are enzymes that add phosphate groups to proteins, changing their activity. They are involved in processes like signal transduction, cell differentiation, and cell proliferation. Several protein kinases play roles in regulating cell survival, proliferation, and apoptosis. CK2 protects cells from caspase-mediated apoptosis. WNK3 increases cell survival by blocking caspase-3 dependent apoptosis. AKT promotes cell survival by phosphorylating BAD and inhibiting apoptotic processes. DAPK1, DAPK2, and DAPK3 are protein kinases that regulate apoptosis and autophagy.
The complement system is part of the innate and adaptive immune system. It consists of plasma proteins that activate in a cascade amplification pathway. There are three complement activation pathways: classical, lectin-binding, and alternative. Activation leads to opsonization, inflammation, and cell lysis. Complement activation is tightly regulated to prevent damage to self tissues. Deficiencies in complement proteins result in increased susceptibility to certain infections.
The document discusses the complement system, which consists of over 30 proteins produced by the liver that function in the immune system but are not antibodies. It works as a cascade system where one activation triggers another in a chain reaction. Complement activation can lead to cell lysis and generation of inflammatory substances. It plays a role in defense against bacteria and in inflammatory and autoimmune diseases. There are three complement activation pathways: classical, alternative, and lectin. The classical pathway is antibody-dependent while the alternative and lectin pathways are antibody-independent. Complement activation results in opsonization, inflammation, clearance of immune complexes, and lysis of pathogen cells.
The complement system is a collection of soluble proteins and membrane receptors that function in host defense against microbes and inflammatory reactions. It consists of more than 20 proteins numbered C1 through C9. The complement system works through three pathways - classical, lectin, and alternative - that ultimately activate C3 and C5 convertases, cleaving C3 and C5 into fragments that opsonize pathogens, induce inflammation, and form the membrane attack complex to lyse microbes. Complement activation is tightly regulated by inhibitory proteins to prevent damage to host cells. Deficiencies in complement proteins can increase susceptibility to certain infections.
The JAK-STAT signaling pathway transmits signals from extracellular chemicals to the nucleus, activating transcription of target genes. It consists of a cell surface receptor, associated Janus kinases (JAKs), and signal transducers and activators of transcription (STATs). When a ligand binds the receptor, JAKs phosphorylate STATs, which form dimers and translocate to the nucleus to regulate gene expression. The Ras/MAPK pathway similarly relays signals from cell surface receptors via Ras, Raf, MEK, and MAPK proteins to influence transcription. Both pathways are tightly regulated and important for processes like cell growth, differentiation, and apoptosis, with dysregulation contributing to diseases.
Protein kinases are enzymes that phosphorylate other proteins and cause functional changes in target proteins. There are over 500 types of protein kinases in genomes that can modify about 30% of proteins. Protein kinase A, C, and G are three important protein kinases that are regulated by different mechanisms and have various functions in different cell types. Protein kinases play critical roles in many cellular processes and their dysregulation can lead to diseases like cancer.
The document summarizes a study that constructed a baculovirus-silkworm multigene expression system for producing virus-like particles. Key points:
- Researchers developed a new baculovirus vector using Bombyx mori nuclear polyhedrosis virus (BmNPV) that could simultaneously express multiple foreign genes in silkworm larvae.
- Using this system, they co-expressed three fluorescent proteins and three structural proteins from rotavirus in silkworms. Electron microscopy confirmed the structural proteins self-assembled into virus-like particles.
- The system efficiently produced high yields of functional multisubunit complexes and virus-like particles in silkworms at low cost
Pks associated with the cell survival and cell deathJayaPrakash369
Protein kinases are enzymes that add phosphate groups to proteins, changing their activity. They are involved in processes like signal transduction, cell differentiation, and cell proliferation. Several protein kinases play roles in regulating cell survival, proliferation, and apoptosis. CK2 protects cells from caspase-mediated apoptosis. WNK3 increases cell survival by blocking caspase-3 dependent apoptosis. AKT promotes cell survival by phosphorylating BAD and inhibiting apoptotic processes. DAPK1, DAPK2, and DAPK3 are protein kinases that regulate apoptosis and autophagy.
The complement system is part of the innate and adaptive immune system. It consists of plasma proteins that activate in a cascade amplification pathway. There are three complement activation pathways: classical, lectin-binding, and alternative. Activation leads to opsonization, inflammation, and cell lysis. Complement activation is tightly regulated to prevent damage to self tissues. Deficiencies in complement proteins result in increased susceptibility to certain infections.
The document discusses the complement system, which consists of over 30 proteins produced by the liver that function in the immune system but are not antibodies. It works as a cascade system where one activation triggers another in a chain reaction. Complement activation can lead to cell lysis and generation of inflammatory substances. It plays a role in defense against bacteria and in inflammatory and autoimmune diseases. There are three complement activation pathways: classical, alternative, and lectin. The classical pathway is antibody-dependent while the alternative and lectin pathways are antibody-independent. Complement activation results in opsonization, inflammation, clearance of immune complexes, and lysis of pathogen cells.
The complement system is a collection of soluble proteins and membrane receptors that function in host defense against microbes and inflammatory reactions. It consists of more than 20 proteins numbered C1 through C9. The complement system works through three pathways - classical, lectin, and alternative - that ultimately activate C3 and C5 convertases, cleaving C3 and C5 into fragments that opsonize pathogens, induce inflammation, and form the membrane attack complex to lyse microbes. Complement activation is tightly regulated by inhibitory proteins to prevent damage to host cells. Deficiencies in complement proteins can increase susceptibility to certain infections.
The JAK-STAT signaling pathway transmits signals from extracellular chemicals to the nucleus, activating transcription of target genes. It consists of a cell surface receptor, associated Janus kinases (JAKs), and signal transducers and activators of transcription (STATs). When a ligand binds the receptor, JAKs phosphorylate STATs, which form dimers and translocate to the nucleus to regulate gene expression. The Ras/MAPK pathway similarly relays signals from cell surface receptors via Ras, Raf, MEK, and MAPK proteins to influence transcription. Both pathways are tightly regulated and important for processes like cell growth, differentiation, and apoptosis, with dysregulation contributing to diseases.
Complement was discovered in 1894 and represents the lytic activity of fresh serum. It functions to enhance phagocytosis, attract and activate phagocytes, lyse bacteria and infected cells, and regulate antibody responses. The complement system includes the classical, lectin, and alternative pathways which involve a cascade of complement proteins that activate one another, resulting in the membrane attack complex that causes lysis of target cells. Complement activation must be tightly regulated to avoid damage to host cells.
This document provides an overview of protein kinase cascades. It begins with an introduction to protein kinases and their function in phosphorylating proteins and playing roles in cellular processes. It then discusses the classification of protein kinases based on the amino acid they phosphorylate. Next, it explains the basic mechanism of phosphorylation by protein kinases using ATP. It proceeds to describe protein kinase cascades where one kinase phosphorylates and activates the next in a chain. Examples of double phosphorylation and multi-layer perceptrons in cascades are illustrated. Finally, some biological examples of different types of protein kinases are mentioned before concluding with references.
Includes notes about Akt/Protein kinase B.Protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation).
Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration
This file also includes the types, \signalling pathways and inhibitors of protein kinase B.
1. The JAK-STAT pathway involves cytokine binding to receptors which activates JAK proteins, leading to phosphorylation of STAT proteins. Phosphorylated STATs form dimers and translocate to the nucleus to initiate gene transcription.
2. The pathway is regulated by PIAS, PTPs, and SOCS proteins. PIAS can add SUMO groups or recruit HDACs to inhibit STATs. PTPs remove phosphates to inhibit signaling. SOCS proteins form complexes that ubiquitinate proteins like JAKs and receptors to target them for degradation.
3. In rheumatoid arthritis, overactive JAK-STAT signaling leads to excessive inflammation. Approved drugs tofacitinib, ruxolit
The complement system is part of the innate immune system and consists of over 30 proteins. It was originally identified in the 1890s by Jules Bordet and Paul Ehrlich as a heat-labile component of serum that enhanced the ability of antibodies to kill bacteria. There are three complement activation pathways: the classical pathway which is initiated by antibody-antigen complexes, the lectin pathway which is activated by mannose-binding lectin, and the alternative pathway which is spontaneously activated by microbial surfaces. Complement activation results in opsonization, inflammation, and formation of the membrane attack complex to kill microbes. Deficiencies in specific complement components can increase susceptibility to certain infections.
Innate immune system is very important in case of fish. Complement system is the part of innate immune system. In this presentation there is a overview of the complement system.
The complement system is part of the immune system and consists of over 30 proteins produced by the liver. It kills microbes in three ways: opsonization, inflammation, and cytolysis. It works as a cascade system where the activation of one protein triggers the activation of others. There are two pathways - the classical pathway which relies on antibodies, and the alternative pathway which does not require antibodies. Both pathways result in the formation of the membrane attack complex that causes cell lysis.
Tyrosine kinases are enzymes that transfer phosphate groups from ATP to tyrosine residues on proteins. There are two main families of tyrosine kinases: receptor tyrosine kinases and non-receptor tyrosine kinases. Receptor tyrosine kinases are transmembrane receptors that transmit extracellular signals to intracellular pathways. Examples include receptors for epidermal growth factor, insulin, fibroblast growth factors, platelet-derived growth factor, nerve growth factor, ephrins, and vascular endothelial growth factor.
The complement system is a protective cascading system composed of 25 proteins that can be activated via the classical and alternative pathways, culminating in phagocytosis, lysis, and inflammation. It is present in normal sera and composed of complex protein networks. The classical pathway involves 9 proteins and the alternative pathway involves 13 proteins. Complement activation results in opsonization to enhance phagocytosis, attraction of phagocytes, lysis of bacteria and infected cells, and clearance of immune complexes and apoptotic cells. Deficiencies in specific complement components can increase susceptibility to certain infections due to impaired opsonization or membrane attack functions.
This document discusses metabolic engineering strategies to optimize microbial production of various compounds. It describes optimizing genetic and regulatory processes in cells to increase production of desired substances. Key strategies include mathematically modeling metabolic networks to identify rate-limiting steps, and then using pathway deletion, addition, or modification to redirect flux. Specific examples optimize yeast strains to utilize xylose for ethanol production by expressing xylose pathway genes from other organisms and overexpressing transketolase and transaldolase to increase flux through the pentose phosphate pathway. Another example engineers E. coli to increase hydrogen production by overexpressing glucose-6-phosphate dehydrogenase and fructose-1,6-bisphosphatase to activate the pentose phosphate pathway and gluconeogenesis
Proto-oncogenes are normal genes that can become oncogenes following mutations. They encode proteins involved in cell growth, proliferation, differentiation and apoptosis. Examples include HER2, Wnt, Myc, Ras and genes in the Ras signaling pathway. Mutations in proto-oncogenes convert them into oncogenes, driving uncontrolled cell growth and tumor development. Common mutations are point mutations, which result in overactive gene products by altering transcription or protein function. For example, point mutations in Ras genes are found in many cancers and keep the Ras protein constantly active.
Presentation is good for MBBS (undergraduate) class. Complement system includes normal serum proteins that augment the function of immune system. There are three possible paths through which complement system can proceed. then common path follows leading to the formation of MAC complex that causes bacterial cell lysis. Opsonisation, Viral neutralization, clearing of immune complexes, etc. are other functions of complement system. Important diseases are linked to abnormal regulation of immune system.
The complement system consists of approximately 20 proteins that are mainly synthesized by the liver and play an important role in innate immunity. It has three main effects: lysis of cells, generation of inflammatory mediators, and enhancement of phagocytosis. There are three pathways of complement activation: the classical, lectin, and alternative pathways. The classical pathway is part of acquired immunity and requires antigen-antibody complexes, while the lectin and alternative pathways are part of innate immunity and activate in response to microbial surfaces. Complement activation leads to opsonization and lysis of pathogens as well as inflammatory responses. The system is tightly regulated to prevent damage to host cells. Deficiencies in complement proteins predispose individuals to certain infections
The complement system is part of the innate immune system and circulates in an inactive form until needed. There are three pathways that activate it - classical, lectin, and alternative. All three involve a cascade of enzymes that amplify the immune response by eventually producing C3 convertase. This triggers effects like opsonization, lysis of pathogens through membrane attack complexes, chemotaxis of immune cells, and inflammation. Complement activation supports both innate and adaptive immunity through linking with antibody complexes.
Recombinant yeast technology at the cutting edge robust tools for both design...NavPrabh Sandhu Johal
Recombinant DNA technology is major DNA-based tool that has gained popular attention in the past decade. Significant advances in the development of new strains and vectors, improved techniques, and the commercial availability of these tools coupled with a better understanding of the biology of yeast species have led the recombinant yeast technology a robust tool for both designed catalysts and new biologicals. Yeast combines molecular genetic manipulations and growth characteristics of prokaryotic organisms together with the sub-cellular machinery for performing post-translational protein modifications (O and N- linked glycosylation, disulphide bond formation) and secretion of protein (Intracellularly or extracellularly). A large number of yeast hosts (Saccharomyces cerevisiae, Pichia pastoris, Hansenula polymorpha, Kluyveromyces lactis, Yarrowia lipolytica, etc) are available for heterologous protein expression. The methylotrophic yeast, Pichia species is the most highly developed one among a small group of alternative yeast species chosen for their perceived advantages over S. cerevisiae as a expression host for the generation of recombinant protein of commercial interest. Advantages of the system include the AOX1 promoter (alcohol oxidase) and other alternate promoters (GAP, FLD1, PEX8, and YPT1), with transcription characteristics that are useful for regulating heterologous protein expression.
Auxotrophic mutants (MutS and Mut+) and a new set of biosynthetic markers such as ADE1, ARG4 and URA 3 have been used successfully for better selection of transformed host. Protease deficient hosts and site specific integration of expression vectors into Pichia genome result into high expression of gene of interest. Additional features that are present in certain P. pastoris expression vectors serve as tools for specialized functions. The availability of the expression system as a commercially available kit (Invitrogen) extends the usefulness of system. Several different secretion signal sequences including the native secretion signal or secretion signal sequences from S. cerevisiae such as µ factor prepro peptide causes the protein to be secreted into the growth medium, which greatly facilitates subsequent protein purification. The P. pastoris expression platform is now well developed, as proven by multiple products used in human and veterinary medicine and in industry. A better understanding of secretion signals, glycosylation, and endogenous yeast proteases would be extremely helpful in developing and improving the yeast heterologous expression system.
This document summarizes information about phosphoinositide 3-kinase (PI 3-Kinase) and Rho kinase. It discusses the discovery of PI 3-Kinase, its classes and mechanisms. It describes the functions of PI 3-Kinase in processes like cell growth, proliferation and cancer. The document also provides information on Rho kinase, including its role in vascular smooth muscle contraction and pathogenesis. Experimental tools for studying Rho kinase and its role at the molecular and cellular level are outlined. Potential therapeutic targets of PI 3-Kinase and Rho kinase inhibitors are also mentioned.
This document presents ChainRank, a method to identify context-specific subnetworks from genome-wide interaction networks. ChainRank models information flow using chains of interactions between start and end nodes. It prioritizes chains based on node scores like expression variability and connectivity. Applying ChainRank to a COPD interaction network, the top chains found showed a 50% improvement in precision over random and enriched for known COPD pathways. Combining multiple node scores yielded even better results, demonstrating ChainRank's ability to identify meaningful subnetworks.
This document summarizes Dagmar Waltemath's presentation on model management for systems biology projects. It discusses the need for effective data management strategies due to the large, complex, and heterogeneous nature of systems biology data. It recommends using a data management plan, dedicated model management systems like FAIRDOMHub, standards for sharing data, publishing models in repositories, ensuring model quality, and tracking provenance. The goal is to make studies reproducible, valuable, and sustainable.
Complement was discovered in 1894 and represents the lytic activity of fresh serum. It functions to enhance phagocytosis, attract and activate phagocytes, lyse bacteria and infected cells, and regulate antibody responses. The complement system includes the classical, lectin, and alternative pathways which involve a cascade of complement proteins that activate one another, resulting in the membrane attack complex that causes lysis of target cells. Complement activation must be tightly regulated to avoid damage to host cells.
This document provides an overview of protein kinase cascades. It begins with an introduction to protein kinases and their function in phosphorylating proteins and playing roles in cellular processes. It then discusses the classification of protein kinases based on the amino acid they phosphorylate. Next, it explains the basic mechanism of phosphorylation by protein kinases using ATP. It proceeds to describe protein kinase cascades where one kinase phosphorylates and activates the next in a chain. Examples of double phosphorylation and multi-layer perceptrons in cascades are illustrated. Finally, some biological examples of different types of protein kinases are mentioned before concluding with references.
Includes notes about Akt/Protein kinase B.Protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation).
Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration
This file also includes the types, \signalling pathways and inhibitors of protein kinase B.
1. The JAK-STAT pathway involves cytokine binding to receptors which activates JAK proteins, leading to phosphorylation of STAT proteins. Phosphorylated STATs form dimers and translocate to the nucleus to initiate gene transcription.
2. The pathway is regulated by PIAS, PTPs, and SOCS proteins. PIAS can add SUMO groups or recruit HDACs to inhibit STATs. PTPs remove phosphates to inhibit signaling. SOCS proteins form complexes that ubiquitinate proteins like JAKs and receptors to target them for degradation.
3. In rheumatoid arthritis, overactive JAK-STAT signaling leads to excessive inflammation. Approved drugs tofacitinib, ruxolit
The complement system is part of the innate immune system and consists of over 30 proteins. It was originally identified in the 1890s by Jules Bordet and Paul Ehrlich as a heat-labile component of serum that enhanced the ability of antibodies to kill bacteria. There are three complement activation pathways: the classical pathway which is initiated by antibody-antigen complexes, the lectin pathway which is activated by mannose-binding lectin, and the alternative pathway which is spontaneously activated by microbial surfaces. Complement activation results in opsonization, inflammation, and formation of the membrane attack complex to kill microbes. Deficiencies in specific complement components can increase susceptibility to certain infections.
Innate immune system is very important in case of fish. Complement system is the part of innate immune system. In this presentation there is a overview of the complement system.
The complement system is part of the immune system and consists of over 30 proteins produced by the liver. It kills microbes in three ways: opsonization, inflammation, and cytolysis. It works as a cascade system where the activation of one protein triggers the activation of others. There are two pathways - the classical pathway which relies on antibodies, and the alternative pathway which does not require antibodies. Both pathways result in the formation of the membrane attack complex that causes cell lysis.
Tyrosine kinases are enzymes that transfer phosphate groups from ATP to tyrosine residues on proteins. There are two main families of tyrosine kinases: receptor tyrosine kinases and non-receptor tyrosine kinases. Receptor tyrosine kinases are transmembrane receptors that transmit extracellular signals to intracellular pathways. Examples include receptors for epidermal growth factor, insulin, fibroblast growth factors, platelet-derived growth factor, nerve growth factor, ephrins, and vascular endothelial growth factor.
The complement system is a protective cascading system composed of 25 proteins that can be activated via the classical and alternative pathways, culminating in phagocytosis, lysis, and inflammation. It is present in normal sera and composed of complex protein networks. The classical pathway involves 9 proteins and the alternative pathway involves 13 proteins. Complement activation results in opsonization to enhance phagocytosis, attraction of phagocytes, lysis of bacteria and infected cells, and clearance of immune complexes and apoptotic cells. Deficiencies in specific complement components can increase susceptibility to certain infections due to impaired opsonization or membrane attack functions.
This document discusses metabolic engineering strategies to optimize microbial production of various compounds. It describes optimizing genetic and regulatory processes in cells to increase production of desired substances. Key strategies include mathematically modeling metabolic networks to identify rate-limiting steps, and then using pathway deletion, addition, or modification to redirect flux. Specific examples optimize yeast strains to utilize xylose for ethanol production by expressing xylose pathway genes from other organisms and overexpressing transketolase and transaldolase to increase flux through the pentose phosphate pathway. Another example engineers E. coli to increase hydrogen production by overexpressing glucose-6-phosphate dehydrogenase and fructose-1,6-bisphosphatase to activate the pentose phosphate pathway and gluconeogenesis
Proto-oncogenes are normal genes that can become oncogenes following mutations. They encode proteins involved in cell growth, proliferation, differentiation and apoptosis. Examples include HER2, Wnt, Myc, Ras and genes in the Ras signaling pathway. Mutations in proto-oncogenes convert them into oncogenes, driving uncontrolled cell growth and tumor development. Common mutations are point mutations, which result in overactive gene products by altering transcription or protein function. For example, point mutations in Ras genes are found in many cancers and keep the Ras protein constantly active.
Presentation is good for MBBS (undergraduate) class. Complement system includes normal serum proteins that augment the function of immune system. There are three possible paths through which complement system can proceed. then common path follows leading to the formation of MAC complex that causes bacterial cell lysis. Opsonisation, Viral neutralization, clearing of immune complexes, etc. are other functions of complement system. Important diseases are linked to abnormal regulation of immune system.
The complement system consists of approximately 20 proteins that are mainly synthesized by the liver and play an important role in innate immunity. It has three main effects: lysis of cells, generation of inflammatory mediators, and enhancement of phagocytosis. There are three pathways of complement activation: the classical, lectin, and alternative pathways. The classical pathway is part of acquired immunity and requires antigen-antibody complexes, while the lectin and alternative pathways are part of innate immunity and activate in response to microbial surfaces. Complement activation leads to opsonization and lysis of pathogens as well as inflammatory responses. The system is tightly regulated to prevent damage to host cells. Deficiencies in complement proteins predispose individuals to certain infections
The complement system is part of the innate immune system and circulates in an inactive form until needed. There are three pathways that activate it - classical, lectin, and alternative. All three involve a cascade of enzymes that amplify the immune response by eventually producing C3 convertase. This triggers effects like opsonization, lysis of pathogens through membrane attack complexes, chemotaxis of immune cells, and inflammation. Complement activation supports both innate and adaptive immunity through linking with antibody complexes.
Recombinant yeast technology at the cutting edge robust tools for both design...NavPrabh Sandhu Johal
Recombinant DNA technology is major DNA-based tool that has gained popular attention in the past decade. Significant advances in the development of new strains and vectors, improved techniques, and the commercial availability of these tools coupled with a better understanding of the biology of yeast species have led the recombinant yeast technology a robust tool for both designed catalysts and new biologicals. Yeast combines molecular genetic manipulations and growth characteristics of prokaryotic organisms together with the sub-cellular machinery for performing post-translational protein modifications (O and N- linked glycosylation, disulphide bond formation) and secretion of protein (Intracellularly or extracellularly). A large number of yeast hosts (Saccharomyces cerevisiae, Pichia pastoris, Hansenula polymorpha, Kluyveromyces lactis, Yarrowia lipolytica, etc) are available for heterologous protein expression. The methylotrophic yeast, Pichia species is the most highly developed one among a small group of alternative yeast species chosen for their perceived advantages over S. cerevisiae as a expression host for the generation of recombinant protein of commercial interest. Advantages of the system include the AOX1 promoter (alcohol oxidase) and other alternate promoters (GAP, FLD1, PEX8, and YPT1), with transcription characteristics that are useful for regulating heterologous protein expression.
Auxotrophic mutants (MutS and Mut+) and a new set of biosynthetic markers such as ADE1, ARG4 and URA 3 have been used successfully for better selection of transformed host. Protease deficient hosts and site specific integration of expression vectors into Pichia genome result into high expression of gene of interest. Additional features that are present in certain P. pastoris expression vectors serve as tools for specialized functions. The availability of the expression system as a commercially available kit (Invitrogen) extends the usefulness of system. Several different secretion signal sequences including the native secretion signal or secretion signal sequences from S. cerevisiae such as µ factor prepro peptide causes the protein to be secreted into the growth medium, which greatly facilitates subsequent protein purification. The P. pastoris expression platform is now well developed, as proven by multiple products used in human and veterinary medicine and in industry. A better understanding of secretion signals, glycosylation, and endogenous yeast proteases would be extremely helpful in developing and improving the yeast heterologous expression system.
This document summarizes information about phosphoinositide 3-kinase (PI 3-Kinase) and Rho kinase. It discusses the discovery of PI 3-Kinase, its classes and mechanisms. It describes the functions of PI 3-Kinase in processes like cell growth, proliferation and cancer. The document also provides information on Rho kinase, including its role in vascular smooth muscle contraction and pathogenesis. Experimental tools for studying Rho kinase and its role at the molecular and cellular level are outlined. Potential therapeutic targets of PI 3-Kinase and Rho kinase inhibitors are also mentioned.
This document presents ChainRank, a method to identify context-specific subnetworks from genome-wide interaction networks. ChainRank models information flow using chains of interactions between start and end nodes. It prioritizes chains based on node scores like expression variability and connectivity. Applying ChainRank to a COPD interaction network, the top chains found showed a 50% improvement in precision over random and enriched for known COPD pathways. Combining multiple node scores yielded even better results, demonstrating ChainRank's ability to identify meaningful subnetworks.
This document summarizes Dagmar Waltemath's presentation on model management for systems biology projects. It discusses the need for effective data management strategies due to the large, complex, and heterogeneous nature of systems biology data. It recommends using a data management plan, dedicated model management systems like FAIRDOMHub, standards for sharing data, publishing models in repositories, ensuring model quality, and tracking provenance. The goal is to make studies reproducible, valuable, and sustainable.
A modeling workflow in systems biology: An overviewAnna Zhukova
A talk at the 1st RSGLux Congress, November 2016, Belval-University, Luxembourg.
In this talk we go though different steps of a typical modeling workflow, such as model inference, curation, simulation and analysis. We discuss tools and knowledgebases (model databases, ontologies) that can be used at each step, as well as the standards (e.g. SBML, SBGN) that permit us to encode models in a machine-readable format that can be exchanged between various tools, and facilitates model reuse.
Paulo Vilaça outlines his educational and professional background, starting with completing a BSc in Computer Science Engineering in 2007 and an MSc in Bioinformatics in 2009. In 2010, he co-founded SilicoLife with colleagues to design optimal cell factories using computer modeling. SilicoLife started as a garage startup and later moved to a business incubator park and then converted a house near the University of Minho, where it is currently located. The company uses genome-scale modeling to enable the design of microbial strains optimized for producing biofuels, chemicals, and biopolymers.
Learn how to use tools in systems biology to model metabolic interactions within microbial communities. The workshop will cover background in constrained based modeling and show applications of modelling single and multiple species.
Biggs, M. B., Medlock, G. L., Kolling, G. L. and Papin, J. A. (2015), Metabolic network modeling of microbial communities. WIREs Syst Biol Med, 7: 317–334. doi:10.1002/wsbm.1308
The vitamin E phosphate nucleoside prodrug (VEPNP) platform is designed to bypass two major mechanisms of tumor resistance to nucleosides: nucleoside transport and kinase downregulation. Testing showed that VEPNPs NUC050 and NUC024 were relatively unaffected by the presence of dipyridamole, an inhibitor of nucleoside transport, while the activity of gemcitabine decreased significantly. Further experiments found that NUC050 was able to deliver gemcitabine-monophosphate intracellularly in deoxycytidine kinase-deficient cells, bypassing this mechanism of resistance. A pilot study in mice found that NUC050 had a half-life 13.9 times longer
This presentation covers a general introduction to expression vector, its components, types, and its application. Then it covers some of the expression system with examples.
Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor
Complete study available in Free Radical Biology and Medicine. 2017 Sep;110:176-187.
doi: 10.1016/j.freeradbiomed.2017.06.006. Epub 2017 Jun 9.
The CCK-8 cell viability assay showed that wortmannin has a dose-dependent cytotoxic effect on DU-145 prostate cancer cells, with an IC50 of approximately 100 nM. Flow cytometry analysis of cells treated with 100 nM wortmannin found a decrease in single activation of the PI3K pathway, an increase in dual PI3K/MAPK pathway activation, and a small increase in MAPK pathway activation. Phase contrast images suggest the cells underwent apoptosis rather than lysis in response to wortmannin, as there was little cell debris present. These results indicate wortmannin affects signaling cross-talk in DU-145 cells and may increase apoptosis through impacts on the MAPK and dual PI3
This study examined the effect of linolenic acid concentration on the expression of fatty acid biosynthetic genes in female C57BL/6j mouse livers. Mice were fed either a soybean or cottonseed diet with different linolenic acid levels during gestation and lactation. Their offspring were sacrificed at 21 days, and liver gene expression was analyzed. The genes fatty acid synthase (Fasn), elongation of very long chain fatty acids family member 6 (Elovl6), and stearoyl-CoA desaturase-1 (Scd1) showed higher expression in pups from the soybean diet group, and expression of Elovl6 was statistically significant. The results suggest that
This document summarizes research on how the nematode C. elegans is affected by different bacterial diets, and the role of interspecies systems biology in understanding this. Studies found that a Comamonas bacterial diet caused different effects on C. elegans' development, fertility and lifespan compared to an E. coli diet. Further work identified vitamin B12 as a key metabolite produced at much higher levels by Comamonas that mimics the effects of this diet. Vitamin B12 was found to regulate C. elegans gene expression and accelerate development via the methionine/SAM cycle, while also mitigating toxicity from propionic acid, another metabolite affected by the bacterial diets. This research demonstrates how studying
This document summarizes information about microtubule inhibiting drugs. It discusses the history of these drugs, including that the first known compound to bind tubulin was colchicine. It also describes the two main types of microtubule inhibitors - stabilizing agents like taxanes and destabilizing agents like vinca alkaloids. Specific drugs from each class are explained in terms of their source, structure, mechanism of action, pharmacokinetics, and clinical applications.
This document discusses tracing the evolution of the human body through analyzing the chemical evolution of proteins and other molecules in the body over time. It notes that tracking changes in conserved proteins that control fundamental processes, like the Pax6 gene which regulates eye development, can reveal how closely related different organisms are. It recommends using the human arrestin protein sequence as an example, performing BLAST searches to find the arrestin sequence in the human genome and other organism genomes, then aligning the protein sequences to compare percentages and determine evolutionary relationships.
Mitochondria are double membranous organelle, the inner membrane is more larger than the outer one. For this reason the inner membrane of the mitochondria folds inside forming a special figure called creasteae. The inner mitochondrial membrane (IMM) contains the subunits for oxidative phosphorylation (OXPHOS). And this inner mitochondrial membrane coverd by a second membrane called the outer mitochondrial membrane (OMM). We called mitochondria as a power house of cell not only they generates ATP via oxidative phosphorylation they also take part in various biochemical pathways such as- pyrimidine and purine biosynthesis, heme biosynthesis, the regulation of N2 balance in urea cycle, gluconeogenesis, keton body production and fatty acid degradation and elongation. They also take part in cell signalling via regulating the protein-protein interaction or by regulating the cellular concentration of calcium ion(Ca2+) and reactive oxygen species(ROS).
During various biological diseasesmitochondrial morphology altered, as in the case when there is lack of nutrient in our body mitochondria combine together to share their nutrient and alo their DNA and ETC components to maintain their OXPHOS. But in case of high energy demand of a part of body mitochondria undergo division or called fission because they move rapidly than lager one (Zhao et al., 2013). Fission also occur in mitotic cell to share equal amount of mitochondria to the daughter cells. Many questions arise in mitochondrial dinamics but here I am going to answer a most doubtful question- Is mitochondrial dynamics play any role in tumorigenic process? Is any oncogenic signalling play crucial role in morphological alteration of mitochondria?
Lee Hartwell used temperature sensitive cell division cycle (cdc) mutants in the budding yeast Saccharomyces cerevisiae to develop a model of the eukaryotic cell cycle. He found that cdc28 is required early in the cell cycle before bud emergence and DNA replication, representing a commitment to a new cell division cycle called Start. Passing Start commits the cell to completing the entire cell cycle. Cyclin levels correlate with progression through the cell cycle, rising and falling at each stage. Work from Paul Nurse and Tim Hunt showed that cyclin and the maturation promoting factor (MPF) are conserved regulators of mitosis across species.
This document discusses novel solutions for recombinant protein expression in yeast. It summarizes that whole 2μm plasmids are very stable expression vectors in yeast. Significant variation exists between yeast strains in terms of secretion capacity, and strain engineering through chemical mutagenesis and selection can increase protein expression and control proteolysis. High levels of various recombinant proteins have been expressed intracellularly and secreted from yeast, including albumin fusions up to 8 g/L. Mitotically stable vector systems and optimization of yeast strains through mutagenesis allows improved productivity, control of post-translational modifications, and enhanced downstream processing.
1. The document reports on a study investigating the role of insulin signaling in pancreatic β cells using Cre-loxP mediated recombination to generate βIRKO mice lacking the insulin receptor in β cells.
2. Results showed βIRKO mice exhibited impaired glucose tolerance and insulin secretion compared to controls. Expression of genes CENP-A and PLK1 were decreased in βIRKO cells.
3. Further experiments demonstrated insulin stimulates FoxM1 binding to the CENP-A and PLK1 genes, and CENP-A expression is reduced in type 2 diabetes patient islets. Knockout of CENP-A in β cells decreased proliferation.
1. The document contains calculations and questions related to pharmacology, physiology, structures, and pharmaceutical topics.
2. Key concepts covered include enzyme kinetics, glomerular filtration rate calculation, central tendency measures, drug clearance, pharmacokinetics, drug metabolism, organ systems, electromagnetic waves, and pharmaceutical compounding.
3. Various questions test knowledge of drug dosage forms, routes of administration, stability considerations, sterilization methods, and pharmaceutical calculations.
Mitochondria are organelles found in plant cells that provide energy and regulate important metabolic processes. Plant mitochondrial genomes vary significantly in size but generally encode proteins involved in oxidative phosphorylation as well as rRNAs and tRNAs. These genomes often contain introns, open reading frames, and chloroplast DNA sequences. Mutations in mitochondrial DNA can impact plant development and cause cytoplasmic male sterility. Expression of chimeric mitochondrial genes is associated with some cases of male sterility. Studies examine the role of mitochondrial proteins like uncoupling proteins and alternative oxidases in conferring stress tolerance in plants. The WA352 mitochondrial gene is implicated in cytoplasmic male sterility in rice through interaction with the nuclear-encoded protein COX11.
This study compared the cytotoxicity and induction of genes encoding metabolic enzymes in cells exposed to different alkylated polycyclic aromatic hydrocarbons (PAHs). An SRB assay showed little cell death between exposures of 1uM naphthalene, 1uM dimethyl naphthalene, 1uM BAP, and the vehicle control, except for 5uM BAP. RT-PCR analysis found that 1uM BAP induced expression of CYP1A1 and CYP1B1 genes, but 1uM naphthalene and dimethyl naphthalene did not induce gene expression. Comparing responses to the parent naphthalene and dimethylated naphthalene,
Cell cycle checkpoints, apoptosis and cancerSurender Rawat
1. The document discusses various aspects of the cell cycle, including its key phases and regulating molecules. It notes that the cell cycle includes growth, DNA replication, chromosome separation, and cytokinesis.
2. Major regulatory molecules discussed include cyclins, CDKs, Rb protein, and checkpoints like START that ensure DNA damage is repaired before progression.
3. External factors like nutrients and growth signals regulate the cell cycle at transition points like the G1/S boundary through pathways involving cyclins, CDKs, and Rb.
This document discusses factors that can cause stress in dairy cows around calving and impact their health and milk production. It notes that the period from 3 weeks before to 3 weeks after calving is the most challenging as cows face metabolic, digestive, and calving stresses. Reduced dry matter intake pre-calving can predispose cows to health disorders post-calving. The document reviews biomarkers like non-esterified fatty acids and beta-hydroxybutyrate that can indicate negative energy balance and ketosis in cows during this transition period. It also examines the liver's role in ketone body production and clearance from the bloodstream when cows produce more fatty acids than can be utilized.
The document discusses a study on metalloproteases (MP), enzymes that shape the extracellular matrix. The researchers aim to control irregularities in MP activity by inhibiting the MP gene. They plan to obtain and sequence the MP gene from the Bornean orangutan (Pongo pygmaeus) to gain information on a global health issue. Their goals are to purify and sequence the MP gene, transform E. coli with the gene for expression, and perform protease detection assays.
This document discusses epithelial-mesenchymal transition (EMT) and its role in cancer metastasis. It summarizes findings from a study using a triple-transgenic mouse model of breast cancer metastasis that found: 1) Primary tumor cells disseminated and formed metastases while maintaining their epithelial phenotype, not undergoing EMT. 2) Inhibiting EMT with miR-200 had no effect on metastasis. 3) Non-EMT tumor cells were sensitive to chemotherapy, whereas mesenchymal cells were resistant. The study provides evidence that EMT may not be required for cancer metastasis in this model.
This document discusses biological networks such as metabolic, regulatory, signaling, and protein-protein interaction networks. It specifically focuses on metabolic networks, describing Recon 2 as a global reconstruction of the human metabolic network containing over 7,000 reactions and 2,000 genes. ReconMap is introduced as a Google Maps interface to visualize and interact with Recon 2 integrated with omics data and simulation results. The document then discusses Leigh Syndrome, a progressive neurodegenerative disorder, and how a gene-phenotype network map is being built to help provide accurate diagnoses for patients by combining the map with whole exome sequencing data and metabolic testing.
This document discusses comparing microbial communities to multicellular organisms. It explores whether microbial communities can be understood as multicellular organisms and vice versa. The document notes some similarities in their evolution of multicellularity, such as both utilizing spatial and temporal gradients to drive differentiation. However, it also outlines some key differences, such as differentiated microbes being more autonomous than differentiated eukaryotic cells. The document concludes that while microbial communities and multicellular organisms share some common patterns in their development, different modeling approaches may be needed to represent their differing levels of cellular dependencies and interactions.
This document summarizes research demonstrating that misfolded alpha-synuclein proteins associated with Multiple System Atrophy (MSA) can behave like prions and be transmitted between cells and laboratory mice. Brain homogenates from 14 MSA patients induced alpha-synuclein aggregation in cultured cells and caused neurological dysfunction in mice. Serial transmission between mice demonstrated replication of the MSA prions. The findings suggest MSA has prion-like properties and raises health concerns.
This study used predictive big data analytics to analyze data from the Parkinson's Progression Markers Initiative (PPMI) study. The study:
1) Aggregated and harmonized imaging, genetic, clinical, and demographic data from over 1,000 PPMI participants.
2) Used this complex dataset to test both model-based and model-free machine learning techniques for predicting Parkinson's disease versus healthy controls.
3) Found that combinations of clinical measures, demographics, genetics, and neuroimaging biomarkers provided the most accurate predictions, with classification improved after balancing cohorts.
The document discusses Nicola Bonzanni's career path in science, which began with challenging himself by pursuing an MSc in Computer Science and a PhD in Bioinformatics. As a post-doc, his monthly routine involved teaching, researching relevant literature, working on personal projects, providing bioinformatics support, and attending meetings and writing grants. Currently, his daily routine at ENPICOM involves business development, customer acquisition, meeting with clients, discussing strategy, managing social media, administration, and working on projects. The document emphasizes managing time, building a network, and finding one's passion.
This document outlines Magali Michaut's career path and experiences in computational biology. It discusses her education history, including completing her PhD in Paris and postdoctoral research in Toronto. It also outlines her current role leading genetic interaction network analysis in Amsterdam. Additionally, it emphasizes the importance of soft skills for scientists, such as communication, collaboration, and networking. It encourages developing these skills in order to advance one's career and maximize contributions to their field.
Statistical inference of regulatory networks fro circadian regulation
Dirk, H., & Marco, G. (2014). Statistical inference of regulatory networks for circadian regulation. Statistical Applications in Genetics and Molecular Biology. http://dx.doi.org/10.1515/sagmb-2013-0051
This document discusses current concepts in cancer mechanics research. It summarizes that mechanical forces play an important role in tumor growth and therapy. Solid stress within tumors is caused by growth and surrounding tissue, and fluid stress includes microvascular and interstitial fluid pressures. Mechanical forces can influence gene expression, proliferation, apoptosis, invasiveness and the extracellular matrix. Experimental platforms are needed to better control stiffness and study its interplay with tumor phenotype. Imaging techniques like elastography and atomic force microscopy can provide insights into biomechanics. Understanding mechanics is key to informing novel treatment approaches.
This document summarizes a review article on computational approaches to predict bacteriophage-host relationships using metagenomic data. The review assessed various in silico methods including abundance-based profiles, genetic homology, CRISPR sequences, exact matches, and oligonucleotide profiles on a benchmark dataset of 820 phages and 153 bacterial genomes. The best performing approaches were blast searches and exact sequence matches, which could correctly identify the host around 30-40% of the time. However, most methods could only predict the host to within 1-4 possible bacteria. The predictive power was limited by current knowledge and database gaps as well as the complex dynamics between phages and hosts in environmental communities.
- Microbial metabolites from the gut microbiome, especially butyrate, play an important role in modulating intestinal damage and graft-versus-host disease (GvHD) severity.
- In mice that underwent allogeneic stem cell transplantation, butyrate levels decreased significantly in intestinal epithelial cells, likely due to reduced butyrate transporter expression from inflammation.
- Restoring butyrate levels through intragastric gavage improved epithelial integrity, reduced GvHD severity and improved survival. Specific butyrate-producing bacteria were also associated with lower GvHD risk.
The document summarizes the African turquoise killifish as a new model organism for studying aging and age-related diseases. It has several advantages over traditional models like worms, flies, mice and zebrafish as it is a short-lived vertebrate with a lifespan of only a few months. Researchers have used killifish to model telomere attrition and genetic anticipation during aging by generating mutants with loss of telomerase activity or point mutations mimicking human diseases. The killifish provides a platform to study conserved aging genes and hallmarks of aging in a naturally short-lived vertebrate model.
This document discusses gene regulatory networks (GRNs) and their topology. It introduces concepts like nodes, edges, motifs, and robustness. The key points are:
1) GRNs have specific topologies that allow them to maintain function and recover from perturbations, due to selective pressure for stability.
2) Real transcriptional networks can be modeled as nodes representing genes and edges representing interactions like transcriptional regulation. However, they do not capture post-transcriptional regulations.
3) For a network to be stable, its qualitative topology should not depend on quantitative parameters like protein concentrations. Stability also depends on the presence of certain network motifs like feedback loops.
This document provides links to resources from pizza club including slides and materials available at http://rsg-luxembourg.iscbsc.org/. It also lists a site for identifying predatory open access publishers, a text mining tool for miRNA-gene regulation called miRTex, an interactive web tool called Heat*seq for comparing NGS experiments to public data, and a neural network web tool available at http://playground.tensorflow.org/.
This study identified genetic factors that modify the age of onset of Huntington's disease by conducting a genome-wide association study. They found two single nucleotide variants on chromosome 15 that either delayed or hastened age of onset by 6 or 1.4 years, respectively. A variant on chromosome 8 was also found that hastened onset by 1.6 years. Pathway analysis implicated genes involved in DNA handling and repair, such as MLH1, in modifying disease onset. This study demonstrates that age of onset in Huntington's disease is influenced by genetic modifiers.
This document summarizes research on microRNAs that confer radioresistance in glioblastoma. Four miRNAs (miR-1, miR-125a, miR-150, miR-425) were identified that limit apoptosis induced by radiation and activate DNA damage checkpoint factors without affecting repair. miR-1 and miR-125a expression is induced by TGF-β signaling. Inhibiting these miRNAs can neutralize radioresistance caused by TGF-β. The miRNAs are expressed in primary glioblastoma samples and targeting them may benefit patients by increasing radiosensitivity.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Unlocking the mysteries of reproduction: Exploring fecundity and gonadosomati...AbdullaAlAsif1
The pygmy halfbeak Dermogenys colletei, is known for its viviparous nature, this presents an intriguing case of relatively low fecundity, raising questions about potential compensatory reproductive strategies employed by this species. Our study delves into the examination of fecundity and the Gonadosomatic Index (GSI) in the Pygmy Halfbeak, D. colletei (Meisner, 2001), an intriguing viviparous fish indigenous to Sarawak, Borneo. We hypothesize that the Pygmy halfbeak, D. colletei, may exhibit unique reproductive adaptations to offset its low fecundity, thus enhancing its survival and fitness. To address this, we conducted a comprehensive study utilizing 28 mature female specimens of D. colletei, carefully measuring fecundity and GSI to shed light on the reproductive adaptations of this species. Our findings reveal that D. colletei indeed exhibits low fecundity, with a mean of 16.76 ± 2.01, and a mean GSI of 12.83 ± 1.27, providing crucial insights into the reproductive mechanisms at play in this species. These results underscore the existence of unique reproductive strategies in D. colletei, enabling its adaptation and persistence in Borneo's diverse aquatic ecosystems, and call for further ecological research to elucidate these mechanisms. This study lends to a better understanding of viviparous fish in Borneo and contributes to the broader field of aquatic ecology, enhancing our knowledge of species adaptations to unique ecological challenges.
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
2. 2
Saccharomyces cerevisiae (Budding yeast)
unicellular eukaryotic organism small genome comprising about 6000
genes, which has been completely
sequenced
molecular genetic tools
Cost effective model
Easy to manipulate
High throughput screening
31% of yeast gene has a human
homolog
3. 3
Introduction
S. cerevisiae
Aged yeast cells
- Mitochondria fragmentation
- Increase ROS
- Loss of mitochondrial DNA
AGEING
Chronological life span
Replicative life span
S. cerevisiae
4. 4
Introduction
S. cerevisiae
Aged yeast cells
- Mitochondria fragmentation
- Increase ROS
- Loss of mitochondrial DNA
AGEING
Chronological life span
Replicative life span
S. cerevisiae
Number of times an
individual cell divides
7. 7
Method: Mother enrichment program (MEP)
Daughter Cell
the transcription
factor Ace2
Sequester in the cytoplasm
Transported into the nucleus
8. 8
Method: Mother enrichment program (MEP)
Cre-
EBD78
SUMO-conjugating
enzyme
Activator of the
anaphase-promoting
complex (APC)
Arrest
in M-phase
9. 9
Results: Mitochondrial dysfunction in aged yeast
Calcofluor staining of
the bud scar
TOM70-GFP
Mitochondrial marker
Nr. Cell division
Characterization of age-associated mitochondrial phenotypes
10. 10
Results: Decreased of mitochondrial function
DiOC6 : ΔΨ-dependent mitochondrial
fluorescent dye
11. 11
Mitochondrial structure in young cells
250 genes1)
2) Overexpression of the 250 genes
MEP strain expressing Tom70-GFP
Delayed to the onset of altered mitochondrial
morphology in aged cells
12. 12
Results: VAM1 and VPH2
VAM1
VPH2
A Catalytic subunit of V-ATPase
V-ATPase assembly
V-ATPase : Acidification of the
vacuole
Overexpression of VMA suppressed
mitochondrial dysfunction in 93 %
Overexpression of VPH2 suppressed
mitochondrial dysfunction in 77 %
Suppression by VMA1 or VPH2 overexpression required V-ATPase activity
13. 13
Results: Vacuolar and mitochondrial function are linked
• Overexpression of VMA1 and
VPH2 increase both media and
maximal replicative lifespan.
14. 14
How vpH affects mitochondrial function?
vacuolar protein degradation?
Deletion of PEP4
No alteration of mitochondrial structure
15. 15
How vpH affects mitochondrial function?
Import of vacuolar metabolite?
Overexpression of vacuolar
importers
+
ConcA
ATV1 Neutral amino acid transporter
Prevent mitochondrial dysfunction
16. 16
Results: ATV1 prevents mitochondrial fragmentation
Overexpression of
ATV1
• Prevent alteration of mitochondrial structure
• No change in vacuolar acidification
17. 17
Results: ATV1 as aging modulator
Deletion of ATV1
Development of age-induced mitochondrial
dysfunction
Overexpression = Extending RLS
Deletion = Shortening of RLS
18. 18
Conclusion
o Yeast is a good model for aging
o Link between vacuolar pH and mitochondrial function
o Link between metabolite transport and aging
o Vacuole functionalion as aging modulator
o Reestablishment of acidification in the vacuole in the
daughter cells
Expression of the Cre recombinase is restricted by a daughter-specific promoter derived from SCW11 (PSCW11) (Figure 1A). Daughter-specific expression from PSCW11 is regulated by the transcription factor Ace2, which is asymmetrically distributed to daughter cell nuclei prior to cytokinesis
Cre activity is also post-transcriptionally regulated by fusion to the estradiol-binding domain (EBD) of the murine estrogen receptor (Cre-EBD78). The EBD sequesters the fusion protein in the cytoplasm until estradiol is introduced, at which point the fusion protein is transported into the nucleus where Cre can act upon its loxP DNA substrates
Mitochondria—which are
normally tubular—fragmented and ultimately aggregated in aged cells
(Fig. 1a). Mitochondrial fragmentation was present early in the ageing
process (86% of cells at 8 divisions), and progressed to large aggregates
and small fragments (93% of cells at 17 divisions) that persisted
throughout ageing (median lifespan of 28 divisions).
Mitochondrial membrane potential decreases in aged cells as indicated
by DiOC6 staining of aged cells expressing the mitochondrial outer membrane protein Tom70-
mCherry. c, Mitochondrial import is reduced in aged cells. Localization of mitochondrial matrix
marker preCox4-mCherry in aged cells that also express Tom70-GFP. pre-Cox4-mCherry is
localized to the cytoplasm in cells with reduced mitochondrial import.
dependent on the membrane potential for protein import, which is imported into mitochondria proportional to the MMP
Mitochondrial structure is regulated by 250 identified genes in
young cells
Vma1 is the catalytic subunit of
the peripheral-membrane-associated V1 sector of the V-ATPase14.
Vph2 is an endoplasmic-reticulum-localized integral membrane
protein required for V-ATPase assembly15. Overexpression of VMA1
or VPH2 from a high-copy promoter suppressed age-induced mitochondrial
dysfunction in 93% and 77% of aged cells, respectively (17 or
16 divisions) (Fig. 1b and Supplementary Fig. 3a). Importantly, suppression
by VMA1 or VPH2 overexpression required V-ATPase
activity, as treatment with the specific V-ATPase inhibitor concanamycin
A (concA)16 blocked their ability to produce normal, tubular
mitochondria (Fig. 1b and Supplementary Fig. 3a).
that resembled mitochondrial
phenotypes present in aged cells.
If reduced import of a particular amino acid or ion into the vacuole led
to mitochondrial dysfunction, then overexpressing the transporter
required for import of that metabolite into the vacuole might suppress
mitochondrial dysfunction in cells with a low vacuolar proton gradient.
To test this, we reduced the vacuolar proton gradient by treating
cells with low concentrations of concA, and measured mitochondrial
DYwith DiOC6 in cells overexpressing individual vacuolar amino acid
or ion transporters. Overexpressing most characterized V-ATPasedependent
vacuolar importers22–24 had no (NHX1, VBA1, VBA3) or little (VCX1, VBA2) effect on mitochondrial function. However, overexpressing
AVT1, a neutral amino acid transporter25, prevented mitochondrial
dysfunction in 60% of cells
If reduced import of a particular amino acid or ion into the vacuole led
to mitochondrial dysfunction, then overexpressing the transporter
required for import of that metabolite into the vacuole might suppress
mitochondrial dysfunction in cells with a low vacuolar proton gradient.
To test this, we reduced the vacuolar proton gradient by treating
cells with low concentrations of concA, and measured mitochondrial
DYwith DiOC6 in cells overexpressing individual vacuolar amino acid
or ion transporters. Overexpressing most characterized V-ATPasedependent
vacuolar importers22–24 had no (NHX1, VBA1, VBA3) or little (VCX1, VBA2) effect on mitochondrial function. However, overexpressing
AVT1, a neutral amino acid transporter25, prevented mitochondrial
dysfunction in 60% of cells