Science.gov

Sample records for adaptive response protein

  1. Protein phosphorylation and regulation of adaptive responses in bacteria.

    PubMed Central

    Stock, J B; Ninfa, A J; Stock, A M

    1989-01-01

    Bacteria continuously adapt to changes in their environment. Responses are largely controlled by signal transduction systems that contain two central enzymatic components, a protein kinase that uses adenosine triphosphate to phosphorylate itself at a histidine residue and a response regulator that accepts phosphoryl groups from the kinase. This conserved phosphotransfer chemistry is found in a wide range of bacterial species and operates in diverse systems to provide different regulatory outputs. The histidine kinases are frequently membrane receptor proteins that respond to environmental signals and phosphorylate response regulators that control transcription. Four specific regulatory systems are discussed in detail: chemotaxis in response to attractant and repellent stimuli (Che), regulation of gene expression in response to nitrogen deprivation (Ntr), control of the expression of enzymes and transport systems that assimilate phosphorus (Pho), and regulation of outer membrane porin expression in response to osmolarity and other culture conditions (Omp). Several additional systems are also examined, including systems that control complex developmental processes such as sporulation and fruiting-body formation, systems required for virulent infections of plant or animal host tissues, and systems that regulate transport and metabolism. Finally, an attempt is made to understand how cross-talk between parallel phosphotransfer pathways can provide a global regulatory curcuitry. PMID:2556636

  2. Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training.

    PubMed

    Trommelen, Jorn; van Loon, Luc J C

    2016-11-28

    Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates, and enhances the skeletal muscle adaptive response to prolonged resistance-type exercise training. As the adaptive response to a single bout of resistance exercise extends well beyond the first couple of hours of post-exercise recovery, recent studies have begun to investigate the impact of the timing and distribution of protein ingestion during more prolonged recovery periods. Recent work has shown that overnight muscle protein synthesis rates are restricted by the level of amino acid availability. Protein ingested prior to sleep is effectively digested and absorbed, and thereby stimulates muscle protein synthesis rates during overnight recovery. When applied during a prolonged period of resistance-type exercise training, protein supplementation prior to sleep can further augment gains in muscle mass and strength. Recent studies investigating the impact of pre-sleep protein ingestion suggest that at least 40 g of protein is required to display a robust increase in muscle protein synthesis rates throughout overnight sleep. Furthermore, prior exercise allows more of the pre-sleep protein-derived amino acids to be utilized for de novo muscle protein synthesis during sleep. In short, pre-sleep protein ingestion represents an effective dietary strategy to improve overnight muscle protein synthesis, thereby improving the skeletal muscle adaptive response to exercise training.

  3. Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training

    PubMed Central

    Trommelen, Jorn; van Loon, Luc J. C.

    2016-01-01

    Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates, and enhances the skeletal muscle adaptive response to prolonged resistance-type exercise training. As the adaptive response to a single bout of resistance exercise extends well beyond the first couple of hours of post-exercise recovery, recent studies have begun to investigate the impact of the timing and distribution of protein ingestion during more prolonged recovery periods. Recent work has shown that overnight muscle protein synthesis rates are restricted by the level of amino acid availability. Protein ingested prior to sleep is effectively digested and absorbed, and thereby stimulates muscle protein synthesis rates during overnight recovery. When applied during a prolonged period of resistance-type exercise training, protein supplementation prior to sleep can further augment gains in muscle mass and strength. Recent studies investigating the impact of pre-sleep protein ingestion suggest that at least 40 g of protein is required to display a robust increase in muscle protein synthesis rates throughout overnight sleep. Furthermore, prior exercise allows more of the pre-sleep protein-derived amino acids to be utilized for de novo muscle protein synthesis during sleep. In short, pre-sleep protein ingestion represents an effective dietary strategy to improve overnight muscle protein synthesis, thereby improving the skeletal muscle adaptive response to exercise training. PMID:27916799

  4. [Quasi-adaptive response to alkylating agents in Escherichia coli and Ada-protein functions].

    PubMed

    Vasil'eva, S V; Moshkovskaia, E Iu; Terekhov, A S; Mikoian, V D; Vanin, A F

    2008-01-01

    In 2005 we have described in exponentially growing E. coli cells a new fundamental genetic phenomenon,--quasi-adaptive response to alkylating compounds (quasi-Ada). Phenotypic expression of quasi-Ada is similar to the true Ada response. However, in contrast to the letter, it develops in the course of pretreatment of the cells by a sublethal dose of nonalkylating agent, an NO-containing dinitrosyl iron complex with glutathione (DNICglu). To reveal the mechanisms of quasi-adaptation and its association with the function of the Ada regulatory protein, here we used a unique property of dual gene expression regulation of aidB1 gene, a part of the Ada-regulon, namely its relative independence from Ada protein in anaerobic conditions. Based on the results of aidB1 gene expression analysis an EPR spectra of E. coli MV2176 cells (aidB1::lacZ) in aerobic and anaerobic conditions after the corresponding treatments, we conclude that the function and the spatial structure of meAda and [(Cys-)2Fe+(NO+)2]Ada are identical and thus the nitrosylated protein represents a regulator of the Ada regulon gene expression during quasi-adaptation development.

  5. MSG5, a novel protein phosphatase promotes adaptation to pheromone response in S. cerevisiae.

    PubMed Central

    Doi, K; Gartner, A; Ammerer, G; Errede, B; Shinkawa, H; Sugimoto, K; Matsumoto, K

    1994-01-01

    Pheromone-stimulated yeast cells and haploid gpa1 deletion mutants arrest their cell cycle in G1. Overexpression of a novel gene called MSG5 suppresses this inhibition of cell division. Loss of MSG5 function leads to a diminished adaptive response to pheromone. Genetic analysis indicates that MSG5 acts at a stage where the protein kinases STE7 and FUS3 function to transmit the pheromone-induced signal. Since loss of MSG5 function causes an increase in FUS3 enzyme activity but not STE7 activity, we propose that MSG5 impinges on the pathway at FUS3. Sequence analysis suggests that MSG5 encodes a protein tyrosine phosphatase. This is supported by the finding that recombinant MSG5 has phosphatase activity in vitro and is able to inactivate autophosphorylated FUS3. Thus MSG5 might stimulate recovery from pheromone by regulating the phosphorylation state of FUS3. Images PMID:8306972

  6. Plant natriuretic peptides induce proteins diagnostic for an adaptive response to stress

    PubMed Central

    Turek, Ilona; Marondedze, Claudius; Wheeler, Janet I.; Gehring, Chris; Irving, Helen R.

    2014-01-01

    In plants, structural and physiological evidence has suggested the presence of biologically active natriuretic peptides (PNPs). PNPs are secreted into the apoplast, are systemically mobile and elicit a range of responses signaling via cGMP. The PNP-dependent responses include tissue specific modifications of cation transport and changes in stomatal conductance and the photosynthetic rate. PNP also has a critical role in host defense responses. Surprisingly, PNP-homologs are produced by several plant pathogens during host colonization suppressing host defense responses. Here we show that a synthetic peptide representing the biologically active fragment of the Arabidopsis thaliana PNP (AtPNP-A) induces the production of reactive oxygen species in suspension-cultured A. thaliana (Col-0) cells. To identify proteins whose expression changes in an AtPNP-A dependent manner, we undertook a quantitative proteomic approach, employing tandem mass tag (TMT) labeling, to reveal temporal responses of suspension-cultured cells to 1 nM and 10 pM PNP at two different time-points post-treatment. Both concentrations yield a distinct differential proteome signature. Since only the higher (1 nM) concentration induces a ROS response, we conclude that the proteome response at the lower concentration reflects a ROS independent response. Furthermore, treatment with 1 nM PNP results in an over-representation of the gene ontology (GO) terms “oxidation-reduction process,” “translation” and “response to salt stress” and this is consistent with a role of AtPNP-A in the adaptation to environmental stress conditions. PMID:25505478

  7. Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

    SciTech Connect

    Hamill, Michael J.; Jost, Marco; Wong, Cintyu; Elliott, Sean J.; Drennan, Catherine L.

    2011-11-21

    The process known as 'adaptive response' allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 {+-} 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 {angstrom} resolution crystal structure in space group P3{sub 2} that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.

  8. A proteomic adaptation of small intestinal mucosa in response to dietary protein limitation

    PubMed Central

    Qin, Chunfu; Qiu, Kai; Sun, Wenjuan; Jiao, Ning; Zhang, Xin; Che, Lianqiang; Zhao, Haiyi; Shen, Hexiao; Yin, Jingdong

    2016-01-01

    Dietary protein limitation (PL) is not only beneficial to human health but also applied to minimize nitrogen excretion in livestock production. However, the impact of PL on intestinal physiology is largely unknown. In this study, we identified 5275 quantitative proteins using a porcine model in which pigs suffered PL. A total of 202 proteins |log2 fold-change| > 1 were taken as differentially expressed proteins and subjected to functional and pathway enrichment analysis to reveal proteomic alterations of the jejunal mucosa. Combining with the results of western blotting analysis, we found that protein/carbohydrate digestion, intestinal mucosal tight junction and cell adhesion molecules, and the immune response to foreign antigens were increased in the jejunal mucosa of the pigs upon PL. In contrast, amino acid transport, innate and auto immunity, as well as cell proliferation and apoptosis were reduced. In addition, the expression of functional proteins that involved in DNA replication, transcription and mRNA splicing as well as translation were altered in the jejunal mucosa in response to PL. Furthermore, PL may reduce amino acid transport and cell proliferation through the depression of mTOR pathway. This study provides new insights into the molecular mechanisms underlying the small intestinal response to PL. PMID:27841298

  9. ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load

    PubMed Central

    Petrova, Kseniya; Tomba, Giulia; Vendruscolo, Michele

    2012-01-01

    Gene expression programs that regulate the abundance of the chaperone BiP adapt the endoplasmic reticulum (ER) to unfolded protein load. However, such programs are slow compared with physiological fluctuations in secreted protein synthesis. While searching for mechanisms that fill this temporal gap in coping with ER stress, we found elevated levels of adenosine diphosphate (ADP)–ribosylated BiP in the inactive pancreas of fasted mice and a rapid decline in this modification in the active fed state. ADP ribosylation mapped to Arg470 and Arg492 in the substrate-binding domain of hamster BiP. Mutations that mimic the negative charge of ADP-ribose destabilized substrate binding and interfered with interdomain allosteric coupling, marking ADP ribosylation as a rapid posttranslational mechanism for reversible inactivation of BiP. A kinetic model showed that buffering fluctuations in unfolded protein load with a recruitable pool of inactive chaperone is an efficient strategy to minimize both aggregation and costly degradation of unfolded proteins. PMID:22869598

  10. Adaptive response modelling

    NASA Astrophysics Data System (ADS)

    Campa, Alessandro; Esposito, Giuseppe; Belli, Mauro

    Cellular response to radiation is often modified by a previous delivery of a small "priming" dose: a smaller amount of damage, defined by the end point being investigated, is observed, and for this reason the effect is called adaptive response. An improved understanding of this effect is essential (as much as for the case of the bystander effect) for a reliable radiation risk assessment when low dose irradiations are involved. Experiments on adaptive response have shown that there are a number of factors that strongly influence the occurrence (and the level) of the adaptation. In particular, priming doses and dose rates have to fall in defined ranges; the same is true for the time interval between the delivery of the small priming dose and the irradiation with the main, larger, dose (called in this case challenging dose). Different hypotheses can be formulated on the main mechanism(s) determining the adaptive response: an increased efficiency of DNA repair, an increased level of antioxidant enzymes, an alteration of cell cycle progression, a chromatin conformation change. An experimental clearcut evidence going definitely in the direction of one of these explanations is not yet available. Modelling can be done at different levels. Simple models, relating the amount of damage, through elementary differential equations, to the dose and dose rate experienced by the cell, are relatively easy to handle, and they can be modified to account for the priming irradiation. However, this can hardly be of decisive help in the explanation of the mechanisms, since each parameter of these models often incorporates in an effective way several cellular processes related to the response to radiation. In this presentation we show our attempts to describe adaptive response with models that explicitly contain, as a dynamical variable, the inducible adaptive agent. At a price of a more difficult treatment, this approach is probably more prone to give support to the experimental studies

  11. Redox stress proteins are involved in adaptation response of the hyperthermoacidophilic archaeon Sulfolobus solfataricus to nickel challenge

    PubMed Central

    Salzano, Anna M; Febbraio, Ferdinando; Farias, Tiziana; Cetrangolo, Giovanni P; Nucci, Roberto; Scaloni, Andrea; Manco, Giuseppe

    2007-01-01

    Background Exposure to nickel (Ni) and its chemical derivatives has been associated with severe health effects in human. On the contrary, poor knowledge has been acquired on target physiological processes or molecular mechanisms of this metal in model organisms, including Bacteria and Archaea. In this study, we describe an analysis focused at identifying proteins involved in the recovery of the archaeon Sulfolobus solfataricus strain MT4 from Ni-induced stress. Results To this purpose, Sulfolobus solfataricus was grown in the presence of the highest nickel sulphate concentration still allowing cells to survive; crude extracts from treated and untreated cells were compared at the proteome level by using a bi-dimensional chromatography approach. We identified several proteins specifically repressed or induced as result of Ni treatment. Observed up-regulated proteins were largely endowed with the ability to trigger recovery from oxidative and osmotic stress in other biological systems. It is noteworthy that most of the proteins induced following Ni treatment perform similar functions and a few have eukaryal homologue counterparts. Conclusion These findings suggest a series of preferential gene expression pathways activated in adaptation response to metal challenge. PMID:17692131

  12. cAMP-responsive element binding protein: a vital link in embryonic hormonal adaptation.

    PubMed

    Schindler, Maria; Fischer, Sünje; Thieme, René; Fischer, Bernd; Santos, Anne Navarrete

    2013-06-01

    The transcription factor cAMP responsive element-binding protein (CREB) and activating transcription factors (ATFs) are downstream components of the insulin/IGF cascade, playing crucial roles in maintaining cell viability and embryo survival. One of the CREB target genes is adiponectin, which acts synergistically with insulin. We have studied the CREB-ATF-adiponectin network in rabbit preimplantation development in vivo and in vitro. From the blastocyst stage onwards, CREB and ATF1, ATF3, and ATF4 are present with increasing expression for CREB, ATF1, and ATF3 during gastrulation and with a dominant expression in the embryoblast (EB). In vitro stimulation with insulin and IGF-I reduced CREB and ATF1 transcripts by approximately 50%, whereas CREB phosphorylation was increased. Activation of CREB was accompanied by subsequent reduction in adiponectin and adiponectin receptor (adipoR)1 expression. Under in vivo conditions of diabetes type 1, maternal adiponectin levels were up-regulated in serum and endometrium. Embryonic CREB expression was altered in a cell lineage-specific pattern. Although in EB cells CREB localization did not change, it was translocated from the nucleus into the cytosol in trophoblast (TB) cells. In TB, adiponectin expression was increased (diabetic 427.8 ± 59.3 pg/mL vs normoinsulinaemic 143.9 ± 26.5 pg/mL), whereas it was no longer measureable in the EB. Analysis of embryonic adipoRs showed an increased expression of adipoR1 and no changes in adipoR2 transcription. We conclude that the transcription factors CREB and ATFs vitally participate in embryo-maternal cross talk before implantation in a cell lineage-specific manner. Embryonic CREB/ATFs act as insulin/IGF sensors. Lack of insulin is compensated by a CREB-mediated adiponectin expression, which may maintain glucose uptake in blastocysts grown in diabetic mothers.

  13. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    SciTech Connect

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  14. Signal Regulatory Protein alpha (SIRPalpha)+ Cells in the Adaptive Response to ESAT-6/CFP-10 Protein of Tuberculous Mycobacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10(CFP-10) are co-secreted proteins of Mycobacterium tuberculosis complex mycobacteria (includes M. bovis, the zoonotic agent of bovine tuberculosis) involved in phagolysosome escape of the bacillus and, potentially, in the eff...

  15. Functional analysis of the group 4 late embryogenesis abundant proteins reveals their relevance in the adaptive response during water deficit in Arabidopsis.

    PubMed

    Olvera-Carrillo, Yadira; Campos, Francisco; Reyes, José Luis; Garciarrubio, Alejandro; Covarrubias, Alejandra A

    2010-09-01

    Late-Embryogenesis Abundant (LEA) proteins accumulate to high levels during the last stages of seed development, when desiccation tolerance is acquired, and in vegetative and reproductive tissues under water deficit, leading to the hypothesis that these proteins play a role in the adaptation of plants to this stress condition. In this work, we obtained the accumulation patterns of the Arabidopsis (Arabidopsis thaliana) group 4 LEA proteins during different developmental stages and plant organs in response to water deficit. We demonstrate that overexpression of a representative member of this group of proteins confers tolerance to severe drought in Arabidopsis plants. Moreover, we show that deficiency of LEA proteins in this group leads to susceptible phenotypes upon water limitation, during germination, or in mature plants after recovery from severe dehydration. Upon recovery from this stress condition, mutant plants showed a reduced number of floral and axillary buds when compared with wild-type plants. The lack of these proteins also correlates with a reduced seed production under optimal irrigation, supporting a role in fruit and/or seed development. A bioinformatic analysis of group 4 LEA proteins from many plant genera showed that there are two subgroups, originated through ancient gene duplication and a subsequent functional specialization. This study represents, to our knowledge, the first genetic evidence showing that one of the LEA protein groups is directly involved in the adaptive response of higher plants to water deficit, and it provides data indicating that the function of these proteins is not redundant to that of the other LEA proteins.

  16. Rice G-protein subunits qPE9-1 and RGB1 play distinct roles in abscisic acid responses and drought adaptation.

    PubMed

    Zhang, Dong-Ping; Zhou, Yong; Yin, Jian-Feng; Yan, Xue-Jiao; Lin, Sheng; Xu, Wei-Feng; Baluška, František; Wang, Yi-Ping; Xia, Yi-Ji; Liang, Guo-hua; Liang, Jian-Sheng

    2015-10-01

    Heterotrimeric GTP-binding protein (G-protein)-mediated abscisic acid (ABA) and drought-stress responses have been documented in numerous plant species. However, our understanding of the function of rice G-protein subunits in ABA signalling and drought tolerance is limited. In this study, the function of G-protein subunits in ABA response and drought resistance in rice plants was explored. It was found that the transcription level of qPE9-1 (rice Gγ subunit) gradually decreased with increasing ABA concentration and the lack of qPE9-1 showed an enhanced drought tolerance in rice plants. In contrast, mRNA levels of RGB1 (rice Gβ subunit) were significantly upregulated by ABA treatment and the lack of RGB1 led to reduced drought tolerance. Furthermore, the results suggested that qPE9-1 negatively regulates the ABA response by suppressing the expression of key transcription factors involved in ABA and stress responses, while RGB1 positively regulates ABA biosynthesis by upregulating NCED gene expression under both normal and drought stress conditions. Taken together, it is proposed that RGB1 is a positive regulator of the ABA response and drought adaption in rice plants, whereas qPE9-1 is modulated by RGB1 and functions as a negative regulator in the ABA-dependent drought-stress responses.

  17. Activation of protein kinase D1 in mast cells in response to innate, adaptive, and growth factor signals.

    PubMed

    Murphy, Thomas R; Legere, Henry J; Katz, Howard R

    2007-12-01

    Little is known about the serine/threonine kinase protein kinase D (PKD)1 in mast cells. We sought to define ligands that activate PKD1 in mast cells and to begin to address the contributions of this enzyme to mast cell activation induced by diverse agonists. Mouse bone marrow-derived mast cells (BMMC) contained both PKD1 mRNA and immunoreactive PKD1 protein. Activation of BMMC through TLR2, Kit, or FcepsilonRI with Pam(3)CSK(4) (palmitoyl-3-cysteine-serine-lysine-4), stem cell factor (SCF), and cross-linked IgE, respectively, induced activation of PKD1, as determined by immunochemical detection of autophosphorylation. Activation of PKD1 was inhibited by the combined PKD1 and protein kinase C (PKC) inhibitor Gö 6976 but not by broad-spectrum PKC inhibitors, including bisindolylmaleimide (Bim) I. Pam(3)CSK(4) and SCF also induced phosphorylation of heat shock protein 27, a known substrate of PKD1, which was also inhibited by Gö 6976 but not Bim I in BMMC. This pattern also extended to activation-induced increases in mRNA encoding the chemokine CCL2 (MCP-1) and release of the protein. In contrast, both pharmacologic agents inhibited exocytosis of beta-hexosaminidase induced by SCF or cross-linked IgE. Our findings establish that stimuli representing innate, adaptive, and growth factor pathways activate PKD1 in mast cells. In contrast with certain other cell types, activation of PKD1 in BMMC is largely independent of PKC activation. Furthermore, our findings also indicate that PKD1 preferentially influences transcription-dependent production of CCL2, whereas PKC predominantly regulates the rapid exocytosis of preformed secretory granule mediators.

  18. Translational control in the stress adaptive response of cancer cells: a novel role for the heat shock protein TRAP1

    PubMed Central

    Matassa, D S; Amoroso, M R; Agliarulo, I; Maddalena, F; Sisinni, L; Paladino, S; Romano, S; Romano, M F; Sagar, V; Loreni, F; Landriscina, M; Esposito, F

    2013-01-01

    TNF receptor-associated protein 1 (TRAP1), the main mitochondrial member of the heat shock protein (HSP) 90 family, is induced in most tumor types and is involved in the regulation of proteostasis in the mitochondria of tumor cells through the control of folding and stability of selective proteins, such as Cyclophilin D and Sorcin. Notably, we have recently demonstrated that TRAP1 also interacts with the regulatory protein particle TBP7 in the endoplasmic reticulum (ER), where it is involved in a further extra-mitochondrial quality control of nuclear-encoded mitochondrial proteins through the regulation of their ubiquitination/degradation. Here we show that TRAP1 is involved in the translational control of cancer cells through an attenuation of global protein synthesis, as evidenced by an inverse correlation between TRAP1 expression and ubiquitination/degradation of nascent stress-protective client proteins. This study demonstrates for the first time that TRAP1 is associated with ribosomes and with several translation factors in colon carcinoma cells and, remarkably, is found co-upregulated with some components of the translational apparatus (eIF4A, eIF4E, eEF1A and eEF1G) in human colorectal cancers, with potential new opportunities for therapeutic intervention in humans. Moreover, TRAP1 regulates the rate of protein synthesis through the eIF2α pathway either under basal conditions or under stress, favoring the activation of GCN2 and PERK kinases, with consequent phosphorylation of eIF2α and attenuation of cap-dependent translation. This enhances the synthesis of selective stress-responsive proteins, such as the transcription factor ATF4 and its downstream effectors BiP/Grp78, and the cystine antiporter system xCT, thereby providing protection against ER stress, oxidative damage and nutrient deprivation. Accordingly, TRAP1 silencing sensitizes cells to apoptosis induced by novel antitumoral drugs that inhibit cap-dependent translation, such as ribavirin or 4EGI

  19. Yeast hEST1A/B (SMG5/6)-like proteins contribute to environment-sensing adaptive gene expression responses.

    PubMed

    Lai, Xianning; Beilharz, Traude; Au, Wei-Chun; Hammet, Andrew; Preiss, Thomas; Basrai, Munira A; Heierhorst, Jörg

    2013-10-03

    During its natural life cycle, budding yeast (Saccharomyces cerevisiae) has to adapt to drastically changing environments, but how environmental-sensing pathways are linked to adaptive gene expression changes remains incompletely understood. Here, we describe two closely related yeast hEST1A-B (SMG5-6)-like proteins termed Esl1 and Esl2 that contain a 14-3-3-like domain and a putative PilT N-terminus ribonuclease domain. We found that, unlike their metazoan orthologs, Esl1 and Esl2 were not involved in nonsense-mediated mRNA decay or telomere maintenance pathways. However, in genome-wide expression array analyses, absence of Esl1 and Esl2 led to more than two-fold deregulation of ∼50 transcripts, most of which were expressed inversely to the appropriate metabolic response to environmental nutrient supply; for instance, normally glucose-repressed genes were derepressed in esl1Δ esl2Δ double mutants during growth in a high-glucose environment. Likewise, in a genome-wide synthetic gene array screen, esl1Δ esl2Δ double mutants were synthetic sick with null mutations for Rim8 and Dfg16, which form the environmental-sensing complex of the Rim101 pH response gene expression pathway. Overall, these results suggest that Esl1 and Esl2 contribute to the regulation of adaptive gene expression responses of environmental sensing pathways.

  20. Formation and Regulation of Adaptive Response in Nematode Caenorhabditis elegans

    PubMed Central

    Zhao, Y.-L.; Wang, D.-Y.

    2012-01-01

    All organisms respond to environmental stresses (e.g., heavy metal, heat, UV irradiation, hyperoxia, food limitation, etc.) with coordinated adjustments in order to deal with the consequences and/or injuries caused by the severe stress. The nematode Caenorhabditis elegans often exerts adaptive responses if preconditioned with low concentrations of agents or stressor. In C. elegans, three types of adaptive responses can be formed: hormesis, cross-adaptation, and dietary restriction. Several factors influence the formation of adaptive responses in nematodes, and some mechanisms can explain their response formation. In particular, antioxidation system, heat-shock proteins, metallothioneins, glutathione, signaling transduction, and metabolic signals may play important roles in regulating the formation of adaptive responses. In this paper, we summarize the published evidence demonstrating that several types of adaptive responses have converged in C. elegans and discussed some possible alternative theories explaining the adaptive response control. PMID:22997543

  1. Matricellular Proteins in Cardiac Adaptation and Disease

    PubMed Central

    Frangogiannis, Nikolaos G.

    2015-01-01

    The term “matricellular proteins” describes a family of structurally unrelated extracellular macromolecules that, unlike structural matrix proteins, do not play a primary role in tissue architecture, but are induced following injury and modulate cell:cell and cell:matrix interactions. When released to the matrix, matricellular proteins associate with growth factors, cytokines and other bioactive effectors and bind to cell surface receptors transducing signaling cascades. Matricellular proteins are upregulated in the injured and remodeling heart and play an important role in regulation of inflammatory, reparative, fibrotic and angiogenic pathways. Thrombospondins (TSP)-1, -2 and -4, tenascin-C and –X, secreted protein acidic and rich in cysteine (SPARC), osteopontin, periostin and members of the CCN family (including CCN1 and CCN2/Connective Tissue Growth Factor) are involved in a variety of cardiac pathophysiologic conditions, including myocardial infarction, cardiac hypertrophy and fibrosis, aging-associated myocardial remodeling, myocarditis, diabetic cardiomyopathy and valvular disease. This review manuscript discusses the properties and characteristics of the matricellular proteins and presents our current knowledge on their role in cardiac adaptation and disease. Understanding the role of matricellular proteins in myocardial pathophysiology and identification of the functional domains responsible for their actions may lead to design of peptides with therapeutic potential for patients with heart disease. PMID:22535894

  2. [Mechanism of cytogenetic adaptive response induced by low dose radiation].

    PubMed

    Cai, L; Liu, S

    1990-11-01

    Cytogenetic observation on human lymphocytes indicated that pre-exposure of 10, 50 and 75 mGy X-rays could induced the adaptive response. Experimental results with different temperature treatment showed that the adaptive response induced by low dose radiation could be enhanced by 41 degrees C and 43 degrees C, but inhibited by 4 degrees C in addition the treatment by 41 degrees C for one hour could also cause the adaptive response as did low dose radiation. Results showed that adaptive response induced by low dose radiation (10 or 50 mGy X-rays) could be eliminated by the protein synthesis inhibitor, implying that the adaptive response is related with the metabolism of cells, especially with the production of certain protective proteins.

  3. The adaptive immune response in celiac disease.

    PubMed

    Qiao, Shuo-Wang; Iversen, Rasmus; Ráki, Melinda; Sollid, Ludvig M

    2012-07-01

    Compared to other human leukocyte antigen (HLA)-associated diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, fundamental aspects of the pathogenesis in celiac disease are relatively well understood. This is mostly because the causative antigen in celiac disease-cereal gluten proteins-is known and the culprit HLA molecules are well defined. This has facilitated the dissection of the disease-relevant CD4+ T cells interacting with the disease-associated HLA molecules. In addition, celiac disease has distinct antibody responses to gluten and the autoantigen transglutaminase 2, which give strong handles to understand all sides of the adaptive immune response leading to disease. Here we review recent developments in the understanding of the role of T cells, B cells, and antigen-presenting cells in the pathogenic immune response of this instructive disorder.

  4. Adaptive Responses Limited by Intrinsic Noise.

    PubMed

    Shankar, Prabhat; Nishikawa, Masatoshi; Shibata, Tatsuo

    2015-01-01

    Sensory systems have mechanisms to respond to the external environment and adapt to them. Such adaptive responses are effective for a wide dynamic range of sensing and perception of temporal change in stimulus. However, noise generated by the adaptation system itself as well as extrinsic noise in sensory inputs may impose a limit on the ability of adaptation systems. The relation between response and noise is well understood for equilibrium systems in the form of fluctuation response relation. However, the relation for nonequilibrium systems, including adaptive systems, are poorly understood. Here, we systematically explore such a relation between response and fluctuation in adaptation systems. We study the two network motifs, incoherent feedforward loops (iFFL) and negative feedback loops (nFBL), that can achieve perfect adaptation. We find that the response magnitude in adaption systems is limited by its intrinsic noise, implying that higher response would have higher noise component as well. Comparing the relation of response and noise in iFFL and nFBL, we show that whereas iFFL exhibits adaptation over a wider parameter range, nFBL offers higher response to noise ratio than iFFL. We also identify the condition that yields the upper limit of response for both network motifs. These results may explain the reason of why nFBL seems to be more abundant in nature for the implementation of adaption systems.

  5. Adaptive Responses Limited by Intrinsic Noise

    PubMed Central

    Shankar, Prabhat; Nishikawa, Masatoshi; Shibata, Tatsuo

    2015-01-01

    Sensory systems have mechanisms to respond to the external environment and adapt to them. Such adaptive responses are effective for a wide dynamic range of sensing and perception of temporal change in stimulus. However, noise generated by the adaptation system itself as well as extrinsic noise in sensory inputs may impose a limit on the ability of adaptation systems. The relation between response and noise is well understood for equilibrium systems in the form of fluctuation response relation. However, the relation for nonequilibrium systems, including adaptive systems, are poorly understood. Here, we systematically explore such a relation between response and fluctuation in adaptation systems. We study the two network motifs, incoherent feedforward loops (iFFL) and negative feedback loops (nFBL), that can achieve perfect adaptation. We find that the response magnitude in adaption systems is limited by its intrinsic noise, implying that higher response would have higher noise component as well. Comparing the relation of response and noise in iFFL and nFBL, we show that whereas iFFL exhibits adaptation over a wider parameter range, nFBL offers higher response to noise ratio than iFFL. We also identify the condition that yields the upper limit of response for both network motifs. These results may explain the reason of why nFBL seems to be more abundant in nature for the implementation of adaption systems. PMID:26305221

  6. Bidirectional regulation of the cAMP response element binding protein encodes spatial map alignment in prism-adapting barn owls.

    PubMed

    Nichols, Grant S; DeBello, William M

    2008-10-01

    The barn owl midbrain contains mutually aligned maps of auditory and visual space. Throughout life, map alignment is maintained through the actions of an instructive signal that encodes the magnitude of auditory-visual mismatch. The intracellular signaling pathways activated by this signal are unknown. Here we tested the hypothesis that CREB (cAMP response element-binding protein) provides a cell-specific readout of instructive information. Owls were fitted with prismatic or control spectacles and provided rich auditory-visual experience: hunting live mice. CREB activation was analyzed within 30 min of hunting using phosphorylation state-specific CREB (pCREB) and CREB antibodies, confocal imaging, and immunofluorescence measurements at individual cell nuclei. In control owls or prism-adapted owls, which experience small instructive signals, the frequency distributions of pCREB/CREB values obtained for cell nuclei within the external nucleus of the inferior colliculus (ICX) were unimodal. In contrast, in owls adapting to prisms or readapting to normal conditions, the distributions were bimodal: certain cells had received a signal that positively regulated CREB and, by extension, transcription of CREB-dependent genes, whereas others received a signal that negatively regulated it. These changes were restricted to the subregion of the inferior colliculus that received optically displaced input, the rostral ICX, and were not evident in the caudal ICX or central nucleus. Finally, the topographic pattern of CREB regulation was patchy, not continuous, as expected from the actions of a topographically precise signal encoding discrete events. These results support a model in which the magnitude of CREB activation within individual cells provides a readout of the instructive signal that guides plasticity and learning.

  7. Adaptive acidification tolerance response of Salmonella typhimurium.

    PubMed

    Foster, J W; Hall, H K

    1990-02-01

    Salmonella typhimurium can encounter a wide variety of environments during its life cycle. One component of the environment which will fluctuate widely is pH. In nature, S. typhimurium can experience and survive dramatic acid stresses that occur in diverse ecological niches ranging from pond water to phagolysosomes. However, in vitro the organism is very sensitive to acid. To provide an explanation for how this organism survives acid in natural environments, the adaptive ability of S. typhimurium to become acid tolerant was tested. Logarithmically grown cells (pH 7.6) shifted to mild acid (pH 5.8) for one doubling as an adaptive procedure were 100 to 1,000 times more resistant to subsequent strong acid challenge (pH 3.3) than were unadapted cells shifted directly from pH 7.6 to 3.3. This acidification tolerance response required protein synthesis and appears to be a specific defense mechanism for acid. No cross protection was noted for hydrogen peroxide, SOS, or heat shock. Two-dimensional polyacrylamide gel electrophoretic analysis of acid-regulated polypeptides revealed 18 proteins with altered expression, 6 of which were repressed while 12 were induced by mild acid shifts. An avirulent phoP mutant was 1,000-fold more sensitive to acid than its virulent phoP+ parent, suggesting a correlation between acid tolerance and virulence. The Mg2(+)-dependent proton-translocating ATPase was also found to play an important role in acid tolerance. Mutants (unc) lacking this activity were unable to mount an acid tolerance response and were extremely acid sensitive. In contrast to these acid-sensitive mutants, a constitutively acid-tolerant mutant (atr) was isolated from wild-type LT2 after prolonged acid exposure. This mutant overexpressed several acidification tolerance response polypeptides. The data presented reveal an important acidification defense modulon with broad significance toward survival in biologically hostile environments.

  8. Oxidative stress, radiation-adaptive responses, and aging.

    PubMed

    Miura, Yuri

    2004-09-01

    Organisms living in an aerobic environment were forced to evolve effective cellular strategies to detoxify reactive oxygen species. Besides diverse antioxidant enzymes and compounds, DNA repair enzymes, and disassembly systems, which remove damaged proteins, regulation systems that control transcription, translation, and activation have also been developed. The adaptive responses, especially those to radiation, are defensive regulation mechanisms by which oxidative stress (conditioning irradiation) elicits a response against damage because of subsequent stress (challenging irradiation). Although many researchers have investigated these molecular mechanisms, they remain obscure because of their complex signaling pathways and the involvement of various proteins. This article reviews the factors concerned with radiation-adaptive response, the signaling pathways activated by conditioning irradiation, and the effects of aging on radiation-adaptive response. The proteomics approach is also introduced, which is a useful method for studying stress response in cells.

  9. Mitogen-activated protein kinase signal transduction and DNA repair network are involved in aluminum-induced DNA damage and adaptive response in root cells of Allium cepa L.

    PubMed Central

    Panda, Brahma B.; Achary, V. Mohan M.

    2014-01-01

    In the current study, we studied the role of signal transduction in aluminum (Al3+)-induced DNA damage and adaptive response in root cells of Allium cepa L. The root cells in planta were treated with Al3+ (800 μM) for 3 h without or with 2 h pre-treatment of inhibitors of mitogen-activated protein kinase (MAPK), and protein phosphatase. Also, root cells in planta were conditioned with Al3+ (10 μM) for 2 h and then subjected to genotoxic challenge of ethyl methane sulfonate (EMS; 5 mM) for 3 h without or with the pre-treatment of the aforementioned inhibitors as well as the inhibitors of translation, transcription, DNA replication and repair. At the end of treatments, roots cells were assayed for cell death and/or DNA damage. The results revealed that Al3+ (800 μM)-induced significant DNA damage and cell death. On the other hand, conditioning with low dose of Al3+ induced adaptive response conferring protection of root cells from genotoxic stress caused by EMS-challenge. Pre-treatment of roots cells with the chosen inhibitors prior to Al3+-conditioning prevented or reduced the adaptive response to EMS genotoxicity. The results of this study suggested the involvement of MAPK and DNA repair network underlying Al-induced DNA damage and adaptive response to genotoxic stress in root cells of A. cepa. PMID:24926302

  10. Plant Cell Adaptive Responses to Microgravity

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth; Kozeko, Liudmyla; Talalaev, Alexandr

    simulated microgravity and temperature elevation have different effects on the small HSP genes belonging to subfamilies with different subcellular localization: cytosol/nucleus - PsHSP17.1-СІІ and PsHSP18.1-СІ, cloroplasts - PsHSP26.2-Cl, endoplasmatic reticulum - PsHSP22.7-ER and mitochondria - PsHSP22.9-M: unlike high temperature, clinorotation does not cause denaturation of cell proteins, that confirms the sHSP chaperone function. Dynamics of investigated gene expression in pea seedlings growing 5 days after seed germination under clinorotation was similar to that in the stationary control. Similar patterns in dynamics of sHSP gene expression in the stationary control and under clinorotation may be one of mechanisms providing plant adaptation to simulated microgravity. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in cell organelle functional load. Thus, next certain changes in the structure and function of plant cells may be considered as adaptive: 1) an increase in the unsaturated fatty acid content in the plasmalemma, 2) rearrangements of organelle ultrastructure and an increase in their functional load, 3) an increase in cortical F-actin under destabilization of tubulin microtubules, 4) the level of gene expression and synthesis of heat shock proteins, 5) alterations of the enzyme and antioxidant system activity. The dynamics of these patterns demonstrated that the adaptation occurs on the principle of self-regulating systems in the limits of physiological norm reaction. The very importance of changed expression of genes involved in different cellular processes, especially HSP genes, in cell adaptation to altered gravity is discussed.

  11. Impaired Adaptive Response to Mechanical Overloading in Dystrophic Skeletal Muscle

    PubMed Central

    Joanne, Pierre; Hourdé, Christophe; Ochala, Julien; Caudéran, Yvain; Medja, Fadia; Vignaud, Alban; Mouisel, Etienne; Hadj-Said, Wahiba; Arandel, Ludovic; Garcia, Luis; Goyenvalle, Aurélie; Mounier, Rémi; Zibroba, Daria; Sakamato, Kei; Butler-Browne, Gillian; Agbulut, Onnik; Ferry, Arnaud

    2012-01-01

    Dystrophin contributes to force transmission and has a protein-scaffolding role for a variety of signaling complexes in skeletal muscle. In the present study, we tested the hypothesis that the muscle adaptive response following mechanical overloading (ML) would be decreased in MDX dystrophic muscle lacking dystrophin. We found that the gains in muscle maximal force production and fatigue resistance in response to ML were both reduced in MDX mice as compared to healthy mice. MDX muscle also exhibited decreased cellular and molecular muscle remodeling (hypertrophy and promotion of slower/oxidative fiber type) in response to ML, and altered intracellular signalings involved in muscle growth and maintenance (mTOR, myostatin, follistatin, AMPKα1, REDD1, atrogin-1, Bnip3). Moreover, dystrophin rescue via exon skipping restored the adaptive response to ML. Therefore our results demonstrate that the adaptive response in response to ML is impaired in dystrophic MDX muscle, most likely because of the dystrophin crucial role. PMID:22511986

  12. Protein cold adaptation: Role of physico-chemical parameters in adaptation of proteins to low temperatures.

    PubMed

    Shokrollahzade, Soheila; Sharifi, Fatemeh; Vaseghi, Akbar; Faridounnia, Maryam; Jahandideh, Samad

    2015-10-21

    During years 2007 and 2008, we published three papers (Jahandideh, 2007a, JTB, 246, 159-166; Jahandideh, 2007b, JTB, 248, 721-726; Jahandideh, 2008, JTB, 255, 113-118) investigating sequence and structural parameters in adaptation of proteins to low temperatures. Our studies revealed important features in cold-adaptation of proteins. Here, we calculate values of a new set of physico-chemical parameters and perform a comparative systematic analysis on a more comprehensive database of psychrophilic-mesophilic homologous protein pairs. Our obtained results confirm that psychrophilicity rules are not merely the inverse rules of thermostability; for instance, although contact order is reported as a key feature in thermostability, our results have shown no significant difference between contact orders of psychrophilic proteins compared to mesophilic proteins. We are optimistic that these findings would help future efforts to propose a strategy for designing cold-adapted proteins.

  13. Adaptive responses to antibody based therapy.

    PubMed

    Rodems, Tamara S; Iida, Mari; Brand, Toni M; Pearson, Hannah E; Orbuch, Rachel A; Flanigan, Bailey G; Wheeler, Deric L

    2016-02-01

    Receptor tyrosine kinases (RTKs) represent a large class of protein kinases that span the cellular membrane. There are 58 human RTKs identified which are grouped into 20 distinct families based upon their ligand binding, sequence homology and structure. They are controlled by ligand binding which activates intrinsic tyrosine-kinase activity. This activity leads to the phosphorylation of distinct tyrosines on the cytoplasmic tail, leading to the activation of cell signaling cascades. These signaling cascades ultimately regulate cellular proliferation, apoptosis, migration, survival and homeostasis of the cell. The vast majority of RTKs have been directly tied to the etiology and progression of cancer. Thus, using antibodies to target RTKs as a cancer therapeutic strategy has been intensely pursued. Although antibodies against the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have shown promise in the clinical arena, the development of both intrinsic and acquired resistance to antibody-based therapies is now well appreciated. In this review we provide an overview of the RTK family, the biology of EGFR and HER2, as well as an in-depth review of the adaptive responses undertaken by cells in response to antibody based therapies directed against these receptors. A greater understanding of these mechanisms and their relevance in human models will lead to molecular insights in overcoming and circumventing resistance to antibody based therapy.

  14. Adaptive tracking of narrowband HF channel response

    NASA Astrophysics Data System (ADS)

    Arikan, F.; Arikan, O.

    2003-12-01

    Estimation of channel impulse response constitutes a first step in computation of scattering function, channel equalization, elimination of multipath, and optimum detection and identification of transmitted signals through the HF channel. Due to spatial and temporal variations, HF channel impulse response has to be estimated adaptively. Based on developed state-space and measurement models, an adaptive Kalman filter is proposed to track the HF channel variation in time. Robust methods of initialization and adaptively adjusting the noise covariance in the system dynamics are proposed. In simulated examples under good, moderate and poor ionospheric conditions, it is observed that the adaptive Kalman filter based channel estimator provides reliable channel estimates and can track the variation of the channel in time with high accuracy.

  15. Adaptive immune responses to Candida albicans infection

    PubMed Central

    Richardson, Jonathan P; Moyes, David L

    2015-01-01

    Fungal infections are becoming increasingly prevalent in the human population and contribute to morbidity and mortality in healthy and immunocompromised individuals respectively. Candida albicans is the most commonly encountered fungal pathogen of humans, and is frequently found on the mucosal surfaces of the body. Host defense against C. albicans is dependent upon a finely tuned implementation of innate and adaptive immune responses, enabling the host to neutralise the invading fungus. Central to this protection are the adaptive Th1 and Th17 cellular responses, which are considered paramount to successful immune defense against C. albicans infections, and enable tissue homeostasis to be maintained in the presence of colonising fungi. This review will highlight the recent advances in our understanding of adaptive immunity to Candida albicans infections. PMID:25607781

  16. The role of 3D structure and protein conformation on the innate and adaptive immune responses to silk-based biomaterials.

    PubMed

    Bhattacharjee, Maumita; Schultz-Thater, Elke; Trella, Emanuele; Miot, Sylvie; Das, Sanskrita; Loparic, Marko; Ray, Alok R; Martin, Ivan; Spagnoli, Giulio C; Ghosh, Sourabh

    2013-11-01

    We have investigated monocyte and T cell responsiveness to silk based biomaterials of different physico-chemical characteristics. Here we report that untransformed CD14+ human monocytes respond to overnight exposure to silk fibroin-based biomaterials in tridimensional form by IL-1β and IL-6, but not IL-10 gene expression and protein production. In contrast, fibroin based materials in bidimensional form are unable to stimulate monocyte responsiveness. The elicitation of these effects critically requires contact between biomaterials and responding cells, is not sustained and becomes undetectable in longer term cultures. We also observed that NF-κβ and p38 MAP kinase play key roles in monocyte activation by silk-based biomaterials. On the other hand, fibroin based materials, irrespective of their physico-chemical characteristics appeared to be unable to induce the activation of peripheral blood T cells from healthy donors, as evaluated by the expression of activation markers and IFN-γ gene.

  17. Adaptive neural control of aeroelastic response

    NASA Astrophysics Data System (ADS)

    Lichtenwalner, Peter F.; Little, Gerald R.; Scott, Robert C.

    1996-05-01

    The Adaptive Neural Control of Aeroelastic Response (ANCAR) program is a joint research and development effort conducted by McDonnell Douglas Aerospace (MDA) and the National Aeronautics and Space Administration, Langley Research Center (NASA LaRC) under a Memorandum of Agreement (MOA). The purpose of the MOA is to cooperatively develop the smart structure technologies necessary for alleviating undesirable vibration and aeroelastic response associated with highly flexible structures. Adaptive control can reduce aeroelastic response associated with buffet and atmospheric turbulence, it can increase flutter margins, and it may be able to reduce response associated with nonlinear phenomenon like limit cycle oscillations. By reducing vibration levels and loads, aircraft structures can have lower acquisition cost, reduced maintenance, and extended lifetimes. Phase I of the ANCAR program involved development and demonstration of a neural network-based semi-adaptive flutter suppression system which used a neural network for scheduling control laws as a function of Mach number and dynamic pressure. This controller was tested along with a robust fixed-gain control law in NASA's Transonic Dynamics Tunnel (TDT) utilizing the Benchmark Active Controls Testing (BACT) wing. During Phase II, a fully adaptive on-line learning neural network control system has been developed for flutter suppression which will be tested in 1996. This paper presents the results of Phase I testing as well as the development progress of Phase II.

  18. Prostate cancer and the unfolded protein response

    PubMed Central

    Arnoldussen, Yke Jildouw; Saatcioglu, Fahri

    2016-01-01

    The endoplasmic reticulum (ER) is an essential organelle that contributes to several key cellular functions, including lipogenesis, gluconeogenesis, calcium storage, and organelle biogenesis. The ER also serves as the major site for protein folding and trafficking, especially in specialized secretory cells. Accumulation of misfolded proteins and failure of ER adaptive capacity activates the unfolded protein response (UPR) which has been implicated in several chronic diseases, including cancer. A number of recent studies have implicated UPR in prostate cancer (PCa) and greatly expanded our understanding of this key stress signaling pathway and its regulation in PCa. Here we summarize these developments and discuss their potential therapeutic implications. PMID:27303918

  19. Adaptive Responses to Tissue Injury: Role of Heme Oxygenase-1

    PubMed Central

    Agarwal, Anupam; Bolisetty, Subhashini

    2013-01-01

    Tissue injury may result as a consequence of a physical, chemical, or biological insult. Such injury recruits an adaptive response to restore homeostasis and protect against further injury. One of the most prompt protective and adaptive responses by all tissues is the robust activation of the highly inducible, anti-inflammatory, anti-oxidant, and anti-apoptotic protein, heme oxygenase-1 (HO-1). HO-1, a microsomal enzyme, catalyzes the breakdown of pro-oxidant heme, which is released from heme proteins to equimolar quantities of iron, carbon monoxide, and biliverdin. Biliverdin is converted to bilirubin by biliverdin reductase. The beneficial effects of HO-1 expression are not merely due to heme degradation but are also attributed to the cytoprotective properties of the byproducts of the reaction. Manipulation of this enzymatic system in a myriad of disease models has provided substantial evidence to support its role as a cytoprotective enzyme and is therefore an emerging therapeutic molecule. PMID:23874015

  20. Individual differences in response conflict adaptations

    PubMed Central

    Keye, Doris; Wilhelm, Oliver; Oberauer, Klaus; Stürmer, Birgit

    2013-01-01

    Conflict-monitoring theory argues for a general cognitive mechanism that monitors for conflicts in information-processing. If that mechanism detects conflict, it engages cognitive control to resolve it. A slow-down in response to incongruent trials (conflict effect), and a modulation of the conflict effect by the congruence of the preceding trial (Gratton or context effect) have been taken as indicators of such a monitoring system. The present study (N = 157) investigated individual differences in the conflict and the context effect in a horizontal and a vertical Simon task, and their correlation with working memory capacity (WMC). Strength of conflict was varied by proportion of congruent trials. Coherent factors could be formed representing individual differences in speeded performance, conflict adaptation, and context adaptation. Conflict and context factors were not associated with each other. Contrary to theories assuming a close relation between working memory and cognitive control, WMC showed no relation with any factors representing adaptation to conflict. PMID:24385971

  1. Green light signaling and adaptive response.

    PubMed

    Zhang, Tingting; Folta, Kevin M

    2012-01-01

    To a plant, the sun's light is not exclusively energy for photosynthesis, it also provides information about time and prevailing conditions. The plant's surroundings may dampen or filter solar energies, presenting plants with different spectral profiles of their light environment. Plants use this information to adjust form and physiology, tailoring gene expression to best match ambient conditions. Extensive literature exists on how blue, red and far-red light contribute to plant adaptive responses. A growing body of work identifies effects of green light (500-565 nm) that also shape plant biology. Green light responses are known to be either mediated through, or independent of, the cryptochrome blue light receptors. Responses to green light share a general tendency to oppose blue- or red-light-induced responses, including stem growth rate inhibition, anthocyanin accumulation and chloroplast gene expression. Recent evidence demonstrates a role for green light in sensing a shaded environment, independent from far-red shade responses.

  2. Phenotypical Temperature Adaptation of Protein Turnover in Desert Annuals 1

    PubMed Central

    Smrcka, Alan V.; Szarek, Stan R.

    1986-01-01

    Protein synthesis and protein degradation rates were measured in three desert annual species at four different experimental temperatures. The taxa chosen for this study were the C3 winter annuals, Bowlesia incana Ruiz & Pavon and Plantago insularis Eastw., and a C4 summer annual, Atriplex elegans (Moq.) D. Dietr. Peak rates of protein synthesis correlated well with the preferred habitat temperatures of B. incana and A. elegans; optima occurred at 25 and 35°C, respectively. Plants of P. insularis showed an optimum protein synthesis rate at 35°C; however, this optimum rate was considerably lower than for the other two species. Higher activation energies for protein synthesis tended to parallel adaptation to higher temperature habitats. Responses of protein degradation to temperature in A. elegans and B. incana were consistent with their natural thermal regimes, when evaluated for the transition from 25 to 35°C. Again, protein degradation in P. insularis shows an intermediate response to temperature during the 25 to 35°C transition. PMID:16664583

  3. Protein glycosylation as an adaptive response in Archaea: growth at different salt concentrations leads to alterations in Haloferax volcanii S-layer glycoprotein N-glycosylation.

    PubMed

    Guan, Ziqiang; Naparstek, Shai; Calo, Doron; Eichler, Jerry

    2012-03-01

    To cope with life in hypersaline environments, halophilic archaeal proteins are enriched in acidic amino acids. This strategy does not, however, offer a response to transient changes in salinity, as would post-translational modifications. To test this hypothesis, N-glycosylation of the Haloferax volcanii S-layer glycoprotein was compared in cells grown in high (3.4 M NaCl) and low (1.75 M NaCl) salt, as was the glycan bound to dolichol phosphate, the lipid upon which the N-linked glycan is assembled. In high salt, S-layer glycoprotein Asn-13 and Asn-83 are modified by a pentasaccharide, while dolichol phosphate is modified by a tetrasaccharide comprising the first four pentasaccharide residues. When the same targets were considered from cells grown in low salt, substantially less pentasaccharide was detected. At the same time, cells grown at low salinity contain dolichol phosphate modified by a distinct tetrasaccharide absent in cells grown at high salinity. The same tetrasaccharide modified S-layer glycoprotein Asn-498 in cells grown in low salt, whereas no glycan decorated this residue in cells grown in the high-salt medium. Thus, in response to changes in environmental salinity, Hfx. volcanii not only modulates the N-linked glycans decorating the S-layer glycoprotein but also the sites of such post-translational modification.

  4. The Adaptive Calibration Model of stress responsivity

    PubMed Central

    Ellis, Bruce J.; Shirtcliff, Elizabeth A.

    2010-01-01

    This paper presents the Adaptive Calibration Model (ACM), an evolutionary-developmental theory of individual differences in the functioning of the stress response system. The stress response system has three main biological functions: (1) to coordinate the organism’s allostatic response to physical and psychosocial challenges; (2) to encode and filter information about the organism’s social and physical environment, mediating the organism’s openness to environmental inputs; and (3) to regulate the organism’s physiology and behavior in a broad range of fitness-relevant areas including defensive behaviors, competitive risk-taking, learning, attachment, affiliation and reproductive functioning. The information encoded by the system during development feeds back on the long-term calibration of the system itself, resulting in adaptive patterns of responsivity and individual differences in behavior. Drawing on evolutionary life history theory, we build a model of the development of stress responsivity across life stages, describe four prototypical responsivity patterns, and discuss the emergence and meaning of sex differences. The ACM extends the theory of biological sensitivity to context (BSC) and provides an integrative framework for future research in the field. PMID:21145350

  5. Adaptive Evolution in Rodent Seminal Vesicle Secretion Proteins

    PubMed Central

    Clark, Nathaniel L.; Nguyen, Eric D.; Swanson, Willie J.

    2008-01-01

    Proteins involved in reproductive fitness have evolved unusually rapidly across diverse groups of organisms. These reproductive proteins show unusually high rates of amino acid substitutions, suggesting that the proteins have been subject to positive selection. We sought to identify seminal fluid proteins experiencing adaptive evolution because such proteins are often involved in sperm competition, host immunity to pathogens, and manipulation of female reproductive physiology and behavior. We performed an evolutionary screen of the mouse prostate transcriptome for genes with elevated evolutionary rates between mouse and rat. We observed that secreted rodent prostate proteins evolve approximately twice as fast as nonsecreted proteins, remarkably similar to findings in the primate prostate and in the Drosophila male accessory gland. Our screen led us to identify and characterize a group of seminal vesicle secretion (Svs) proteins and to show that the gene Svs7 is evolving very rapidly, with many amino acid sites under positive selection. Another gene in this group, Svs5, showed evidence of branch-specific selection in the rat. We also found that Svs7 is under selection in primates and, by using three-dimensional models, demonstrated that the same regions have been under selection in both groups. Svs7 has been identified as mouse caltrin, a protein involved in sperm capacitation, the process responsible for the timing of changes in sperm activity and behavior, following ejaculation. We propose that the most likely explanation of the adaptive evolution of Svs7 that we have observed in rodents and primates stems from an important function in sperm competition. PMID:18718917

  6. Adaptive immune responses to Acanthamoeba cysts.

    PubMed

    McClellan, Kathy; Howard, Kevin; Mayhew, Elizabeth; Niederkorn, Jerry; Alizadeh, Hassan

    2002-09-01

    Acanthamoeba cysts are not eliminated from the corneas of human subjects or experimentally infected animals. The persistence of Acanthamoeba cysts in the cornea indicates that either the cysts escape immunological elimination or are not recognized by the host's immunological elements. The aim of this study was to determine the immunogenicity and antigenicity of the Acanthamoeba cyst. Mice were immunized intraperitoneally and serum anti-Acanthamoeba IgG was measured by ELISA. Lymphoproliferative assay and delayed type hypersensitivity (DTH) responses to Acanthamoeba castellanii cyst and trophozoite antigens were used to determine the cell mediated immune responses against Acanthamoeba cysts. A. castellanii cysts were both immunogenic and antigenic, producing anti-Acanthamoeba serum IgG, T lymphocyte proliferation, and delayed type hypersensitivity responses. These results indicate that Acanthamoeba cysts are recognized by the immune system. The persistence of the organism in the human cornea means that these adaptive immune responses fail to kill Acanthamoeba cysts.

  7. Adaptive immune cells temper initial innate responses

    PubMed Central

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2008-01-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25−Foxp3− or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. PMID:17891146

  8. Adaptive immune cells temper initial innate responses.

    PubMed

    Kim, Kwang Dong; Zhao, Jie; Auh, Sogyong; Yang, Xuanming; Du, Peishuang; Tang, Hong; Fu, Yang-Xin

    2007-10-01

    Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1-deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25-Foxp3- or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.

  9. Resistance Training: Physiological Responses and Adaptations (Part 3 of 4).

    ERIC Educational Resources Information Center

    Fleck, Steven J.; Kraemer, William J.

    1988-01-01

    The physiological responses and adaptations which occur as a result of resistance training, such as cardiovascular responses, serum lipid count, body composition, and neural adaptations are discussed. Changes in the endocrine system are also described. (JL)

  10. Improving Adaptive Learning Technology through the Use of Response Times

    ERIC Educational Resources Information Center

    Mettler, Everett; Massey, Christine M.; Kellman, Philip J.

    2011-01-01

    Adaptive learning techniques have typically scheduled practice using learners' accuracy and item presentation history. We describe an adaptive learning system (Adaptive Response Time Based Sequencing--ARTS) that uses both accuracy and response time (RT) as direct inputs into sequencing. Response times are used to assess learning strength and…

  11. The Phage Shock Protein Response.

    PubMed

    Flores-Kim, Josué; Darwin, Andrew J

    2016-09-08

    The phage shock protein (Psp) system was identified as a response to phage infection in Escherichia coli, but rather than being a specific response to a phage, it detects and mitigates various problems that could increase inner-membrane (IM) permeability. Interest in the Psp system has increased significantly in recent years due to appreciation that Psp-like proteins are found in all three domains of life and because the bacterial Psp response has been linked to virulence and other important phenotypes. In this article, we summarize our current understanding of what the Psp system detects and how it detects it, how four core Psp proteins form a signal transduction cascade between the IM and the cytoplasm, and current ideas that explain how the Psp response keeps bacterial cells alive. Although recent studies have significantly improved our understanding of this system, it is an understanding that is still far from complete.

  12. Local adaptation in transgenerational responses to predators

    PubMed Central

    Walsh, Matthew R.; Castoe, Todd; Holmes, Julian; Packer, Michelle; Biles, Kelsey; Walsh, Melissa; Munch, Stephan B.; Post, David M.

    2016-01-01

    Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. ‘within-generation’ plasticity), such ‘transgenerational plasticity’ (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations. PMID:26817775

  13. Prophylaxis with a Respiratory Syncytial Virus (RSV) Anti-G Protein Monoclonal Antibody Shifts the Adaptive Immune Response to RSV rA2-line19F Infection from Th2 to Th1 in BALB/c Mice

    PubMed Central

    Boyoglu-Barnum, Seyhan; Chirkova, Tatiana; Todd, Sean O.; Barnum, Thomas R.; Gaston, Kelsey A.; Jorquera, Patricia; Haynes, Lia M.; Tripp, Ralph A.; Moore, Martin L.

    2014-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. In the present study, we investigated the effect of prophylactic treatment with the intact and F(ab′)2 forms of an anti-G protein monoclonal antibody (MAb), 131-2G, on the humoral and cellular adaptive immune responses to RSV rA2-line19F (r19F) challenge in BALB/c mice. The F(ab′)2 form of 131-2G does not decrease virus replication, but intact 131-2G does. The serum specimens for antibodies and spleen cells for memory T cell responses to RSV antigens were analyzed at 30, 45, 75, and 95 days postinfection (p.i.) with or without prior treatment with 131-2G. The ratios of Th2 to Th1 antibody isotypes at each time p.i indicated that both forms of MAb 131-2G shifted the subclass response from a Th2 (IgG1 and IgG2b) to a Th1 (IgG2A) bias. The ratio of IgG1 to IgG2A antibody titer was 3-fold to 10-fold higher for untreated than MAb-treated mice. There was also some increase in IgG (22% ± 13% increase) and neutralization (32% increase) in antibodies with MAb 131-2G prophylaxis at 75 days p.i. Treatment with 131-2G significantly (P ≤ 0.001) decreased the percentage of interleukin-4 (IL-4)-positive CD4 and CD8 cells in RSV-stimulated spleen cells at all times p.i., while the percentage of interferon gamma (IFN-γ) T cells significantly (P ≤ 0.001) increased ≥75 days p.i. The shift from a Th2- to a Th1-biased T cell response in treated compared to untreated mice likely was directed by the much higher levels of T-box transcription factor (T-bet) (≥45% versus <10%) in CD4 and CD8 T cells and lower levels of Gata-3 (≤2% versus ≥ 6%) in CD4 T cells in peptide-stimulated, day 75 p.i. spleen cells. These data show that the RSV G protein affects both humoral and cellular adaptive immune responses, and induction of 131-2G-like antibodies might improve the safety and

  14. Autophagy is an adaptive response in desmin-related cardiomyopathy

    PubMed Central

    Tannous, Paul; Zhu, Hongxin; Johnstone, Janet L.; Shelton, John M.; Rajasekaran, Namakkal S.; Benjamin, Ivor J.; Nguyen, Lan; Gerard, Robert D.; Levine, Beth; Rothermel, Beverly A.; Hill, Joseph A.

    2008-01-01

    A missense mutation in the αB-crystallin (CryAB) gene triggers a severe form of desmin-related cardiomyopathy (DRCM) characterized by accumulation of misfolded proteins. We hypothesized that autophagy increases in response to protein aggregates and that this autophagic activity is adaptive. Mutant CryAB (CryABR120G) triggered a >2-fold increase in cardiomyocyte autophagic activity, and blunting autophagy increased the rate of aggregate accumulation and the abundance of insoluble CryABR120G-associated aggregates. Cardiomyocyte-restricted overexpression of CryABR120G in mice induced intracellular aggregate accumulation and systolic heart failure by 12 months. As early as 2 months (well before the earliest declines in cardiac function), we detected robust autophagic activity. To test the functional significance of autophagic activation, we crossed CryABR120G mice with animals harboring heterozygous inactivation of beclin 1, a gene required for autophagy. Blunting autophagy in vivo dramatically hastened heart failure progression with a 3-fold increase in interstitial fibrosis, greater accumulation of polyubiquitinated proteins, larger and more extensive intracellular aggregates, accelerated ventricular dysfunction, and early mortality. This study reports activation of autophagy in DRCM. Further, our findings point to autophagy as an adaptive response in this proteotoxic form of heart disease. PMID:18621691

  15. Radio-Adaptive Responses of Mouse Myocardiocytes

    NASA Technical Reports Server (NTRS)

    Seawright, John W.; Westby, Christian M.

    2011-01-01

    One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) Cs-137 gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Pro-apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value . 0.003) 4hr after H, but not after 4hr LH when compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive

  16. Viruses are a dominant driver of protein adaptation in mammals

    PubMed Central

    Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

    2016-01-01

    Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001 PMID:27187613

  17. Adaptive immune response during hepatitis C virus infection.

    PubMed

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-04-07

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.

  18. Analysis of Unfolded Protein Response in Arabidopsis

    PubMed Central

    Chen, Yani; Brandizzi, Federica

    2014-01-01

    The unfolded protein response (UPR) is fundamental for development and adaption in eukaryotic cells. Arabidopsis has become one of the best model systems to uncover conserved mechanisms of the UPR in multicellular eukaryotes as well as organism-specific regulation of the UPR in plants. Monitoring the UPR in planta is an elemental approach to identifying regulatory components and to revealing molecular mechanisms of the plant UPR. In this chapter, we provide protocols for the induction and analyses of plant UPR at a molecular level in Arabidopsis. Three kinds of ER stress treatment methods and quantitation of the plant UPR activation are described here. PMID:23913037

  19. Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats

    PubMed Central

    Guttman, O; Baranovski, B M; Schuster, R; Kaner, Z; Freixo-Lima, G S; Bahar, N; Kalay, N; Mizrahi, M I; Brami, I; Ochayon, D E; Lewis, E C

    2015-01-01

    One would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acute-phase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity – ‘relative AAT deficiency’. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury. PMID:25351931

  20. Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats.

    PubMed

    Guttman, O; Baranovski, B M; Schuster, R; Kaner, Z; Freixo-Lima, G S; Bahar, N; Kalay, N; Mizrahi, M I; Brami, I; Ochayon, D E; Lewis, E C

    2015-02-01

    One would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acute-phase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity - 'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury.

  1. The adaptive response in radiobiology: evolving insights and implications.

    PubMed Central

    Wolff, S

    1998-01-01

    The first of the regularly reproducible experiments to show that very low doses of ionizing radiation, like very low doses of chemical agents, could induce mechanisms whereby cells become better fit to cope with subsequent exposures to high doses were carried out on the induction of chromosome aberrations in cultures of human lymphocytes. If cells that had been exposed to a very low dose (1 cGy) of X rays were subsequently exposed to a relatively high dose (1 Gy), approximately half as many chromosome breaks were induced. Subsequent experiments showed that this adaptive response to low doses requires a certain minimal dose before it becomes active; occurs only within a relatively small window of dose; is dose-rate dependent; and depends on the genetic constitution of the people or animals exposed, with some being unresponsive. It was further shown that the response to the low-dose preexposure was not instantaneous but took approximately 4 to 6 hr to become fully active, and could be prevented if during this period protein synthesis was inhibited, i.e., a necessary protein (enzyme) was being induced. In fact, subsequent experiments with two-dimensional gel electrophoresis showed new proteins in cells irradiated with 1 to 2 cGy. The adaptation induced by low doses of radiation was therefore attributed to the induction of a novel efficient chromosome break repair mechanism that if active at the time of challenge with high doses would lead to less residual damage. This hypothesis was strengthened by a series of experiments in which it was found that inhibitors of poly(ADP-ribose)polymerase, an enzyme implicated in DNA strand break rejoining, could prevent the adaptive response. Although the phenomenon is well established in cellular systems, it is still problematical as to whether or not it will have any utility in establishing risks of ionizing radiation to humans. Newer experiments have now been carried out on the mechanisms underlying the effect and whether or not

  2. Innate and Adaptive Immune Response to Fungal Products and Allergens.

    PubMed

    Williams, P Brock; Barnes, Charles S; Portnoy, Jay M

    2016-01-01

    Exposure to fungi and their products is practically ubiquitous, yet most of this is of little consequence to most healthy individuals. This is because there are a number of elaborate mechanisms to deal with these exposures. Most of these mechanisms are designed to recognize and neutralize such exposures. However, in understanding these mechanisms it has become clear that many of them overlap with our ability to respond to disruptions in tissue function caused by trauma or deterioration. These responses involve the innate and adaptive immune systems usually through the activation of nuclear factor kappa B and the production of cytokines that are considered inflammatory accompanied by other factors that can moderate these reactivities. Depending on different genetic backgrounds and the extent of activation of these mechanisms, various pathologies with resulting symptoms can ensue. Complicating this is the fact that these mechanisms can bias toward type 2 innate and adaptive immune responses. Thus, to understand what we refer to as allergens from fungal sources, we must first understand how they influence these innate mechanisms. In doing so it has become clear that many of the proteins that are described as fungal allergens are essentially homologues of our own proteins that signal or cause tissue disruptions.

  3. Melanoma and the Unfolded Protein Response

    PubMed Central

    Sykes, Erin K.; Mactier, Swetlana; Christopherson, Richard I.

    2016-01-01

    The UPR (unfolded protein response) has been identified as a key factor in the progression and metastasis of cancers, notably melanoma. Several mediators of the UPR are upregulated in cancers, e.g., high levels of GRP78 (glucose-regulator protein 78 kDa) correlate with progression and poor outcome in melanoma patients. The proliferative burden of cancer induces stress and activates several cellular stress responses. The UPR is a tightly orchestrated stress response that is activated upon the accumulation of unfolded proteins within the ER (endoplasmic reticulum). The UPR is designed to mediate two conflicting outcomtes, recovery and apoptosis. As a result, the UPR initiates a widespread signaling cascade to return the cell to homeostasis and failing to achieve cellular recovery, initiates UPR-induced apoptosis. There is evidence that ER stress and subsequently the UPR promote tumourigenesis and metastasis. The complete role of the UPR has yet to be defined. Understanding how the UPR allows for adaption to stress and thereby assists in cancer progression is important in defining an archetype of melanoma pathology. In addition, elucidation of the mechanisms of the UPR may lead to development of effective treatments of metastatic melanoma. PMID:26927180

  4. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    2005-09-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system’s search for antibodies, a balance has evolved between binding affinity and specificity.

  5. Linear ubiquitination signals in adaptive immune responses.

    PubMed

    Ikeda, Fumiyo

    2015-07-01

    Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways.

  6. Staphylococcus aureus surface proteins involved in adaptation to oxacillin identified using a novel cell shaving approach.

    PubMed

    Solis, Nestor; Parker, Benjamin L; Kwong, Stephen M; Robinson, Gareth; Firth, Neville; Cordwell, Stuart J

    2014-06-06

    Staphylococcus aureus is a Gram-positive pathogen responsible for a variety of infections, and some strains are resistant to virtually all classes of antibiotics. Cell shaving proteomics using a novel probability scoring algorithm to compare the surfaceomes of the methicillin-resistant, laboratory-adapted S. aureus COL strain with a COL strain in vitro adapted to high levels of oxacillin (APT). APT displayed altered cell morphology compared with COL and increased aggregation in biofilm assays. Increased resistance to β-lactam antibiotics was observed, but adaptation to oxacillin did not confer multidrug resistance. Analysis of the S. aureus COL and APT surfaceomes identified 150 proteins at a threshold determined by the scoring algorithm. Proteins unique to APT included the LytR-CpsA-Psr (LCP) domain-containing MsrR and SACOL2302. Quantitative RT-PCR showed increased expression of sacol2302 in APT grown with oxacillin (>6-fold compared with COL). Overexpression of sacol2302 in COL to levels consistent with APT (+ oxacillin) did not influence biofilm formation or β-lactam resistance. Proteomics using iTRAQ and LC-MS/MS identified 1323 proteins (∼50% of the theoretical S. aureus proteome), and cluster analysis demonstrated elevated APT abundances of LCP proteins, capsule and peptidoglycan biosynthesis proteins, and proteins involved in wall remodelling. Adaptation to oxacillin also induced urease proteins, which maintained culture pH compared to COL. These results show that S. aureus modifies surface architecture in response to antibiotic adaptation.

  7. Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

    PubMed Central

    O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

    2012-01-01

    An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

  8. Adaptive Resistance and Differential Protein Expression of Salmonella enterica Serovar Enteritidis Biofilms Exposed to Benzalkonium Chloride▿

    PubMed Central

    Mangalappalli-Illathu, Anil K.; Korber, Darren R.

    2006-01-01

    The development of adaptive resistance of Salmonella enterica serovar Enteritidis ATCC 4931 biofilms following exposure to benzalkonium chloride (BC) either continuously (1 μg ml−1) or intermittently (10 μg ml−1 for 10 min daily) was examined. Biofilms adapted to BC over a 144-h period could survive a normally lethal BC challenge (500 μg ml−1 for 10 min) and then regrow, as determined by increases in biofilm thickness, total biomass, and the ratio of the viable biomass to the nonviable biomass. Exposure of untreated control biofilms to the lethal BC challenge resulted in biofilm erosion and cell death. Proteins found to be up-regulated following BC adaptation were those involved in energy metabolism (TpiA and Eno), amino acid and protein biosynthesis (WrbA, TrxA, RplL, Tsf, Tuf, DsbA, and RpoZ), nutrient binding (FruB), adaptation (CspA), detoxification (Tpx, SodB, and a probable peroxidase), and degradation of 1,2-propanediol (PduJ and PduA). A putative universal stress protein (YnaF) was also found to be up-regulated. Proteins involved in proteolysis (DegQ), cell envelope formation (RfbH), adaptation (UspA), heat shock response (DnaK), and broad regulatory functions (Hns) were found to be down-regulated following adaptation. An overall increase in cellular protein biosynthesis was deduced from the significant up-regulation of ribosomal subunit proteins, translation elongation factors, and amino acid biosynthesis protein and down-regulation of serine endoprotease. The cold shock response, stress response, and detoxification are suggested to play roles in the adaptive resistance of Salmonella serovar Enteritidis biofilms to BC. PMID:16940079

  9. Adaptive resistance and differential protein expression of Salmonella enterica serovar Enteritidis biofilms exposed to benzalkonium chloride.

    PubMed

    Mangalappalli-Illathu, Anil K; Korber, Darren R

    2006-11-01

    The development of adaptive resistance of Salmonella enterica serovar Enteritidis ATCC 4931 biofilms following exposure to benzalkonium chloride (BC) either continuously (1 microg ml(-1)) or intermittently (10 microg ml(-1) for 10 min daily) was examined. Biofilms adapted to BC over a 144-h period could survive a normally lethal BC challenge (500 microg ml(-1) for 10 min) and then regrow, as determined by increases in biofilm thickness, total biomass, and the ratio of the viable biomass to the nonviable biomass. Exposure of untreated control biofilms to the lethal BC challenge resulted in biofilm erosion and cell death. Proteins found to be up-regulated following BC adaptation were those involved in energy metabolism (TpiA and Eno), amino acid and protein biosynthesis (WrbA, TrxA, RplL, Tsf, Tuf, DsbA, and RpoZ), nutrient binding (FruB), adaptation (CspA), detoxification (Tpx, SodB, and a probable peroxidase), and degradation of 1,2-propanediol (PduJ and PduA). A putative universal stress protein (YnaF) was also found to be up-regulated. Proteins involved in proteolysis (DegQ), cell envelope formation (RfbH), adaptation (UspA), heat shock response (DnaK), and broad regulatory functions (Hns) were found to be down-regulated following adaptation. An overall increase in cellular protein biosynthesis was deduced from the significant up-regulation of ribosomal subunit proteins, translation elongation factors, and amino acid biosynthesis protein and down-regulation of serine endoprotease. The cold shock response, stress response, and detoxification are suggested to play roles in the adaptive resistance of Salmonella serovar Enteritidis biofilms to BC.

  10. Determinants of immunogenic response to protein therapeutics.

    PubMed

    Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

    2012-09-01

    Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation.

  11. How Language Supports Adaptive Teaching through a Responsive Learning Culture

    ERIC Educational Resources Information Center

    Johnston, Peter; Dozier, Cheryl; Smit, Julie

    2016-01-01

    For students to learn optimally, teachers must design classrooms that are responsive to the full range of student development. The teacher must be adaptive, but so must each student and the learning culture itself. In other words, adaptive teaching means constructing a responsive learning culture that accommodates and even capitalizes on diversity…

  12. Emerging functions of the unfolded protein response in immunity

    PubMed Central

    Janssens, Sophie; Pulendran, Bali; Lambrecht, Bart N.

    2015-01-01

    The unfolded protein response (UPR) has traditionally been viewed as an adaptive response triggered upon accumulation of unfolded proteins in the endoplasmic reticulum (ER), aimed at restoring ER function. The UPR can also be an anticipatory response that is activated well before the disruption of protein homeostasis. UPR signaling intersects at many levels with the innate and adaptive immune response. In some immune cell types like dendritic cells and B cells, particular UPR sensors appear constitutively active in the absence of traditional UPR gene program induction, necessary for antigen presentation and immunoglobulin synthesis. The UPR also influences Toll-like receptor signaling and NF-κB activation, and some pathogens subvert the UPR. This review summarizes these emerging non-canonical functions of the UPR in immunity. PMID:25232821

  13. The role of adapter proteins in T cell activation.

    PubMed

    Koretzky, G A; Boerth, N J

    1999-12-01

    Engagement of antigen receptors on lymphocytes leads to a myriad of complex signal transduction cascades. Recently, work from several laboratories has led to the identification and characterization of novel adapter molecules, proteins with no intrinsic enzymatic activity but which integrate signal transduction pathways by mediating protein-protein interactions. Interestingly, it appears that many of these adapter proteins play as critical a role as the effector enzymes themselves in both lymphocyte development and activation. This review describes some of the biochemical and molecular features of several of these newly identified hematopoietic cell-specific adapter molecules highlighting their importance in regulating (both positively and negatively) signal transduction mediated by the T cell antigen receptor.

  14. Exercise training-induced gender-specific heat shock protein adaptations in human skeletal muscle.

    PubMed

    Morton, James P; Holloway, Kathryn; Woods, Paul; Cable, Nigel T; Burniston, Jatin; Evans, Louise; Kayani, Anna C; McArdle, Anne

    2009-02-01

    This study investigates the effects of short-term endurance training on heat shock protein (HSP) adaptations of male and female human skeletal muscle. The data demonstrate that females did not respond to continuous or interval training in terms of increasing HSP content of the vastus lateralis muscle. In contrast, males displayed HSP adaptations to both training interventions. These data provide a platform for future human studies to examine a potential gender-specific stress response to exercise.

  15. Time required for adaptation of protein metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animals that can appropriately adjust to varying environmental and nutritional conditions possess a survival advantage. Maintaining homeostasis and homeorhesis in response to changing nutritional conditions requires flexibility in nutrient partitioning and efficiencies. This is especially the case f...

  16. Light-adaptation in the photophobic response by Stentor coeruleus.

    PubMed

    Hong, C B; Prusti, R K; Song, P S

    1987-03-01

    Effects of preillumination on photophobic response (light-adaptation) and recovery of the photophobic sensitivity in the dark (dark-adaptation) in Stentor coeruleus were examined. When the cells were preilluminated with white light of 7.80 W/m2 for 2 min, the fluence-rate response curve of photophobic response was shifted toward higher light intensities by half an order of magnitude compared to the one without preillumination. Preillumination with a higher light intensity resulted in a further shift of the fluence-rate response curve. An action spectrum for light-adaptation showed a primary peak at 610 nm and secondary peaks at 540 and 480 nm which are almost identical to the peaks observed in the photophobic action spectrum. The light-adapted cells showed a recovery of their photophobic sensing ability following dark treatment. Dark-adaptation resulted in total recovery of photophobic sensing ability in 8 minutes for the most cases examined.

  17. Global transcriptional, physiological, and metabolite analyses of the responses of Desulfovibrio vulgaris hildenborough to salt adaptation.

    PubMed

    He, Zhili; Zhou, Aifen; Baidoo, Edward; He, Qiang; Joachimiak, Marcin P; Benke, Peter; Phan, Richard; Mukhopadhyay, Aindrila; Hemme, Christopher L; Huang, Katherine; Alm, Eric J; Fields, Matthew W; Wall, Judy; Stahl, David; Hazen, Terry C; Keasling, Jay D; Arkin, Adam P; Zhou, Jizhong

    2010-03-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by performing physiological, global transcriptional, and metabolite analyses. Salt adaptation was reflected by increased expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). The expression of genes involved in carbon metabolism, cell growth, and phage structures was decreased. Transcriptome profiles of D. vulgaris responses to salt adaptation were compared with transcriptome profiles of D. vulgaris responses to salt shock (short-term NaCl exposure). Metabolite assays showed that glutamate and alanine accumulated under salt adaptation conditions, suggesting that these amino acids may be used as osmoprotectants in D. vulgaris. Addition of amino acids (glutamate, alanine, and tryptophan) or yeast extract to the growth medium relieved salt-related growth inhibition. A conceptual model that links the observed results to currently available knowledge is proposed to increase our understanding of the mechanisms of D. vulgaris adaptation to elevated NaCl levels.

  18. A Sharing Item Response Theory Model for Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Segall, Daniel O.

    2004-01-01

    A new sharing item response theory (SIRT) model is presented that explicitly models the effects of sharing item content between informants and test takers. This model is used to construct adaptive item selection and scoring rules that provide increased precision and reduced score gains in instances where sharing occurs. The adaptive item selection…

  19. Responsiveness-to-Intervention: A "Systems" Approach to Instructional Adaptation

    ERIC Educational Resources Information Center

    Fuchs, Douglas; Fuchs, Lynn S.

    2016-01-01

    Classroom research on adaptive teaching indicates few teachers modify instruction for at-risk students in a manner that benefits them. Responsiveness-To-Intervention, with its tiers of increasingly intensive instruction, represents an alternative approach to adaptive instruction that may prove more workable in today's schools.

  20. Cold shock response and adaptation at near-freezing temperature in microorganisms.

    PubMed

    Inouye, Masayori; Phadtare, Sangita

    2004-06-09

    Microorganisms that naturally encounter sharp temperature shifts must develop strategies for responding and adapting to these shifts. Escherichia coli, which are adapted to living at both warm temperatures inside animals and cooler ambient temperatures, respond to low temperatures (10 degrees to 15 degrees C) by adjusting membrane lipid composition and increasing the production of proteins that act as "RNA chaperones" required for transcription and translation and proteins that facilitate ribosomal assembly. In contrast, yeast, which are adapted to cooler temperatures, show a relatively minor cold shock response after temperature shifts from 30 degrees to 10 degrees C but respond with a dramatic increase in the synthesis of trehalose and a heat shock protein when exposed to freezing or near-freezing temperatures. This emphasizes the fact that different groups of microorganisms exhibit distinct types of cold shock responses.

  1. Exposure to stressful environments - Strategy of adaptive responses

    NASA Technical Reports Server (NTRS)

    Farhi, Leon E.

    1991-01-01

    Stresses such as hypoxia, water lack, and heat exposure can produce strains in more than a single organ system, in turn stimulating the body to adapt in multiple ways. Nevertheless, a general strategy of the various adaptive responses emerges when the challenges are divided into three groups: (1) conditions that affect the supply of essential molecules, (2) stresses that prevent the body from regulating properly the output of waste products such as CO2 and heat, and (3) environments that disrupt body transport systems. Problems may arise when there is a conflict between two stresses requiring conflicting adaptive changes. An alternative to adaptation, creation of microenvironment, is often favored by the animal.

  2. Dietary protein requirements and adaptive advantages in athletes.

    PubMed

    Phillips, Stuart M

    2012-08-01

    Dietary guidelines from a variety of sources are generally congruent that an adequate dietary protein intake for persons over the age of 19 is between 0·8-0·9 g protein/kg body weight/d. According to the US/Canadian Dietary Reference Intakes, the RDA for protein of 0·8 g protein/kg/d is "...the average daily intake level that is sufficient to meet the nutrient requirement of nearly all [~98 %]… healthy individuals..." The panel also states that "...no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise." These recommendations are in contrast to recommendations from the US and Canadian Dietetic Association: "Protein recommendations for endurance and strength trained athletes range from 1·2 to 1·7 g/kg/d." The disparity between those setting dietary protein requirements and those who might be considered to be making practical recommendations for athletes is substantial. This may reflect a situation where an adaptive advantage of protein intakes higher than recommended protein requirements exists. That population protein requirements are still based on nitrogen balance may also be a point of contention since achieving balanced nitrogen intake and excretion likely means little to an athlete who has the primary goal of exercise performance. The goal of the present review is to critically analyse evidence from both acute and chronic dietary protein-based studies in which athletic performance, or correlates thereof, have been measured. An attempt will be made to distinguish between protein requirements set by data from nitrogen balance studies, and a potential adaptive 'advantage' for athletes of dietary protein in excess of the RDA.

  3. Multiple species of Bacillus subtilis DNA alkyltransferase involved in the adaptive response to simple alkylating agents

    SciTech Connect

    Morohoshi, F.; Munakata, N.

    1987-02-01

    Three molecular species of methyl-accepting proteins exist in Bacillus subtilis cells, which collect methyl groups from methylated DNA. A 20-kilodalton (kDa) protein was constitutively present in the cells of the ada/sup +/ (proficient in adaptive response) strain as well as in those of six ada (deficient in adaptive response) mutant strains and was assigned to the O/sup 6/-methylguanine:DNA methyltransferase. Another species of O/sup 6/-methylguanine:DNA methyltransferase, which had a molecular size of 22 kDa, emerged after adaptive treatment of the ada/sup +/ but not any of the ada mutant cells. A 27-kDa methyl-accepting protein, which preferred methylated poly(dT) to methylated calf thymus DNA as a substrate, was assigned to the methylphosphotriester:DNA methyltransferase. It was produced, after adaptive treatment, in the cells of ada/sup +/, ada-3, ada-4, and ada-6 strains but not in the cells of ada-1, ada-2, or ada-5 strains. These results support and extend the authors proposition that ada mutants can be classified into two groups; one (the ada-4 group) is defective only in the inducible synthesis of O/sup 6/-methylguanine:DNA methyltransferase (22-kDa protein), and the other (the ada-1 group) is deficient in the adaptive response in toto.

  4. An Adaptable Investigative Graduate Laboratory Course for Teaching Protein Purification

    ERIC Educational Resources Information Center

    Carroll, Christopher W.; Keller, Lani C.

    2014-01-01

    This adaptable graduate laboratory course on protein purification offers students the opportunity to explore a wide range of techniques while allowing the instructor the freedom to incorporate their own personal research interests. The course design involves two sequential purification schemes performed in a single semester. The first part…

  5. Global transcriptional, physiological and metabolite analyses of Desulfovibrio vulgaris Hildenborough responses to salt adaptation

    SciTech Connect

    He, Z.; Zhou, A.; Baidoo, E.; He, Q.; Joachimiak, M. P.; Benke, P.; Phan, R.; Mukhopadhyay, A.; Hemme, C.L.; Huang, K.; Alm, E.J.; Fields, M.W.; Wall, J.; Stahl, D.; Hazen, T.C.; Keasling, J.D.; Arkin, A.P.; Zhou, J.

    2009-12-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by physiological, global transcriptional, and metabolite analyses. The growth of D. vulgaris was inhibited by high levels of NaCl, and the growth inhibition could be relieved by the addition of exogenous amino acids (e.g., glutamate, alanine, tryptophan) or yeast extract. Salt adaptation induced the expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). Genes involved in carbon metabolism, cell motility, and phage structures were repressed. Comparison of transcriptomic profiles of D. vulgaris responses to salt adaptation with those of salt shock (short-term NaCl exposure) showed some similarity as well as a significant difference. Metabolite assays showed that glutamate and alanine were accumulated under salt adaptation, suggesting that they may be used as osmoprotectants in D. vulgaris. A conceptual model is proposed to link the observed results to currently available knowledge for further understanding the mechanisms of D. vulgaris adaptation to elevated NaCl.

  6. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  7. Adaptation in protein fitness landscapes is facilitated by indirect paths

    PubMed Central

    Wu, Nicholas C; Dai, Lei; Olson, C Anders; Lloyd-Smith, James O; Sun, Ren

    2016-01-01

    The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20L) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 204 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. DOI: http://dx.doi.org/10.7554/eLife.16965.001 PMID:27391790

  8. Proteomic insights into adaptive responses of Saccharomyces cerevisiae to the repeated vacuum fermentation.

    PubMed

    Cheng, Jing-Sheng; Zhou, Xiao; Ding, Ming-Zhu; Yuan, Ying-Jin

    2009-07-01

    The responses and adaptation mechanisms of the industrial Saccharomyces cerevisiae to vacuum fermentation were explored using proteomic approach. After qualitative and quantitative analyses, a total of 106 spots corresponding to 68 different proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differentially expressed proteins were involved in amino acid and carbohydrate metabolisms, various signal pathways (Ras/MAPK, Ras-cyclic adenosine monophosphate, and HOG pathway), and heat shock and oxidative responses. Among them, alternations in levels of 17 proteins associated with carbohydrate metabolisms, in particular, the upregulations of proteins involved in glycolysis, trehalose biosynthesis, and the pentose phosphate pathway, suggested vacuum-induced redistribution of the metabolic fluxes. The upregulation of 17 heat stress and oxidative response proteins indicated that multifactors contributed to oxidative stresses by affecting cell redox homeostasis. Taken together with upregulation in 14-3-3 proteins levels, 22 proteins were detected in multispots, respectively, indicating that vacuum might have promoted posttranslational modifications of some proteins in S. cerevisiae. Further investigation revealed that the elevations of the differentially expressed proteins were mainly derived from vacuum stress rather than the absence of oxygen. These findings provide new molecular mechanisms for understanding of adaptation and tolerance of yeast to vacuum fermentation.

  9. Adaptation responses in C4 photosynthesis of maize under salinity.

    PubMed

    Omoto, Eiji; Taniguchi, Mitsutaka; Miyake, Hiroshi

    2012-03-15

    The effect of salinity on C(4) photosynthesis was examined in leaves of maize, a NADP-malic enzyme (NADP-ME) type C(4) species. Potted plants with the fourth leaf blade fully developed were treated with 3% NaCl solution for 5d. Under salt treatment, the activities of pyruvate orthophosphate dikinase (PPDK), phosphoenolpyruvate carboxylase (PEPCase), NADP-dependent malate dehydrogenase (NADP-MDH) and NAD-dependent malate dehydrogenase (NAD-MDH), which are derived mainly from mesophyll cells, increased, whereas those of NADP-ME and ribulose-1,5-bisphosphate carboxylase, which are derived mainly from bundle sheath cells (BSCs), decreased. Immunocytochemical studies by electron microscopy revealed that PPDK protein increased, while the content of ribulose-1,5-bisphosphate carboxylase/oxygenase protein decreased under salinity. In salt-treated plants, the photosynthetic metabolites malate, pyruvate and starch decreased by 40, 89 and 81%, respectively. Gas-exchange analysis revealed that the net photosynthetic rate, the transpiration rate, stomatal conductance (g(s)) and the intercellular CO(2) concentration decreased strongly in salt-treated plants. The carbon isotope ratio (δ(13)C) in these plants was significantly lower than that in control. These findings suggest that the decrease in photosynthetic metabolites under salinity was induced by a reduction in gas-exchange. Moreover, in addition to the decrease in g(s), the decrease in enzyme activities in BSCs was responsible for the decline of C(4) photosynthesis. The increase of PPDK, PEPCase, NADP-MDH, and NAD-MDH activities and the decrease of NADP-ME activity are interpreted as adaptation responses to salinity.

  10. Secretome analysis revealed adaptive and non-adaptive responses of the Staphylococcus carnosus femB mutant.

    PubMed

    Nega, Mulugeta; Dube, Linda; Kull, Melanie; Ziebandt, Anne-Kathrin; Ebner, Patrick; Albrecht, Dirk; Krismer, Bernhard; Rosenstein, Ralf; Hecker, Michael; Götz, Friedrich

    2015-04-01

    FemABX peptidyl transferases are involved in non-ribosomal pentaglycine interpeptide bridge biosynthesis. Here, we characterized the phenotype of a Staphylococcus carnosus femB deletion mutant, which was affected in growth and showed pleiotropic effects such as enhanced methicillin sensitivity, lysostaphin resistance, cell clustering, and decreased peptidoglycan cross-linking. However, comparative secretome analysis revealed a most striking difference in the massive secretion or release of proteins into the culture supernatant in the femB mutant than the wild type. The secreted proteins can be categorized into typical cytosolic proteins and various murein hydrolases. As the transcription of the murein hydrolase genes was up-regulated in the mutant, they most likely represent an adaption response to the life threatening mutation. Even though the transcription of the cytosolic protein genes was unaltered, their high abundance in the supernatant of the mutant is most likely due to membrane leakage triggered by the weakened murein sacculus and enhanced autolysins.

  11. Faster-X adaptive protein evolution in house mice.

    PubMed

    Kousathanas, Athanasios; Halligan, Daniel L; Keightley, Peter D

    2014-04-01

    The causes of the large effect of the X chromosome in reproductive isolation and speciation have long been debated. The faster-X hypothesis predicts that X-linked loci are expected to have higher rates of adaptive evolution than autosomal loci if new beneficial mutations are on average recessive. Reproductive isolation should therefore evolve faster when contributing loci are located on the X chromosome. In this study, we have analyzed genome-wide nucleotide polymorphism data from the house mouse subspecies Mus musculus castaneus and nucleotide divergence from Mus famulus and Rattus norvegicus to compare rates of adaptive evolution for autosomal and X-linked protein-coding genes. We found significantly faster adaptive evolution for X-linked loci, particularly for genes with expression in male-specific tissues, but autosomal and X-linked genes with expression in female-specific tissues evolve at similar rates. We also estimated rates of adaptive evolution for genes expressed during spermatogenesis and found that X-linked genes that escape meiotic sex chromosome inactivation (MSCI) show rapid adaptive evolution. Our results suggest that faster-X adaptive evolution is either due to net recessivity of new advantageous mutations or due to a special gene content of the X chromosome, which regulates male function and spermatogenesis. We discuss how our results help to explain the large effect of the X chromosome in speciation.

  12. Incorporating adaptive responses into future projections of coral bleaching.

    PubMed

    Logan, Cheryl A; Dunne, John P; Eakin, C Mark; Donner, Simon D

    2014-01-01

    Climate warming threatens to increase mass coral bleaching events, and several studies have projected the demise of tropical coral reefs this century. However, recent evidence indicates corals may be able to respond to thermal stress though adaptive processes (e.g., genetic adaptation, acclimatization, and symbiont shuffling). How these mechanisms might influence warming-induced bleaching remains largely unknown. This study compared how different adaptive processes could affect coral bleaching projections. We used the latest bias-corrected global sea surface temperature (SST) output from the NOAA/GFDL Earth System Model 2 (ESM2M) for the preindustrial period through 2100 to project coral bleaching trajectories. Initial results showed that, in the absence of adaptive processes, application of a preindustrial climatology to the NOAA Coral Reef Watch bleaching prediction method overpredicts the present-day bleaching frequency. This suggests that corals may have already responded adaptively to some warming over the industrial period. We then modified the prediction method so that the bleaching threshold either permanently increased in response to thermal history (e.g., simulating directional genetic selection) or temporarily increased for 2-10 years in response to a bleaching event (e.g., simulating symbiont shuffling). A bleaching threshold that changes relative to the preceding 60 years of thermal history reduced the frequency of mass bleaching events by 20-80% compared with the 'no adaptive response' prediction model by 2100, depending on the emissions scenario. When both types of adaptive responses were applied, up to 14% more reef cells avoided high-frequency bleaching by 2100. However, temporary increases in bleaching thresholds alone only delayed the occurrence of high-frequency bleaching by ca. 10 years in all but the lowest emissions scenario. Future research should test the rate and limit of different adaptive responses for coral species across latitudes and

  13. Exposure to Stressful Environments: Strategy of Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Farhi, Leon E.

    1991-01-01

    Any new natural environment may generate a number of stresses (such as hypoxia, water lack, and heat exposure), each of which can produce strains in more than a single organ system. Every strain may in turn stimulate the body to adapt in multiple ways. Nevertheless, a general strategy of the various adaptive responses emerges when the challenges are divided into three groups. The first category includes conditions that affect the supply of essential molecules, while the second is made up by those stresses that prevent the body from regulating properly the output of waste products, such as CO2 and heat. In both classes, there is a small number of responses, similar in principle, regardless of the specific situation. The third unit is created by environments that disrupt body transport systems. Problems may arise when there is a conflict between two stresses requiring conflicting adaptive changes. An alternative to adaptation, creation of micro-environment, is often favored by the animal.

  14. Nucleocytoplasmic shuttling of the adapter protein SH2B1beta (SH2-Bbeta) is required for nerve growth factor (NGF)-dependent neurite outgrowth and enhancement of expression of a subset of NGF-responsive genes.

    PubMed

    Maures, Travis J; Chen, Linyi; Carter-Su, Christin

    2009-07-01

    The adapter protein SH2B1 (SH2-B, PSM) is recruited to multiple ligand-activated receptor tyrosine kinases, including the receptors for nerve growth factor (NGF), insulin, and IGF-I as well as the cytokine receptor-associated Janus kinase family kinases. In this study, we examine SH2B1's function in NGF signaling. We show that depleting endogenous SH2B1 using short hairpin RNA against SH2B1 inhibits NGF-dependent neurite outgrowth, but not NGF-mediated phosphorylation of Akt or ERKs 1/2. SH2B1 has been hypothesized to localize and function at the plasma membrane. We identify a nuclear localization signal within SH2B1 and show that it is required for nuclear translocation of SH2B1beta. Mutation of the nuclear localization signal has no effect on NGF-induced activation of TrkA and ERKs 1/2 but prevents SH2B1beta from enhancing NGF-induced neurite outgrowth. Disruption of SH2B1beta nuclear import also prevents SH2B1beta from enhancing NGF-induced transcription of genes important for neuronal differentiation, including those encoding urokinase plasminogen activator receptor, and matrix metalloproteinases 3 and 10. Disruption of SH2B1beta nuclear export by mutation of its nuclear export sequence similarly prevents SH2B1beta enhancement of NGF-induced transcription of those genes. Nuclear translocation of the highly homologous family member SH2B2(APS) was not observed. Together, these data suggest that rather than simply acting as an adapter protein linking signaling proteins to the activated TrkA receptor at the plasma membrane, SH2B1beta must shuttle between the plasma membrane and nucleus to function as a critical component of NGF-induced gene expression and neuronal differentiation.

  15. Mitochondrial role in adaptive response to stress conditions in preeclampsia

    PubMed Central

    Vishnyakova, Polina A.; Volodina, Maria A.; Tarasova, Nadezhda V.; Marey, Maria V.; Tsvirkun, Daria V.; Vavina, Olga V.; Khodzhaeva, Zulfiya S.; Kan, Natalya E.; Menon, Ramkumar; Vysokikh, Mikhail Yu.; Sukhikh, Gennady T.

    2016-01-01

    Preeclampsia (PE) is a pregnancy-specific syndrome, characterized in general by hypertension with proteinuria or other systemic disturbances. PE is the major cause of maternal and fetal morbidity and mortality worldwide. However, the etiology of PE still remains unclear. Our study involved 38 patients: 14 with uncomplicated pregnancy; 13 with early-onset PE (eoPE); and 11 with late-onset PE (loPE). We characterized the immunophenotype of cells isolated from the placenta and all biopsy samples were stained positive for Cytokeratin 7, SOX2, Nestin, Vimentin, and CD44. We obtained a significant increase in OPA1 mRNA and protein expression in the eoPE placentas. Moreover, TFAM expression was down-regulated in comparison to the control (p < 0.01). Mitochondrial DNA copy number in eoPE placentas was significantly higher than in samples from normal pregnancies. We observed an increase of maximum coupled state 3 respiration rate in mitochondria isolated from the placenta in the presence of complex I substrates in the eoPE group and an increase of P/O ratio, citrate synthase activity and decrease of Ca2+-induced depolarization rate in both PE groups. Our results suggest an essential role of mitochondrial activity changes in an adaptive response to the development of PE. PMID:27573305

  16. Mast cells in allergy: innate instructors of adaptive responses.

    PubMed

    Stelekati, Erietta; Orinska, Zane; Bulfone-Paus, Silvia

    2007-01-01

    The function of mast cells as effector cells in allergy has been extensively studied. However, increasing insight into mast cell physiology has revealed new mast cell functions and has introduced mast cells as key players in the regulation of innate as well as adaptive immunity. For example, mast cells have recently been found to express Toll-like receptors (TLRs), which enable them to participate in the innate immune response against pathogens. Furthermore, mast cells have been reported to interact with B cells, dendritic cells and T cells and thereby modulate the direction of an adaptive immune response. Finally, recent documentation that mast cells express functional MHC class II and costimulatory molecules and release immunologically active exosomes, has raised the possibility that mast cells also engage in (as yet) poorly understood antigen presentation functions. In this review, we explore the hypothesis that mast cells serve as central mediators between innate and adaptive immunity, rather as pure effector cells, during allergic innate responses.

  17. Adaptive resolution simulation of an atomistic protein in MARTINI water

    NASA Astrophysics Data System (ADS)

    Zavadlav, Julija; Melo, Manuel Nuno; Marrink, Siewert J.; Praprotnik, Matej

    2014-02-01

    We present an adaptive resolution simulation of protein G in multiscale water. We couple atomistic water around the protein with mesoscopic water, where four water molecules are represented with one coarse-grained bead, farther away. We circumvent the difficulties that arise from coupling to the coarse-grained model via a 4-to-1 molecule coarse-grain mapping by using bundled water models, i.e., we restrict the relative movement of water molecules that are mapped to the same coarse-grained bead employing harmonic springs. The water molecules change their resolution from four molecules to one coarse-grained particle and vice versa adaptively on-the-fly. Having performed 15 ns long molecular dynamics simulations, we observe within our error bars no differences between structural (e.g., root-mean-squared deviation and fluctuations of backbone atoms, radius of gyration, the stability of native contacts and secondary structure, and the solvent accessible surface area) and dynamical properties of the protein in the adaptive resolution approach compared to the fully atomistically solvated model. Our multiscale model is compatible with the widely used MARTINI force field and will therefore significantly enhance the scope of biomolecular simulations.

  18. Readapting the adaptive immune response - therapeutic strategies for atherosclerosis.

    PubMed

    Sage, Andrew P; Mallat, Ziad

    2017-01-04

    Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis as a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past three decades, but much remains to be done reduce disease burden. Current priorities include reducing atherosclerosis advancement to clinically significant stages and preventing plaque rupture or erosion. Inflammation and involvement of the adaptive immune system influences all these aspects and therefore is one focus for future therapeutic development. The atherosclerotic vascular wall is now recognized to be invaded from both sides (arterial lumen and adventitia), for better or worse, by the adaptive immune system. Atherosclerosis is also affected at several stages by adaptive immune responses, overall providing many opportunities to target these responses and to reduce disease progression. Protective influences that may be defective in diseased individuals include humoral responses to modified LDL and regulatory T cell responses. There are many strategies in development to boost these pathways in humans, including vaccine-based therapies. The effects of various existing adaptive immune targeting therapies, such as blocking critical co-stimulatory pathways or B cell depletion, on cardiovascular disease are beginning to emerge with important consequences for both autoimmune disease patients and the potential for wider use of such therapies. Entering the translation phase for adaptive immune targeting therapies is an exciting and promising prospect.

  19. Adaptive shaping of cortical response selectivity in the vibrissa pathway

    PubMed Central

    Zheng, He J. V.; Wang, Qi

    2015-01-01

    One embodiment of context-dependent sensory processing is bottom-up adaptation, where persistent stimuli decrease neuronal firing rate over hundreds of milliseconds. Adaptation is not, however, simply the fatigue of the sensory pathway, but shapes the information flow and selectivity to stimulus features. Adaptation enhances spatial discriminability (distinguishing stimulus location) while degrading detectability (reporting presence of the stimulus), for both the ideal observer of the cortex and awake, behaving animals. However, how the dynamics of the adaptation shape the cortical response and this detection and discrimination tradeoff is unknown, as is to what degree this phenomenon occurs on a continuum as opposed to a switching of processing modes. Using voltage-sensitive dye imaging in anesthetized rats to capture the temporal and spatial characteristics of the cortical response to tactile inputs, we showed that the suppression of the cortical response, in both magnitude and spatial spread, is continuously modulated by the increasing amount of energy in the adapting stimulus, which is nonuniquely determined by its frequency and velocity. Single-trial ideal observer analysis demonstrated a tradeoff between detectability and spatial discriminability up to a moderate amount of adaptation, which corresponds to the frequency range in natural whisking. This was accompanied by a decrease in both detectability and discriminability with high-energy adaptation, which indicates a more complex coupling between detection and discrimination than a simple switching of modes. Taken together, the results suggest that adaptation operates on a continuum and modulates the tradeoff between detectability and discriminability that has implications for information processing in ethological contexts. PMID:25787959

  20. Dietary protein for athletes: from requirements to optimum adaptation.

    PubMed

    Phillips, Stuart M; Van Loon, Luc J C

    2011-01-01

    Opinion on the role of protein in promoting athletic performance is divided along the lines of how much aerobic-based versus resistance-based activity the athlete undertakes. Athletes seeking to gain muscle mass and strength are likely to consume higher amounts of dietary protein than their endurance-trained counterparts. The main belief behind the large quantities of dietary protein consumption in resistance-trained athletes is that it is needed to generate more muscle protein. Athletes may require protein for more than just alleviation of the risk for deficiency, inherent in the dietary guidelines, but also to aid in an elevated level of functioning and possibly adaptation to the exercise stimulus. It does appear, however, that there is a good rationale for recommending to athletes protein intakes that are higher than the RDA. Our consensus opinion is that leucine, and possibly the other branched-chain amino acids, occupy a position of prominence in stimulating muscle protein synthesis; that protein intakes in the range of 1.3-1.8 g · kg(-1) · day(-1) consumed as 3-4 isonitrogenous meals will maximize muscle protein synthesis. These recommendations may also be dependent on training status: experienced athletes would require less, while more protein should be consumed during periods of high frequency/intensity training. Elevated protein consumption, as high as 1.8-2.0 g · kg(-1) · day(-1) depending on the caloric deficit, may be advantageous in preventing lean mass losses during periods of energy restriction to promote fat loss.

  1. Adaptation responses of crops to climate change

    SciTech Connect

    Seino, Hiroshi

    1993-12-31

    Appreciable global climatic responses to increasing levels of atmospheric CO{sub 2} and other trace gases are expected to take place over the next 50 to 80 years. Increasing atmospheric concentrations of carbon dioxide and other greenhouse gases are producing or will produce changes in the climate of the Earth. In particular, numerous efforts of climate modeling project very substantial increase of surface air temperature. In addition to a general warming of the atmosphere, the possibility of increased summer dryness in the continental mid-latitudes has been suggested on the basis of both historical analogues and some General Circulation Model (GCM) studies. There are three types of effect of climatic change on agriculture: (1) the physiological (direct) effect of elevated levels of atmospheric CO{sub 2} on crop plants and weeds, (2) the effect of changes in parameters of climate (e.g., temperature, precipitation, and solar radiation) on plants and animals, and (3) the effects of climate-related rises in sea-level on land use. The direct effects of elevated CO{sub 2} are on photosynthesis and respiration and thereby on growth, and there are additional effects of increased CO{sub 2} on development, yield quality and stomatal aperture and water use. A doubling of CO{sub 2} increases the instantaneous photosynthetic rate by 30% to 100%, depending on the other environmental conditions, and reduce water requirements of plants by reducing transpiration (per unit leaf area) through reductions in stomatal aperture. A doubling of CO{sub 2} causes partial stomatal closure on both C{sub 3} and C{sub 4} plants (approximately a 40% decrease in aperture). In many experiments this results in reductions of transpiration of about 23% to 46%. However. there is considerable uncertainty over the magnitude of this in natural conditions.

  2. Stimuli-Responsive Mechanically Adaptive Polymer Nanocomposites

    PubMed Central

    Shanmuganathan, Kadhiravan; Capadona, Jeffrey R.; Rowan, Stuart J.; Weder, Christoph

    2010-01-01

    A new series of biomimetic stimuli-responsive nanocomposites, which change their mechanical properties upon exposure to physiological conditions, was prepared and investigated. The materials were produced by introducing percolating networks of cellulose nanofibers or “whiskers” derived from tunicates into poly(vinyl acetate) (PVAc), poly(butyl methacrylate) (PBMA), and blends of these polymers, with the objective of determining how the hydrophobicity and glass-transition temperature (Tg) of the polymer matrix affect the water-induced mechanically dynamic behavior. Below the Tg (~60–70 °C), the incorporation of whiskers (15.1 – 16.5% v/v) modestly increased the tensile storage moduli (E′) of the neat polymers from 0.6 to 3.8 GPa (PBMA) and from 2 to 5.2 GPa (PVAc). The reinforcement was much more dramatic above Tg, where E′ increased from 1.2 to 690 MPa (PVAc) and ~1 to 1.1 GPa (PBMA). Upon exposure to physiological conditions (immersion in artificial cerebrospinal fluid, ACSF, at 37 °C) all materials displayed a decrease of E′. The most significant contrast was seen in PVAc; for example the E′ of a 16.5% v/v PVAc/whisker nanocomposite decreased from 5.2 GPa to 12.7 MPa. Only a modest modulus decrease was measured for PBMA/whisker nanocomposite; here the E′ of a 15.1% v/v PBMA/whisker nanocomposite decreased from 3.8 to 1.2 GPa. A systematic investigation revealed that the magnitude of the mechanical contrast was related to the degree of swelling with ACSF, which was shown to increase with whisker content, temperature, and polarity of the matrix (PVAc > PBMA). The mechanical morphing of the new materials can be described in the framework of both the percolation and Halpin-Kardos models for nanocomposite reinforcement, and is the result of changing interactions among the nanoparticles and plasticization of the matrix upon swelling. PMID:20305827

  3. Genetic erosion impedes adaptive responses to stressful environments

    PubMed Central

    Bijlsma, R; Loeschcke, Volker

    2012-01-01

    Biodiversity is increasingly subjected to human-induced changes of the environment. To persist, populations continually have to adapt to these often stressful changes including pollution and climate change. Genetic erosion in small populations, owing to fragmentation of natural habitats, is expected to obstruct such adaptive responses: (i) genetic drift will cause a decrease in the level of adaptive genetic variation, thereby limiting evolutionary responses; (ii) inbreeding and the concomitant inbreeding depression will reduce individual fitness and, consequently, the tolerance of populations to environmental stress. Importantly, inbreeding generally increases the sensitivity of a population to stress, thereby increasing the amount of inbreeding depression. As adaptation to stress is most often accompanied by increased mortality (cost of selection), the increase in the ‘cost of inbreeding’ under stress is expected to severely hamper evolutionary adaptive processes. Inbreeding thus plays a pivotal role in this process and is expected to limit the probability of genetically eroded populations to successfully adapt to stressful environmental conditions. Consequently, the dynamics of small fragmented populations may differ considerably from large nonfragmented populations. The resilience of fragmented populations to changing and deteriorating environments is expected to be greatly decreased. Alleviating inbreeding depression, therefore, is crucial to ensure population persistence. PMID:25568035

  4. Functional constraints on adaptive evolution of protein ubiquitination sites

    PubMed Central

    Lu, Liang; Li, Yang; Liu, Zhongyang; Liang, Fengji; Guo, Feifei; Yang, Shuai; Wang, Dan; He, Yangzhige; Xiong, Jianghui; Li, Dong; He, Fuchu

    2017-01-01

    It is still unclear whether there exist functional constraints on the evolution of protein ubiquitination sites, because most previous studies regarded all protein ubiquitination sites as a whole or only focused on limited structural properties. We tried to clarify the relation between functional constraints and ubiquitination sites evolution. We investigated the evolutionary conservation of human ubiquitination sites in a broad evolutionary scale from G. gorilla to S. pombe, and we found that in organisms originated after the divergence of vertebrate, ubiquitination sites are more conserved than their flanking regions, while the opposite tendency is observed before this divergence time. By grouping the ubiquitination proteins into different functional categories, we confirm that many functional constraints like certain molecular functions, protein tissue expression specificity and protein connectivity in protein-protein interaction network enhance the evolutionary conservation of ubiquitination sites. Furthermore, by analyzing the gains of ubiquitination sites at different divergence time and their functional characters, we validate that the emergences of ubiquitination sites at different evolutionary time were also affected by the uncovered functional constraints. The above results suggest that functional constraints on the adaptive evolution of ubiquitination sites increase the opportunity for ubiquitination to synthetically regulate various cellular and developmental processes during evolution. PMID:28054638

  5. Adaptation responses to climate change differ between global megacities

    NASA Astrophysics Data System (ADS)

    Georgeson, Lucien; Maslin, Mark; Poessinouw, Martyn; Howard, Steve

    2016-06-01

    Urban areas are increasingly at risk from climate change, with negative impacts predicted for human health, the economy and ecosystems. These risks require responses from cities to improve their resilience. Policymakers need to understand current adaptation spend to plan comprehensively and effectively. Through the measurement of spend in the newly defined `adaptation economy', we analyse current climate change adaptation efforts in ten megacities. In all cases, the adaptation economy remains a small part of the overall economy, representing a maximum of 0.33% of a city's gross domestic product (here referred to as GDPc). Differences in total spend are significant between cities in developed, emerging and developing countries, ranging from #15 million to #1,600 million. Comparing key subsectors, we demonstrate the differences in adaptation profiles. Developing cities have higher proportional spend on health and agriculture, whereas developed cities have higher spend on energy and water. Spend per capita and percentage of GDPc comparisons more clearly show disparities between cities. Developing country cities spend half the proportion of GDPc and significantly less per capita, suggesting that adaptation spend is driven by wealth rather than the number of vulnerable people. This indicates that current adaptation activities are insufficient in major population centres in developing and emerging economies.

  6. Replicated evolution of integrated plastic responses during early adaptive divergence.

    PubMed

    Parsons, Kevin J; Robinson, Beren W

    2006-04-01

    Colonization of a novel environment is expected to result in adaptive divergence from the ancestral population when selection favors a new phenotypic optimum. Local adaptation in the new environment occurs through the accumulation and integration of character states that positively affect fitness. The role played by plastic traits in adaptation to a novel environment has generally been ignored, except for variable environments. We propose that if conditions in a relatively stable but novel environment induce phenotypically plastic responses in many traits, and if genetic variation exists in the form of those responses, then selection may initially favor the accumulation and integration of functionally useful plastic responses. Early divergence between ancestral and colonist forms will then occur with respect to their plastic responses across the gradient bounded by ancestral and novel environmental conditions. To test this, we compared the magnitude, integration, and pattern of plastic character responses in external body form induced by shallow versus open water conditions between two sunfish ecomorphs that coexist in four postglacial lakes. The novel sunfish ecomorph is present in the deeper open water habitat, whereas the ancestral ecomorph inhabits the shallow waters along the lake margin. Plastic responses by open water ecomorphs were more correlated than those of their local shallow water ecomorph in two of the populations, whereas equal levels of correlated plastic character responses occurred between ecomorphs in the other two populations. Small but persistent differences occurred between ecomorph pairs in the pattern of their character responses, suggesting a recent divergence. Open water ecomorphs shared some similarities in the covariance among plastic responses to rearing environment. Replication in the form of correlated plastic responses among populations of open water ecomorphs suggests that plastic character states may evolve under selection

  7. Beyond Adapting to Climate Change: Embedding Adaptation in Responses to Multiple Threats and Stresses

    SciTech Connect

    Wilbanks, Thomas J; Kates, Dr. Robert W.

    2010-01-01

    Climate change impacts are already being experienced in every region of the United States and every part of the world most severely in Arctic regions and adaptation is needed now. Although climate change adaptation research is still in its infancy, significant adaptation planning in the United States has already begun in a number of localities. This article seeks to broaden the adaptation effort by integrating it with broader frameworks of hazards research, sustainability science, and community and regional resilience. To extend the range of experience, we draw from ongoing case studies in the Southeastern United States and the environmental history of New Orleans to consider the multiple threats and stresses that all communities and regions experience. Embedding climate adaptation in responses to multiple threats and stresses helps us to understand climate change impacts, themselves often products of multiple stresses, to achieve community acceptance of needed adaptations as co-benefits of addressing multiple threats, and to mainstream the process of climate adaptation through the larger envelope of social relationships, communication channels, and broad-based awareness of needs for risk management that accompany community resilience.

  8. Neural Basis of Adaptive Response Time Adjustment during Saccade Countermanding

    PubMed Central

    Pouget, Pierre; Logan, Gordon D.; Palmeri, Thomas J.; Boucher, Leanne; Paré, Martin; Schall, Jeffrey D.

    2011-01-01

    Humans and macaque monkeys adjust their response time adaptively in stop signal (countermanding) tasks, responding slower after stop-signal trials than after control trials with no stop signal. We investigated the neural mechanism underlying this adaptive response time adjustment in macaque monkeys performing a saccade countermanding task. Earlier research showed that movements are initiated when the random accumulation of presaccadic movement-related activity reaches a fixed threshold. We found that a systematic delay in response time after stop signal trials was accomplished not through a change of threshold, baseline, or accumulation rate, but instead through a change in the time when activity first began to accumulate. The neurons underlying movement initiation have been identified with mathematical accumulator models of response time performance. Therefore, this new result provides surprising new insights into the neural instantiation of stochastic accumulator models and the mechanisms through which executive control can be exerted. PMID:21880921

  9. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Del Giudice, Marco; Hinnant, J. Benjamin; Ellis, Bruce J.; El-Sheikh, Mona

    2012-01-01

    The adaptive calibration model (ACM) is an evolutionary-developmental theory of individual differences in stress responsivity. In this article, we tested some key predictions of the ACM in a middle childhood sample (N = 256). Measures of autonomic nervous system activity across the sympathetic and parasympathetic branches validated the 4-pattern…

  10. Dynamics and Adaptive Benefits of Protein Domain Emergence and Arrangements during Plant Genome Evolution

    PubMed Central

    Kersting, Anna R.; Bornberg-Bauer, Erich; Moore, Andrew D.; Grath, Sonja

    2012-01-01

    Plant genomes are generally very large, mostly paleopolyploid, and have numerous gene duplicates and complex genomic features such as repeats and transposable elements. Many of these features have been hypothesized to enable plants, which cannot easily escape environmental challenges, to rapidly adapt. Another mechanism, which has recently been well described as a major facilitator of rapid adaptation in bacteria, animals, and fungi but not yet for plants, is modular rearrangement of protein-coding genes. Due to the high precision of profile-based methods, rearrangements can be well captured at the protein level by characterizing the emergence, loss, and rearrangements of protein domains, their structural, functional, and evolutionary building blocks. Here, we study the dynamics of domain rearrangements and explore their adaptive benefit in 27 plant and 3 algal genomes. We use a phylogenomic approach by which we can explain the formation of 88% of all arrangements by single-step events, such as fusion, fission, and terminal loss of domains. We find many domains are lost along every lineage, but at least 500 domains are novel, that is, they are unique to green plants and emerged more or less recently. These novel domains duplicate and rearrange more readily within their genomes than ancient domains and are overproportionally involved in stress response and developmental innovations. Novel domains more often affect regulatory proteins and show a higher degree of structural disorder than ancient domains. Whereas a relatively large and well-conserved core set of single-domain proteins exists, long multi-domain arrangements tend to be species-specific. We find that duplicated genes are more often involved in rearrangements. Although fission events typically impact metabolic proteins, fusion events often create new signaling proteins essential for environmental sensing. Taken together, the high volatility of single domains and complex arrangements in plant genomes

  11. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    PubMed

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  12. Bayesian optimal response-adaptive design for binary responses using stopping rule.

    PubMed

    Komaki, Fumiyasu; Biswas, Atanu

    2016-05-02

    Response-adaptive designs are used in phase III clinical trials to allocate a larger number of patients to the better treatment arm. Optimal designs are explored in the recent years in the context of response-adaptive designs, in the frequentist view point only. In the present paper, we propose some response-adaptive designs for two treatments based on Bayesian prediction for phase III clinical trials. Some properties are studied and numerically compared with some existing competitors. A real data set is used to illustrate the applicability of the proposed methodology where we redesign the experiment using parameters derived from the data set.

  13. Late embryogenesis abundant proteins: versatile players in the plant adaptation to water limiting environments.

    PubMed

    Olvera-Carrillo, Yadira; Luis Reyes, José; Covarrubias, Alejandra A

    2011-04-01

    Late Embryogenesis Abundant (LEA) proteins accumulate at the onset of seed desiccation and in response to water deficit in vegetative plant tissues. The typical LEA proteins are highly hydrophilic and intrinsically unstructured. They have been classified in different families; each one showing distinctive conserved motifs. In this manuscript we present and discuss some of the recent findings regarding their role in plant adaptation to water deficit, as well as those concerning to their possible function, and how it can be related to their intrinsic structural flexibility.

  14. The Dose Window for Radiation-Induced Protective Adaptive Responses

    PubMed Central

    Mitchel, Ronald E. J.

    2009-01-01

    Adaptive responses to low doses of low LET radiation occur in all organisms thus far examined, from single cell lower eukaryotes to mammals. These responses reduce the deleterious consequences of DNA damaging events, including radiation-induced or spontaneous cancer and non-cancer diseases in mice. The adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGy for a single low dose rate exposure. However, these thresholds for protection are not a fixed function of total dose, but also vary with dose rate, additional radiation or non-radiation stressors, tissue type and p53 functional status. Exposures above the upper threshold are generally detrimental, while exposures below the lower threshold may or may not increase either cancer or non-cancer disease risk. PMID:20585438

  15. A Comparison of Rosetta Stones in Adapter Protein Families

    PubMed Central

    Kumar, Hulikal Shivashankara Santosh; Kumar, Vadlapudi

    2016-01-01

    The inventory of proteins used in different kingdoms appears surprisingly similar in all sequenced eukaryotic genome. Protein domains represent the basic evolutionary units that form proteins. Domain duplication and shuffling by recombination are probably the most important forces driving protein evolution and hence the complexity of the proteome. While the duplication of whole genes as well as domain encoding exons increases the abundance of domains in the proteome, domain shuffling increases versatility, i.e. the number of distinct contexts in which a domain can occur. In this study we considered five important adapter domain families namely WD40, KELCH, Ankyrin, PDZ and Pleckstrin Homology (PH domain) family for the comparison of Domain versatility, Abundance and domain sharing between them. We used ecological statistics methods such as Jaccard’s Similarity Index (JSI), Detrended Correspondence Analysis, k-Means clustering for the domain distribution data. We found high propensity of domain sharing between PH and PDZ. We found higher abundance of only few selected domains in PH, PDZ, ANK and KELCH families. We also found WD40 family with high versatility and less redundant domain occurrence, with less domain sharing. Hence, the assignments of functions to more orphan WD40 proteins that will help in the identification of suitable drug targets. PMID:28246462

  16. The Influence of Innate and Adaptive Immune Responses on Atherosclerosis

    PubMed Central

    Witztum, Joseph L.; Lichtman, Andrew H.

    2014-01-01

    Both the chronic development of atherosclerotic lesions and the acute changes in lesion phenotype that lead to clinical cardiovascular events are significantly influenced by the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall. The rapid pace of discovery of mechanisms of immunologic recognition, effector functions, and regulation has significantly influenced the study of atherosclerosis, and our new knowledge is beginning to affect how we treat this ubiquitous disease. In this review, we discuss recent advances in our understanding of how innate and adaptive immunity contribute to atherosclerosis, as well as therapeutic opportunities that arise from this knowledge. PMID:23937439

  17. Bioenergetic adaptation in response to autophagy regulators during rotenone exposure

    PubMed Central

    Giordano, Samantha; Dodson, Matthew; Ravi, Saranya; Redmann, Matthew; Ouyang, Xiaosen; Usmar, Victor M Darley; Zhang, Jianhua

    2015-01-01

    Parkinson’s disease (PD) is the second most common neurodegenerative disorder with both mitochondrial dysfunction and insufficient autophagy playing a key role in its pathogenesis. Among the risk factors, exposure to the environmental neurotoxin rotenone increases the probability of developing PD. We previously reported that in differentiated SH-SY5Y cells, rotenone-induced cell death is directly related to inhibition of mitochondrial function. How rotenone at nM concentrations inhibits mitochondrial function, and whether it can engage the autophagy pathway necessary to remove damaged proteins and organelles, is unknown. We tested the hypothesis that autophagy plays a protective role against rotenone toxicity in primary neurons. We found that rotenone (10–100 nM) immediately inhibited cellular bioenergetics. Concentrations that decreased mitochondrial function at 2 hr, caused cell death at 24 hr with an LD50 of 10 nM. Overall autophagic flux was decreased by 10 nM rotenone at both 2 and 24 hr, but surprisingly mitophagy, or autophagy of the mitochondria, was increased at 24 hr, suggesting that a mitochondrial-specific lysosomal degradation pathway may be activated. Upregulation of autophagy by rapamycin protected against cell death while inhibition of autophagy by 3-methyladenine (3-MA) exacerbated cell death. Interestingly, while 3-MA exacerbated the rotenone-dependent effects on bioenergetics, rapamycin did not prevent rotenone-induced mitochondrial dysfunction, but caused reprogramming of mitochondrial substrate usage associated with both complex I and complex II activities. Taken together, these data demonstrate that autophagy can play a protective role in primary neuron survival in response to rotenone; moreover, surviving neurons exhibit bioenergetic adaptations to this metabolic stressor. PMID:25081478

  18. Immune and stress responses in oysters with insights on adaptation.

    PubMed

    Guo, Ximing; He, Yan; Zhang, Linlin; Lelong, Christophe; Jouaux, Aude

    2015-09-01

    Oysters are representative bivalve molluscs that are widely distributed in world oceans. As successful colonizers of estuaries and intertidal zones, oysters are remarkably resilient against harsh environmental conditions including wide fluctuations in temperature and salinity as well as prolonged air exposure. Oysters have no adaptive immunity but can thrive in microbe-rich estuaries as filter-feeders. These unique adaptations make oysters interesting models to study the evolution of host-defense systems. Recent advances in genomic studies including sequencing of the oyster genome have provided insights into oyster's immune and stress responses underlying their amazing resilience. Studies show that the oyster genomes are highly polymorphic and complex, which may be key to their resilience. The oyster genome has a large gene repertoire that is enriched for immune and stress response genes. Thousands of genes are involved in oyster's immune and stress responses, through complex interactions, with many gene families expanded showing high sequence, structural and functional diversity. The high diversity of immune receptors and effectors may provide oysters with enhanced specificity in immune recognition and response to cope with diverse pathogens in the absence of adaptive immunity. Some members of expanded immune gene families have diverged to function at different temperatures and salinities or assumed new roles in abiotic stress response. Most canonical innate immunity pathways are conserved in oysters and supported by a large number of diverse and often novel genes. The great diversity in immune and stress response genes exhibited by expanded gene families as well as high sequence and structural polymorphisms may be central to oyster's adaptation to highly stressful and widely changing environments.

  19. Interferon regulatory factor 3 in adaptive immune responses.

    PubMed

    Ysebrant de Lendonck, Laure; Martinet, Valerie; Goriely, Stanislas

    2014-10-01

    Interferon regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Indeed, activation of this transcription factor triggers the expression of type I interferons and downstream interferon-stimulated genes in infected cells. Recent evidences indicate that this pathway also modulates adaptive immune responses. This review focuses on the different mechanisms that are implicated in this process. We discuss the role of IRF3 within antigen-presenting cells and T lymphocytes in the polarization of the cellular immune response and its implication in the pathogenesis of immune disorders.

  20. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    EPA Science Inventory

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-Dose
    Cancer Responses
    .
    There has been a concerted effort in the field of radiation biology to better understand cellular
    responses that could have an impact on the estin1ation of cancer...

  1. Electrophoresis and spectrometric analyses of adaptation-related proteins in thermally stressed Chromobacterium violaceum.

    PubMed

    Cordeiro, I B; Castro, D P; Nogueira, P P O; Angelo, P C S; Nogueira, P A; Gonçalves, J F C; Pereira, A M R F; Garcia, J S; Souza, G H M F; Arruda, M A Z; Eberlin, M N; Astolfi-Filho, S; Andrade, E V; López-Lozano, J L

    2013-10-29

    Chromobacterium violaceum is a Gram-negative proteobacteria found in water and soil; it is widely distributed in tropical and subtropical regions, such as the Amazon rainforest. We examined protein expression changes that occur in C. violaceum at different growth temperatures using electrophoresis and mass spectrometry. The total number of spots detected was 1985; the number ranged from 99 to 380 in each assay. The proteins that were identified spectrometrically were categorized as chaperones, proteins expressed exclusively under heat stress, enzymes involved in the respiratory and fermentation cycles, ribosomal proteins, and proteins related to transport and secretion. Controlling inverted repeat of chaperone expression and inverted repeat DNA binding sequences, as well as regions recognized by sigma factor 32, elements involved in the genetic regulation of the bacterial stress response, were identified in the promoter regions of several of the genes coding proteins, involved in the C. violaceum stress response. We found that 30 °C is the optimal growth temperature for C. violaceum, whereas 25, 35, and 40 °C are stressful temperatures that trigger the expression of chaperones, superoxide dismutase, a probable small heat shock protein, a probable phasing, ferrichrome-iron receptor protein, elongation factor P, and an ornithine carbamoyltransferase catabolite. This information improves our comprehension of the mechanisms involved in stress adaptation by C. violaceum.

  2. Adaptive optics and phase diversity imaging for responsive space applications.

    SciTech Connect

    Smith, Mark William; Wick, David Victor

    2004-11-01

    The combination of phase diversity and adaptive optics offers great flexibility. Phase diverse images can be used to diagnose aberrations and then provide feedback control to the optics to correct the aberrations. Alternatively, phase diversity can be used to partially compensate for aberrations during post-detection image processing. The adaptive optic can produce simple defocus or more complex types of phase diversity. This report presents an analysis, based on numerical simulations, of the efficiency of different modes of phase diversity with respect to compensating for specific aberrations during post-processing. It also comments on the efficiency of post-processing versus direct aberration correction. The construction of a bench top optical system that uses a membrane mirror as an active optic is described. The results of characterization tests performed on the bench top optical system are presented. The work described in this report was conducted to explore the use of adaptive optics and phase diversity imaging for responsive space applications.

  3. The adaptive response of jaw muscles to varying functional demands.

    PubMed

    Grünheid, Thorsten; Langenbach, Geerling E J; Korfage, Joannes A M; Zentner, Andrej; van Eijden, Theo M G J

    2009-12-01

    Jaw muscles are versatile entities that are able to adapt their anatomical characteristics, such as size, cross-sectional area, and fibre properties, to altered functional demands. The dynamic nature of muscle fibres allows them to change their phenotype to optimize the required contractile function while minimizing energy use. Changes in these anatomical parameters are associated with changes in neuromuscular activity as the pattern of muscle activation by the central nervous system plays an important role in the modulation of muscle properties. This review summarizes the adaptive response of jaw muscles to various stimuli or perturbations in the orofacial system and addresses general changes in muscles as they adapt, specific adaptive changes in jaw muscles under various physiologic and pathologic conditions, and their adaptive response to non-surgical and surgical therapeutic interventions. Although the jaw muscles are used concertedly in the masticatory system, their adaptive changes are not always uniform and vary with the nature, intensity, and duration of the stimulus. In general, stretch, increases neuromuscular activity, and resistance training result in hypertrophy, elicits increases in mitochondrial content and cross-sectional area of the fibres, and may change the fibre-type composition of the muscle towards a larger percentage of slow-type fibres. In contrast, changes in the opposite direction occur when neuromuscular activity is reduced, the muscle is immobilized in a shortened position, or paralysed. The broad range of stimuli that affect the properties of jaw muscles might help explain the large variability in the anatomical and physiological characteristics found among individuals, muscles, and muscle portions.

  4. Seed Pubescence and Shape Modulate Adaptive Responses to Fire Cues.

    PubMed

    Gómez-González, Susana; Ojeda, Fernando; Torres-Morales, Patricio; Palma, Jazmín E

    2016-01-01

    Post-fire recruitment by seeds is regarded as an adaptive response in fire-prone ecosystems. Nevertheless, little is known about which heritable seed traits are functional to the main signals of fire (heat and smoke), thus having the potential to evolve. Here, we explored whether three seed traits (pubescence, dormancy and shape) and fire regime modulate seed response to fire cues(heat and smoke). As a model study system, we used Helenium aromaticum (Asteraceae), a native annual forb from the Chilean matorral, where fires are anthropogenic. We related seed trait values with fitness responses (germination and survival) after exposure to heat-shock and smoke experimental treatments on seeds from 10 H. aromaticum wild populations. We performed a phenotypic selection experiment to examine the relationship of seed traits with post-treatment fitness within a population (adaptive hypothesis). We then explored whether fire frequency in natural habitats was associated with trait expression across populations, and with germination and survival responses to experimental fire-cues. We found that populations subjected to higher fire frequency had, in average, more rounded and pubescent seeds than populations from rarely burned areas. Populations with more rounded and pubescent seeds were more resistant to 80°C heat-shock and smoke treatments.There was correlated selection on seed traits: pubescent-rounded or glabrouscent-elongated seeds had the highest probability of germinating after heat-shock treatments. Seed pubescence and shape in H. aromaticum are heritable traits that modulate adaptive responses to fire. Our results provide new insights into the process of plant adaptation to fire and highlight the relevance of human-made fires as a strong evolutionary agent in the Anthropocene.

  5. Adaptive thermoregulation in endotherms may alter responses to climate change.

    PubMed

    Boyles, Justin G; Seebacher, Frank; Smit, Ben; McKechnie, Andrew E

    2011-11-01

    Climate change is one of the major issues facing natural populations and thus a focus of recent research has been to predict the responses of organisms to these changes. Models are becoming more complex and now commonly include physiological traits of the organisms of interest. However, endothermic species have received less attention than have ectotherms in these mechanistic models. Further, it is not clear whether responses of endotherms to climate change are modified by variation in thermoregulatory characteristics associated with phenotypic plasticity and/or adaptation to past selective pressures. Here, we review the empirical data on thermal adaptation and acclimatization in endotherms and discuss how those factors may be important in models of responses to climate change. We begin with a discussion of why thermoregulation and thermal sensitivity at high body temperatures should be co-adapted. Importantly, we show that there is, in fact, considerable variation in the ability of endotherms to tolerate high body temperatures and/or high environmental temperatures, but a better understanding of this variation will likely be critical for predicting responses to future climatic scenarios. Next, we discuss why variation in thermoregulatory characteristics should be considered when modeling the effects of climate change on heterothermic endotherms. Finally, we review some biophysical and biochemical factors that will limit adaptation and acclimation in endotherms. We consider both long-term, directional climate change and short-term (but increasingly common) anomalies in climate such as extreme heat waves and we suggest areas of important future research relating to both our basic understanding of endothermic thermoregulation and the responses of endotherms to climate change.

  6. Seed Pubescence and Shape Modulate Adaptive Responses to Fire Cues

    PubMed Central

    Gómez-González, Susana; Ojeda, Fernando; Torres-Morales, Patricio; Palma, Jazmín E.

    2016-01-01

    Post-fire recruitment by seeds is regarded as an adaptive response in fire-prone ecosystems. Nevertheless, little is known about which heritable seed traits are functional to the main signals of fire (heat and smoke), thus having the potential to evolve. Here, we explored whether three seed traits (pubescence, dormancy and shape) and fire regime modulate seed response to fire cues(heat and smoke). As a model study system, we used Helenium aromaticum (Asteraceae), a native annual forb from the Chilean matorral, where fires are anthropogenic. We related seed trait values with fitness responses (germination and survival) after exposure to heat-shock and smoke experimental treatments on seeds from 10 H. aromaticum wild populations. We performed a phenotypic selection experiment to examine the relationship of seed traits with post-treatment fitness within a population (adaptive hypothesis). We then explored whether fire frequency in natural habitats was associated with trait expression across populations, and with germination and survival responses to experimental fire-cues. We found that populations subjected to higher fire frequency had, in average, more rounded and pubescent seeds than populations from rarely burned areas. Populations with more rounded and pubescent seeds were more resistant to 80°C heat-shock and smoke treatments.There was correlated selection on seed traits: pubescent-rounded or glabrouscent-elongated seeds had the highest probability of germinating after heat-shock treatments. Seed pubescence and shape in H. aromaticum are heritable traits that modulate adaptive responses to fire. Our results provide new insights into the process of plant adaptation to fire and highlight the relevance of human-made fires as a strong evolutionary agent in the Anthropocene. PMID:27438267

  7. Adaptive response of single and binary Pseudomonas aeruginosa and Escherichia coli biofilms to benzalkonium chloride.

    PubMed

    Machado, Idalina; Lopes, Susana Patrícia; Sousa, Ana Margarida; Pereira, Maria Olívia

    2012-02-01

    The main goal of this work was to examine whether the continuous exposure of single and binary P. aeruginosa and E. coli biofilms to sub-lethal benzalkonium chloride (BC) doses can induce adaptive response of bacteria. Biofilms were formed during 24 h and then put continuously in contact with BC for more 5 days. The six-day-old adapted biofilms were then submitted to BC challenge, characterized and inspected by SEM. Both single and binary adapted biofilms have clearly more biomass, polysaccharides and proteins and less activity even though the number of cells was identical. After BC treatment, adapted biofilms maintained their mass and activity. SEM examination revealed that those adapted biofilms had a slimier and denser matrix that became thicker after BC treatment. Continuous exposure of bacteria to antimicrobials can lead to development of biofilms encompassing more virulent and tolerant bacteria. This adaptive resistance can be the result of a phenotypic adaptation, a genetic acquired resistance or both. Instead of eradicating biofilms and kill microorganisms, the use of a disinfectant can, favour biofilm formation and tolerance. This must be a genuine concern as it can happen in clinical environments, where the use of antimicrobials is unavoidable.

  8. Global relationships in fluctuation and response in adaptive evolution

    PubMed Central

    Furusawa, Chikara; Kaneko, Kunihiko

    2015-01-01

    Cells change their internal state to adapt to environmental changes, and evolve in response to the new conditions. The phenotype changes first via adaptation in response to environmental changes, and then through mutational changes in the genomic sequence, followed by selection in evolution. Here, we analysed simulated adaptive evolution using a simple cell model consisting of thousands of intracellular components, and found that the changes in their concentrations by adaptation are proportional to those by evolution across all the components, where the proportion coefficient between the two agreed well with the change in the growth rate of a cell. Furthermore, we demonstrate that the phenotypic variance in concentrations of cellular components due to (non-genetic) noise and to genomic alternations is proportional across all components. This implies that the specific phenotypes that are highly evolvable were already given by non-genetic fluctuations. These global relationships in cellular states were also supported by phenomenological theory based on steady reproduction and transcriptome analysis of laboratory evolution in Escherichia coli. These findings demonstrate that a possible evolutionary change in phenotypic state is highly restricted. Our results provide a basis for the development of a quantitative theory of plasticity and robustness in phenotypic evolution. PMID:26202686

  9. Membrane vesicle production by Chlamydia trachomatis as an adaptive response

    PubMed Central

    Frohlich, Kyla M.; Hua, Ziyu; Quayle, Alison J.; Wang, Jin; Lewis, Maria E.; Chou, Chau-wen; Luo, Miao; Buckner, Lyndsey R.; Shen, Li

    2014-01-01

    Bacteria have evolved specific adaptive responses to cope with changing environments. These adaptations include stress response phenotypes with dynamic modifications of the bacterial cell envelope and generation of membrane vesicles (MVs). The obligate intracellular bacterium, Chlamydia trachomatis, typically has a biphasic lifestyle, but can enter into an altered growth state typified by morphologically aberrant chlamydial forms, termed persistent growth forms, when induced by stress in vitro. How C. trachomatis can adapt to a persistent growth state in host epithelial cells in vivo is not well understood, but is an important question, since it extends the host-bacterial relationship in vitro and has thus been indicated as a survival mechanism in chronic chlamydial infections. Here, we review recent findings on the mechanistic aspects of bacterial adaptation to stress with a focus on how C. trachomatis remodels its envelope, produces MVs, and the potential important consequences of MV production with respect to host-pathogen interactions. Emerging data suggest that the generation of MVs may be an important mechanism for C. trachomatis intracellular survival of stress, and thus may aid in the establishment of a chronic infection in human genital epithelial cells. PMID:24959424

  10. Higher Plants in Space: Microgravity Perception, Response, and Adaptation

    NASA Astrophysics Data System (ADS)

    Zheng, Hui Qiong; Han, Fei; Le, Jie

    2015-11-01

    Microgravity is a major abiotic stress in space. Its effects on plants may depend on the duration of exposure. We focused on two different phases of microgravity responses in space. When higher plants are exposed to short-term (seconds to hours) microgravity, such as on board parabolic flights and sounding rockets, their cells usually exhibit abiotic stress responses. For example, Ca 2+-, lipid-, and pH-signaling are rapidly enhanced, then the production of reactive oxygen species and other radicals increase dramatically along with changes in metabolism and auxin signaling. Under long-term (days to months) microgravity exposure, plants acclimatize to the stress by changing their metabolism and oxidative response and by enhancing other tropic responses. We conclude by suggesting that a systematic analysis of regulatory networks at the molecular level of higher plants is needed to understand the molecular signals in the distinct phases of the microgravity response and adaptation.

  11. Adaptation.

    PubMed

    Broom, Donald M

    2006-01-01

    welfare can be very good when it is occurring. Other adaptation is difficult and may involve lower or higher level emergency physiological responses or abnormal behaviour, often with bad feelings such as pain or fear. In that case, welfare is poor or very poor even if complete adaptation eventually occurs and there is no long-term threat to the life of the individual. In some circumstances, adaptation may be unsuccessful, the individual is not able to cope, stress occurs and welfare is ultimately very poor.

  12. Landowner response to wildfire risk: Adaptation, mitigation or doing nothing.

    PubMed

    Gan, Jianbang; Jarrett, Adam; Johnson Gaither, Cassandra

    2015-08-15

    Wildfire has brought about ecological, economic, and social consequences that engender human responses in many parts of the world. How to respond to wildfire risk is a common challenge across the globe particularly in areas where lands are controlled by many small private owners because effective wildfire prevention and protection require coordinated efforts of neighboring stakeholders. We explore (i) wildfire response strategies adopted by family forestland owners in the southern United States, one of the most important and productive forest regions in the world, through a landowner survey; and (ii) linkages between the responses of these landowners and their characteristics via multinomial logistic regression. We find that landowners used diverse strategies to respond to wildfire risk, with the most popular responses being "doing nothing" and combined adaptation and mitigation, followed by adaptation or mitigation alone. Landowners who had lost properties to wildfire, lived on their forestlands, had a forest management plan, and were better educated were more likely to proactively respond to wildfire risk. Our results indicate the possibility to enhance the effectiveness of collective action of wildfire risk response by private forestland owners and to coordinate wildfire response with forest conservation and certification efforts. These findings shed new light on engaging private landowners in wildfire management in the study region and beyond.

  13. Biological Bases for Radiation Adaptive Responses in the Lung

    SciTech Connect

    Scott, Bobby R.; Lin, Yong; Wilder, Julie; Belinsky, Steven

    2015-03-01

    Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis which now is known to be unsupported by a large volume of data.

  14. Unfolded protein response in cancer: the Physician's perspective

    PubMed Central

    2011-01-01

    The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials. PMID:21345215

  15. Universal response-adaptation relation in bacterial chemotaxis.

    PubMed

    Krembel, Anna K; Neumann, Silke; Sourjik, Victor

    2015-01-01

    The bacterial strategy of chemotaxis relies on temporal comparisons of chemical concentrations, where the probability of maintaining the current direction of swimming is modulated by changes in stimulation experienced during the recent past. A short-term memory required for such comparisons is provided by the adaptation system, which operates through the activity-dependent methylation of chemotaxis receptors. Previous theoretical studies have suggested that efficient navigation in gradients requires a well-defined adaptation rate, because the memory time scale needs to match the duration of straight runs made by bacteria. Here we demonstrate that the chemotaxis pathway of Escherichia coli does indeed exhibit a universal relation between the response magnitude and adaptation time which does not depend on the type of chemical ligand. Our results suggest that this alignment of adaptation rates for different ligands is achieved through cooperative interactions among chemoreceptors rather than through fine-tuning of methylation rates for individual receptors. This observation illustrates a yet-unrecognized function of receptor clustering in bacterial chemotaxis.

  16. Stress and adaptation responses to repeated acute acceleration.

    NASA Technical Reports Server (NTRS)

    Burton, R. R.; Smith, A. H.

    1972-01-01

    Study in which groups of adult male chickens (single-comb white leghorn) were exposed daily to acceleration (centrifugation) of 2 or 3 G for 10 min, 1, 4, 8, 12, 16, and 24 hr (continuously), or 0 time (controls). After approximately five months of this intermittent treatment (training), the birds were exposed to continuous accelerations of the same G force (intensity). The degree of stress and adaptation of each bird was determined by survival and relative lymphocyte count criteria. Intermittent training exposures of 2 G developed levels of adaptation in birds directly proportional to the duration of their daily exposure. Intermittent training periods at 3 G, however, produced a physiological deterioration in birds receiving daily exposures of 8 hr or more. Adaptive benefits were found only in the 1- and 4-hr-daily intermittent 3-G exposure groups. Exposure to 3 G produced an immediate stress response as indicated by a low relative lymphocyte count which returned to control (preexposed) values prior to the next daily acceleration period in the 10-min, 1-hr, and 4-hr groups. This daily recovery period from stress appeared to be necessary for adaptation as opposed to deterioration for the more severe environmental (3 G) alteration.

  17. Bayesian response-adaptive designs for basket trials.

    PubMed

    Ventz, Steffen; Barry, William T; Parmigiani, Giovanni; Trippa, Lorenzo

    2017-02-17

    We develop a general class of response-adaptive Bayesian designs using hierarchical models, and provide open source software to implement them. Our work is motivated by recent master protocols in oncology, where several treatments are investigated simultaneously in one or multiple disease types, and treatment efficacy is expected to vary across biomarker-defined subpopulations. Adaptive trials such as I-SPY-2 (Barker et al., 2009) and BATTLE (Zhou et al., 2008) are special cases within our framework. We discuss the application of our adaptive scheme to two distinct research goals. The first is to identify a biomarker subpopulation for which a therapy shows evidence of treatment efficacy, and to exclude other subpopulations for which such evidence does not exist. This leads to a subpopulation-finding design. The second is to identify, within biomarker-defined subpopulations, a set of cancer types for which an experimental therapy is superior to the standard-of-care. This goal leads to a subpopulation-stratified design. Using simulations constructed to faithfully represent ongoing cancer sequencing projects, we quantify the potential gains of our proposed designs relative to conventional non-adaptive designs.

  18. Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

    EPA Science Inventory

    Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

  19. Homeodomain Protein Otp and Activity-Dependent Splicing Modulate Neuronal Adaptation to Stress

    PubMed Central

    Amir-Zilberstein, Liat; Blechman, Janna; Sztainberg, Yehezkel; Norton, William H.J.; Reuveny, Adriana; Borodovsky, Nataliya; Tahor, Maayan; Bonkowsky, Joshua L.; Bally-Cuif, Laure; Chen, Alon; Levkowitz, Gil

    2015-01-01

    SUMMARY Regulation of corticotropin-releasing hormone (CRH) activity is critical for the animal’s adaptation to stressful challenges, and its dysregulation is associated with psychiatric disorders in humans. However, the molecular mechanism underlying this transcriptional response to stress is not well understood. Using various stress paradigms in mouse and zebrafish, we show that the hypothalamic transcription factor Orthopedia modulates the expression of CRH as well as the splicing factor Ataxin 2-Binding Protein-1 (A2BP1/Rbfox-1). We further show that the G protein coupled receptor PAC1, which is a known A2BP1/Rbfox-1 splicing target and an important mediator of CRH activity, is alternatively spliced in response to a stressful challenge. The generation of PAC1-hop messenger RNA isoform by alternative splicing is required for termination of CRH transcription, normal activation of the hypothalamic-pituitary-adrenal axis and adaptive anxiety-like behavior. Our study identifies an evolutionarily conserved biochemical pathway that modulates the neuronal adaptation to stress through transcriptional activation and alternative splicing. PMID:22284183

  20. Nutritional strategies to modulate the adaptive response to endurance training.

    PubMed

    Hawley, John A

    2013-01-01

    In recent years, advances in molecular biology have allowed scientists to elucidate how endurance exercise training stimulates skeletal muscle remodeling (i.e. promotes mitochondrial biogenesis). A growing field of interest directly arising from our understanding of the molecular bases of training adaptation is how nutrient availability can alter the regulation of many contraction-induced events in muscle in response to endurance exercise. Acutely manipulating substrate availability can exert profound effects on muscle energy stores and patterns of fuel metabolism during exercise, as well as many processes activating gene expression and cell signaling. Accordingly, such interventions when repeated over weeks and months have the potential to modulate numerous adaptive processes in skeletal muscle that ultimately drive the phenotype-specific characteristics observed in highly trained athletes. In this review, the molecular and cellular events that occur in skeletal muscle during and after endurance exercise are discussed and evidence provided to demonstrate that nutrient availability plays an important role in modulating many of the adaptive responses to training. Emphasis is on human studies that have determined the regulatory role of muscle glycogen availability on cell metabolism, endurance training capacity and performance.

  1. Stress Response and Perinatal Reprogramming: Unraveling (Mal)adaptive Strategies

    PubMed Central

    Musazzi, Laura; Marrocco, Jordan

    2016-01-01

    Environmental stressors induce coping strategies in the majority of individuals. The stress response, involving the activation of the hypothalamic-pituitary-adrenocortical axis and the consequent release of corticosteroid hormones, is indeed aimed at promoting metabolic, functional, and behavioral adaptations. However, behavioral stress is also associated with fast and long-lasting neurochemical, structural, and behavioral changes, leading to long-term remodeling of glutamate transmission, and increased susceptibility to neuropsychiatric disorders. Of note, early-life events, both in utero and during the early postnatal life, trigger reprogramming of the stress response, which is often associated with loss of stress resilience and ensuing neurobehavioral (mal)adaptations. Indeed, adverse experiences in early life are known to induce long-term stress-related neuropsychiatric disorders in vulnerable individuals. Here, we discuss recent findings about stress remodeling of excitatory neurotransmission and brain morphology in animal models of behavioral stress. These changes are likely driven by epigenetic factors that lie at the core of the stress-response reprogramming in individuals with a history of perinatal stress. We propose that reprogramming mechanisms may underlie the reorganization of excitatory neurotransmission in the short- and long-term response to stressful stimuli. PMID:27057367

  2. Immunoinhibitory adapter protein Src homology domain 3 lymphocyte protein 2 (SLy2) regulates actin dynamics and B cell spreading.

    PubMed

    von Holleben, Max; Gohla, Antje; Janssen, Klaus-Peter; Iritani, Brian M; Beer-Hammer, Sandra

    2011-04-15

    Appropriate B cell activation is essential for adaptive immunity. In contrast to the molecular mechanisms that regulate positive signaling in immune responses, the counterbalancing negative regulatory pathways remain insufficiently understood. The Src homology domain 3 (SH3)-containing adapter protein SH3 lymphocyte protein 2 (SLy2, also known as hematopoietic adapter-containing SH3 and sterile α-motif (SAM) domains 1; HACS1) is strongly up-regulated upon B cell activation and functions as an endogenous immunoinhibitor in vivo, but the underlying molecular mechanisms of SLy2 function have been elusive. We have generated transgenic mice overexpressing SLy2 in B and T cells and have studied the biological effects of elevated SLy2 levels in Jurkat and HeLa cells. Our results demonstrate that SLy2 induces Rac1-dependent membrane ruffle formation and regulates cell spreading and polarization and that the SLy2 SH3 domain is essential for these effects. Using immunoprecipitation and confocal microscopy, we provide evidence that the actin nucleation-promoting factor cortactin is an SH3 domain-directed interaction partner of SLy2. Consistent with an important role of SLy2 for actin cytoskeletal reorganization, we further show that SLy2-transgenic B cells are severely defective in cell spreading. Together, our findings extend our mechanistic understanding of the immunoinhibitory roles of SLy2 in vivo and suggest that the physiological up-regulation of SLy2 observed upon B cell activation functions to counteract excessive B cell spreading.

  3. Differential Adaptive Response and Survival of Salmonella enterica Serovar Enteritidis Planktonic and Biofilm Cells Exposed to Benzalkonium Chloride▿

    PubMed Central

    Mangalappalli-Illathu, Anil K.; Vidović, Sinisa; Korber, Darren R.

    2008-01-01

    This study examined the adaptive response and survival of planktonic and biofilm phenotypes of Salmonella enterica serovar Enteritidis adapted to benzalkonium chloride (BC). Planktonic cells and biofilms were continuously exposed to 1 μg ml−1 of BC for 144 h. The proportion of BC-adapted biofilm cells able to survive a lethal BC treatment (30 μg ml−1) was significantly higher (4.6-fold) than that of BC-adapted planktonic cells. Similarly, there were 18.3-fold more survivors among the BC-adapted biofilm cells than among their nonadapted (i.e., without prior BC exposure) cell counterparts at the lethal BC concentration, and this value was significantly higher than the value for BC-adapted planktonic cells versus nonadapted cells (3.2-fold). A significantly higher (P < 0.05) proportion of surviving cells was noticed among BC-adapted biofilm cells relative to BC-adapted planktonic cells following a 10-min heat shock at 55°C. Fatty acid composition was significantly influenced by phenotype (planktonic cells or biofilm) and BC adaptation. Cell surface roughness of biofilm cells was also significantly greater (P < 0.05) than that of planktonic cells. Key proteins upregulated in BC-adapted planktonic and biofilm cells included CspA, TrxA, Tsf, YjgF, and a probable peroxidase, STY0440. Nine and 17 unique proteins were upregulated in BC-adapted planktonic and biofilm cells, respectively. These results suggest that enhanced biofilm-specific upregulation of 17 unique proteins, along with the increased expression of CspA, TrxA, Tsf, YjgF, and a probable peroxidase, phenotype-specific alterations in cell surface roughness, and a shift in fatty acid composition conferred enhanced survival to the BC-adapted biofilm cell population relative to their BC-adapted planktonic cell counterparts. PMID:18663028

  4. Unfolded protein response in filamentous fungi-implications in biotechnology.

    PubMed

    Heimel, Kai

    2015-01-01

    The unfolded protein response (UPR) represents a mechanism to preserve endoplasmic reticulum (ER) homeostasis that is conserved in eukaryotes. ER stress caused by the accumulation of potentially toxic un- or misfolded proteins in the ER triggers UPR activation and the induction of genes important for protein folding in the ER, ER expansion, and transport from and to the ER. Along with this adaptation, the overall capacity for protein secretion is markedly increased by the UPR. In filamentous fungi, various approaches to employ the UPR for improved production of homologous and heterologous proteins have been investigated. As the effects on protein production were strongly dependent on the expressed protein, generally applicable strategies have to be developed. A combination of transcriptomic approaches monitoring secretion stress and basic research on the UPR mechanism provided novel and important insight into the complex regulatory cross-connections between UPR signalling, cellular physiology, and developmental processes. It will be discussed how this increasing knowledge on the UPR might stimulate the development of novel strategies for using the UPR as a tool in biotechnology.

  5. Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma

    PubMed Central

    Loilome, Watcharin; Kadsanit, Sasithorn; Muisook, Kanha; Yongvanit, Puangrat; Namwat, Nisana; Techasen, Anchalee; Puapairoj, Anucha; Khuntikeo, Narong; Phonjit, Pichai

    2017-01-01

    The adaptive response of the genome protection mechanism occurs in cells when exposed to genotoxic stress due to the overproduction of free radicals via inflammation and infection. In such circumstances, cells attempt to maintain health via several genome protection mechanisms. However, evidence is increasing that this adaptive response may have deleterious effect; a reduction of antioxidant enzymes and/or imbalance in the DNA repair system generates microsatellite instability (MSI), which has procarcinogenic implications. Therefore, the present study hypothesized that MSI caused by imbalanced responses of antioxidant enzymes and/or DNA repair enzymes as a result of oxidative/nitrative stress arising from the inflammatory response is involved in liver fluke-associated cholangiocarcinogenesis. The present study investigated this hypothesis by identifying the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), and DNA repair enzymes, including alkyladenine DNA glycosylase (AAG), apurinic endonuclease (APE) and DNA polymerase β (DNA pol β). In addition, the activities of the antioxidant enzymes, SOD2 and CAT, were examined in human cholangiocarcinoma (CCA) tissues using immunohistochemical staining. MSI was also analyzed in human CCA tissues. The resulting data demonstrated that the expression levels of the SOD2 and CAT enzymes decreased. The activities of SOD2 and CAT decreased significantly in the CCA tissues, compared with the hepatic tissue of cadaveric donors. In the DNA repairing enzymes, it was found that the expression levels of AAG and DNA pol β enzymes increased, whereas the expression of APE decreased. In addition, it was found that MSI-high was present in 69% of patients, whereas MSI-low was present in 31% of patients, with no patients classified as having microsatellite stability. In the patients, a MSI-high was correlated with poor prognosis, indicated by a shorter survival rate. These results

  6. The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Hardwick, Rhiannon N; Flores-Keown, Brieanna; Zhao, Fei; Klimecki, Walter T; Cherrington, Nathan J

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) may progress from simple steatosis to severe, nonalcoholic steatohepatitis (NASH) in 7%-14% of the U.S. population through a second "hit" in the form of increased oxidative stress and inflammation. Endoplasmic reticulum (ER) stress signaling and the unfolded protein response (UPR) are triggered when high levels of lipids and misfolded proteins alter ER homeostasis creating a lipotoxic environment within NAFLD livers. The objective of this study was to determine the coordinate regulation of ER stress-associated genes in the progressive stages of human NAFLD. Human liver samples categorized as normal, steatosis, NASH (Fatty), and NASH (Not Fatty) were analyzed by individual Affymetrix GeneChip Human 1.0 ST microarrays, immunoblots, and immunohistochemistry. A gene set enrichment analysis was performed on autophagy, apoptosis, lipogenesis, and ER stress/UPR gene categories. An enrichment of downregulated genes in the ER stress-associated lipogenesis and ER stress/UPR gene categories was observed in NASH. Conversely, an enrichment of upregulated ER stress-associated genes for autophagy and apoptosis gene categories was observed in NASH. Protein expression of the adaptive liver response protein STC2 and the transcription factor X-box binding protein 1 spliced (XBP-1s) were significantly elevated among NASH samples, whereas other downstream ER stress proteins including CHOP, ATF4, and phosphorylated JNK and eIF2α were not significantly changed in disease progression. Increased nuclear accumulation of total XBP-1 protein was observed in steatosis and NASH livers. The findings reveal the presence of a coordinated, adaptive transcriptional response to hepatic ER stress in human NAFLD.

  7. Response and adaptation of bone cells to simulated microgravity

    NASA Astrophysics Data System (ADS)

    Hu, Lifang; Li, Runzhi; Su, Peihong; Arfat, Yasir; Zhang, Ge; Shang, Peng; Qian, Airong

    2014-11-01

    Bone loss induced by microgravity during space flight is one of the most deleterious factors on astronaut's health and is mainly attributed to an unbalance in the process of bone remodeling. Studies from the space microgravity have demonstrated that the disruption of bone remodeling is associated with the changes of four main functional bone cells, including osteoblast, osteoclast, osteocyte, and mesenchymal stem cells. For the limited availability, expensive costs and confined experiment conditions for conducting space microgravity studies, the mechanism of bone cells response and adaptation to microgravity is still unclear. Therefore, some ground-based simulated microgravity methods have been developed to investigate the bioeffects of microgravity and the mechanisms. Here, based on our studies and others, we review how bone cells (osteoblasts, osteoclasts, osteocytes and mesenchymal stem cells) respond and adapt to simulated microgravity.

  8. Genome-wide transcriptional responses to a lipid hydroperoxide: adaptation occurs without induction of oxidant defenses.

    PubMed

    Alic, Nazif; Felder, Thomas; Temple, Mark D; Gloeckner, Christian; Higgins, Vincent J; Briza, Peter; Dawes, Ian W

    2004-07-01

    Free radicals can initiate the oxidation of polyunsaturated fatty acids in cells through the process of lipid peroxidation. The genome-wide transcriptional changes in Saccharomyces cerevisiae after treatment with the toxic lipid peroxidation product linoleic acid hydroperoxide (LoaOOH) were identified. High-dose treatment led to a switch in transcription from biosynthetic to protective functions. This response encompassed a set of genes stimulated predominantly by LoaOOH, and not by other oxidants or heat shock, which contained components of the pleiotropic drug resistance system. The dose dependence of the transcriptional response revealed that large and widespread changes occur only in response to higher doses. Pretreatment of cells with sublethal doses of LoaOOH induces resistance to an otherwise lethal dose through the process of adaptation. Adaptive doses elicited a more subtle transcriptional response affecting metabolic functions, including an increase in the capacity for detoxification and downregulation of the rate of protein synthesis. Surprisingly, the cellular response to adaptive doses did not include induction of oxidative-stress defense enzymes nor of transcripts involved in general cellular defense systems.

  9. Global Transcriptional, Physiological, and Metabolite Analyses of the Responses of Desulfovibrio vulgaris Hildenborough to Salt Adaptation ▿ †

    PubMed Central

    He, Zhili; Zhou, Aifen; Baidoo, Edward; He, Qiang; Joachimiak, Marcin P.; Benke, Peter; Phan, Richard; Mukhopadhyay, Aindrila; Hemme, Christopher L.; Huang, Katherine; Alm, Eric J.; Fields, Matthew W.; Wall, Judy; Stahl, David; Hazen, Terry C.; Keasling, Jay D.; Arkin, Adam P.; Zhou, Jizhong

    2010-01-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by performing physiological, global transcriptional, and metabolite analyses. Salt adaptation was reflected by increased expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). The expression of genes involved in carbon metabolism, cell growth, and phage structures was decreased. Transcriptome profiles of D. vulgaris responses to salt adaptation were compared with transcriptome profiles of D. vulgaris responses to salt shock (short-term NaCl exposure). Metabolite assays showed that glutamate and alanine accumulated under salt adaptation conditions, suggesting that these amino acids may be used as osmoprotectants in D. vulgaris. Addition of amino acids (glutamate, alanine, and tryptophan) or yeast extract to the growth medium relieved salt-related growth inhibition. A conceptual model that links the observed results to currently available knowledge is proposed to increase our understanding of the mechanisms of D. vulgaris adaptation to elevated NaCl levels. PMID:20038696

  10. Adaptive Patterns of Stress Responsivity: A Preliminary Investigation

    PubMed Central

    Del Giudice, Marco; Hinnant, J. Benjamin; Ellis, Bruce J.; El-Sheikh, Mona

    2014-01-01

    The adaptive calibration model (ACM) is an evolutionary–developmental theory of individual differences in stress responsivity. In this article, we tested some key predictions of the ACM in a middle childhood sample (N = 256). Measures of autonomic nervous system activity across the sympathetic and parasympathetic branches validated the 4-pattern taxonomy of the ACM via finite mixture modeling. Moreover, the 4 patterns of responsivity showed the predicted associations with family stress levels but no association with measures of ecological stress. Our hypotheses concerning sex differences in responsivity were only partly confirmed. This preliminary study provides initial support for the key predictions of the ACM and highlights some of the methodological challenges that will need to be considered in future research on this topic. PMID:22148947

  11. Plant adaptation to low atmospheric pressures: potential molecular responses.

    PubMed

    Ferl, Robert J; Schuerger, Andrew C; Paul, Anna-Lisa; Gurley, William B; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

  12. Plant adaptation to low atmospheric pressures: potential molecular responses

    NASA Technical Reports Server (NTRS)

    Ferl, Robert J.; Schuerger, Andrew C.; Paul, Anna-Lisa; Gurley, William B.; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

  13. Aeroelastic Response of the Adaptive Compliant Trailing Edge Transtition Section

    NASA Technical Reports Server (NTRS)

    Herrera, Claudia Y.; Spivey, Natalie D.; Lung, Shun-fat

    2016-01-01

    The Adaptive Compliant Trailing Edge demonstrator was a joint task under the Environmentally Responsible Aviation Project in partnership with the Air Force Research Laboratory and FlexSys, Inc. (Ann Arbor, Michigan), chartered by the National Aeronautics and Space Administration to develop advanced technologies that enable environmentally friendly aircraft, such as continuous mold-line technologies. The Adaptive Compliant Trailing Edge demonstrator encompassed replacing the Fowler flaps on the SubsoniC Aircraft Testbed, a Gulfstream III (Gulfstream Aerospace, Savannah, Georgia) aircraft, with control surfaces developed by FlexSys, Inc., a pair of uniquely-designed, unconventional flaps to be used as lifting surfaces during flight-testing to substantiate their structural effectiveness. The unconventional flaps consisted of a main flap section and two transition sections, inboard and outboard, which demonstrated the continuous mold-line technology. Unique characteristics of the transition sections provided a challenge to the airworthiness assessment for this part of the structure. A series of build-up tests and analyses were conducted to ensure the data required to support the airworthiness assessment were acquired and applied accurately. The transition sections were analyzed both as individual components and as part of the flight-test article assembly. Instrumentation was installed in the transition sections based on the analysis to best capture the in-flight aeroelastic response. Flight-testing was conducted and flight data were acquired to validate the analyses. This paper documents the details of the aeroelastic assessment and in-flight response of the transition sections of the unconventional Adaptive Compliant Trailing Edge flaps.

  14. Highly Precise Quantification of Protein Molecules per Cell During Stress and Starvation Responses in Bacillus subtilis *

    PubMed Central

    Maaβ, Sandra; Wachlin, Gerhild; Bernhardt, Jörg; Eymann, Christine; Fromion, Vincent; Riedel, Katharina; Becher, Dörte; Hecker, Michael

    2014-01-01

    Systems biology based on high quality absolute quantification data, which are mandatory for the simulation of biological processes, successively becomes important for life sciences. We provide protein concentrations on the level of molecules per cell for more than 700 cytosolic proteins of the Gram-positive model bacterium Bacillus subtilis during adaptation to changing growth conditions. As glucose starvation and heat stress are typical challenges in B. subtilis' natural environment and induce both, specific and general stress and starvation proteins, these conditions were selected as models for starvation and stress responses. Analyzing samples from numerous time points along the bacterial growth curve yielded reliable and physiologically relevant data suitable for modeling of cellular regulation under altered growth conditions. The analysis of the adaptational processes based on protein molecules per cell revealed stress-specific modulation of general adaptive responses in terms of protein amount and proteome composition. Furthermore, analysis of protein repartition during glucose starvation showed that biomass seems to be redistributed from proteins involved in amino acid biosynthesis to enzymes of the central carbon metabolism. In contrast, during heat stress most resources of the cell, namely those from amino acid synthetic pathways, are used to increase the amount of chaperones and proteases. Analysis of dynamical aspects of protein synthesis during heat stress adaptation revealed, that these proteins make up almost 30% of the protein mass accumulated during early phases of this stress. PMID:24878497

  15. Protein engineering reveals ancient adaptive replacements in isocitrate dehydrogenase

    PubMed Central

    Dean, Antony M.; Golding, G. Brian

    1997-01-01

    Evolutionary analysis indicates that eubacterial NADP-dependent isocitrate dehydrogenases (EC 1.1.1.42) first evolved from an NAD-dependent precursor about 3.5 billion years ago. Selection in favor of utilizing NADP was probably a result of niche expansion during growth on acetate, where isocitrate dehydrogenase provides 90% of the NADPH necessary for biosynthesis. Amino acids responsible for differing coenzyme specificities were identified from x-ray crystallographic structures of Escherichia coli isocitrate dehydrogenase and the distantly related Thermus thermophilus NAD-dependent isopropylmalate dehydrogenase. Site-directed mutagenesis at sites lining the coenzyme binding pockets has been used to invert the coenzyme specificities of both enzymes. Reconstructed ancestral sequences indicate that these replacements are ancestral. Hence the adaptive history of molecular evolution is amenable to experimental investigation. PMID:9096353

  16. Biological and Theoretical Studies of Adaptive Networks: The Conditioned Response.

    DTIC Science & Technology

    1992-06-30

    Eichenbaum , H. and Butter, C.M., The role of frontalcortex-reticular interactions in performance and extinction of Recordings of multiple-unit activity in...such a way that they are appropriate to the ’task demands’ imposed by training parameters (Levey and Martin , 1968). The main evidence for this adaptive...8217 Science 237, 1445-1452. 12. Levey, A. B. and Martin , I. (1968) ’Shape of the conditioned eyelid response,’ Psychological Review 75, 398-408. 13. Millenson

  17. Deciphering the Adaptive Immune Response to Ovarian Cancer

    DTIC Science & Technology

    2014-10-01

    Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis...Holt, Ph.D., John Webb Ph.D., Peter Watson, M.D. Title of Project: Deciphering the Adaptive Immune Response to Ovarian Cancer INTRODUCTION...Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER

  18. Innate and adaptive immune responses in neurodegeneration and repair.

    PubMed

    Amor, Sandra; Woodroofe, M Nicola

    2014-03-01

    Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders. The articles highlight the role of the traditional resident immune cell of the CNS - the microglia - as well as the role of other glia astrocytes and oligodendrocytes in immune responses and their interplay with other immune cells including, mast cells, T cells and B cells. Future research should lead to new discoveries which highlight targets for therapeutic interventions which may be applicable to a range of neurodegenerative diseases.

  19. Glycerol stress in Saccharomyces cerevisiae: Cellular responses and evolved adaptations.

    PubMed

    Mattenberger, Florian; Sabater-Muñoz, Beatriz; Hallsworth, John E; Fares, Mario A

    2017-03-01

    Glycerol synthesis is key to central metabolism and stress biology in Saccharomyces cerevisiae, yet the cellular adjustments needed to respond and adapt to glycerol stress are little understood. Here, we determined impacts of acute and chronic exposures to glycerol stress in S. cerevisiae. Glycerol stress can result from an increase of glycerol concentration in the medium due to the S. cerevisiae fermenting activity or other metabolic activities. Acute glycerol-stress led to a 50% decline in growth rate and altered transcription of more than 40% of genes. The increased genetic diversity in S. cerevisiae population, which had evolved in the standard nutrient medium for hundreds of generations, led to an increase in growth rate and altered transcriptome when such population was transferred to stressful media containing a high concentration of glycerol; 0.41 M (0.990 water activity). Evolution of S. cerevisiae populations during a 10-day period in the glycerol-containing medium led to transcriptome changes and readjustments to improve control of glycerol flux across the membrane, regulation of cell cycle, and more robust stress response; and a remarkable increase of growth rate under glycerol stress. Most of the observed regulatory changes arose in duplicated genes. These findings elucidate the physiological mechanisms, which underlie glycerol-stress response, and longer-term adaptations, in S. cerevisiae; they also have implications for enigmatic aspects of the ecology of this otherwise well-characterized yeast.

  20. Adaptation response of Arabidopsis thaliana to random positioning

    NASA Astrophysics Data System (ADS)

    Kittang, A.-I.; Winge, P.; van Loon, J. J. W. A.; Bones, A. M.; Iversen, T.-H.

    2013-10-01

    Arabidopsis thaliana seedlings were exposed on a Random Positioning Machine (RPM) under light conditions for 16 h and the samples were analysed using microarray techniques as part of a preparation for a space experiment on the International Space Station (ISS). The results demonstrated a moderate to low regulation of 55 genes (<0.2% of the analysed genes). Genes encoding proteins associated with the chaperone system (e.g. heat shock proteins, HSPs) and enzymes in the flavonoid biosynthesis were induced. Most of the repressed genes were associated with light and sugar responses. Significant up-regulation of selected HSP genes was found by quantitative Real-Time PCR in 1 week old plants after the RPM exposure both in light and darkness. Higher quantity of DPBA (diphenylboric acid 2-amino-ethyl ester) staining was observed in the whole root and in the root elongation zone of the seedlings exposed on the RPM by use of fluorescent microscopy, indicating higher flavonoid content. The regulated genes and an increase of flavonoids are related to several stresses, but increased occurrence of HSPs and flavonoids are also representative for normal growth (e.g. gravitropism). The response could be a direct stress response or an integrated response of the two signal pathways of light and gravity resulting in an overall light response.

  1. Aggresomes: A Cellular Response to Misfolded Proteins

    PubMed Central

    Johnston, Jennifer A.; Ward, Cristina L.; Kopito, Ron R.

    1998-01-01

    Intracellular deposition of misfolded protein aggregates into ubiquitin-rich cytoplasmic inclusions is linked to the pathogenesis of many diseases. Why these aggregates form despite the existence of cellular machinery to recognize and degrade misfolded protein and how they are delivered to cytoplasmic inclusions are not known. We have investigated the intracellular fate of cystic fibrosis transmembrane conductance regulator (CFTR), an inefficiently folded integral membrane protein which is degraded by the cytoplasmic ubiquitin-proteasome pathway. Overexpression or inhibition of proteasome activity in transfected human embryonic kidney or Chinese hamster ovary cells led to the accumulation of stable, high molecular weight, detergent-insoluble, multiubiquitinated forms of CFTR. Using immunofluorescence and transmission electron microscopy with immunogold labeling, we demonstrate that undegraded CFTR molecules accumulate at a distinct pericentriolar structure which we have termed the aggresome. Aggresome formation is accompanied by redistribution of the intermediate filament protein vimentin to form a cage surrounding a pericentriolar core of aggregated, ubiquitinated protein. Disruption of microtubules blocks the formation of aggresomes. Similarly, inhibition of proteasome function also prevented the degradation of unassembled presenilin-1 molecules leading to their aggregation and deposition in aggresomes. These data lead us to propose that aggresome formation is a general response of cells which occurs when the capacity of the proteasome is exceeded by the production of aggregation-prone misfolded proteins. PMID:9864362

  2. Effects of protein conformation in docking: improved pose prediction through protein pocket adaptation

    NASA Astrophysics Data System (ADS)

    Jain, Ajay N.

    2009-06-01

    Computational methods for docking ligands have been shown to be remarkably dependent on precise protein conformation, where acceptable results in pose prediction have been generally possible only in the artificial case of re-docking a ligand into a protein binding site whose conformation was determined in the presence of the same ligand (the "cognate" docking problem). In such cases, on well curated protein/ligand complexes, accurate dockings can be returned as top-scoring over 75% of the time using tools such as Surflex-Dock. A critical application of docking in modeling for lead optimization requires accurate pose prediction for novel ligands, ranging from simple synthetic analogs to very different molecular scaffolds. Typical results for widely used programs in the "cross-docking case" (making use of a single fixed protein conformation) have rates closer to 20% success. By making use of protein conformations from multiple complexes, Surflex-Dock yields an average success rate of 61% across eight pharmaceutically relevant targets. Following docking, protein pocket adaptation and rescoring identifies single pose families that are correct an average of 67% of the time. Consideration of the best of two pose families (from alternate scoring regimes) yields a 75% mean success rate.

  3. Effects of protein conformation in docking: improved pose prediction through protein pocket adaptation.

    PubMed

    Jain, Ajay N

    2009-06-01

    Computational methods for docking ligands have been shown to be remarkably dependent on precise protein conformation, where acceptable results in pose prediction have been generally possible only in the artificial case of re-docking a ligand into a protein binding site whose conformation was determined in the presence of the same ligand (the "cognate" docking problem). In such cases, on well curated protein/ligand complexes, accurate dockings can be returned as top-scoring over 75% of the time using tools such as Surflex-Dock. A critical application of docking in modeling for lead optimization requires accurate pose prediction for novel ligands, ranging from simple synthetic analogs to very different molecular scaffolds. Typical results for widely used programs in the "cross-docking case" (making use of a single fixed protein conformation) have rates closer to 20% success. By making use of protein conformations from multiple complexes, Surflex-Dock yields an average success rate of 61% across eight pharmaceutically relevant targets. Following docking, protein pocket adaptation and rescoring identifies single pose families that are correct an average of 67% of the time. Consideration of the best of two pose families (from alternate scoring regimes) yields a 75% mean success rate.

  4. Response and adaptation of Beagle dogs to hypergravity

    NASA Technical Reports Server (NTRS)

    Oyama, J.

    1975-01-01

    Eight male Beagle dogs, five months old, were centrifuged continuously for three months at progressively increasing loads. Heart rate and deep body temperature were monitored continuously by implant biotelemetry. Initially, centrifuged dogs showed transient decreases in heart rate and body temperature along with changes in their diurnal rhythm patterns. Compared with normal gravity controls, exposed dogs showed a slower growth rate and a reduced amount of body fat. Blood protein, total lipids, cholesterol, calcium, packed cell volume, red blood cell count, and hemoglobin were also decreased significantly. Absolute weights of the leg bones of centrifuged dogs were significantly greater than controls. Photon absorptiometry revealed significant density increases in selective regions of the femur and humerus of centrifuged dogs. In spite of the various changes noted, results from this and other studies affirm the view that dogs can tolerate and adapt to sustained loads as high as 2.5 g without serious impairment of their body structure and function.

  5. Chlamydia trachomatis: Protective Adaptive Responses and Prospects for a Vaccine.

    PubMed

    Poston, Taylor B; Darville, Toni

    2016-04-01

    Chlamydia trachomatis is the most common cause of sexually transmitted bacterial infection globally. These infections translate to a significant public health burden, particularly women's healthcare costs due to serious disease sequelae such as pelvic inflammatory disease (PID), tubal factor infertility, chronic pelvic pain, and ectopic pregnancy. There is no evidence that natural immunity can provide complete, long-term protection necessary to prevent chronic pathology, making human vaccine development critical. Vaccine design will require careful consideration of protective versus pathological host-response mechanisms in concert with elucidation of optimal antigens and adjuvants. Evidence suggests that a Th1 response, facilitated by IFN-γ-producing CD4 T cells, will be instrumental in generating long-term, sterilizing immunity. Although the role of antibodies is not completely understood, they have exhibited a protective effect by enhancing chlamydial clearance. Future work will require investigation of broadly neutralizing antibodies and antibody-augmented cellular immunity to successfully design a vaccine that potently elicits both arms of the immune response. Sterilizing immunity is the ultimate goal. However, vaccine-induced partial immunity that prevents upper genital tract infection and inflammation would be cost-effective compared to current screening and treatment strategies. In this chapter, we examine evidence from animal and human studies demonstrating protective adaptive immune responses to Chlamydia and discuss future challenges and prospects for vaccine development.

  6. Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer.

    PubMed

    Eritja, Núria; Chen, Bo-Juen; Rodríguez-Barrueco, Ruth; Santacana, Maria; Gatius, Sònia; Vidal, August; Martí, Maria Dolores; Ponce, Jordi; Bergadà, Laura; Yeramian, Andree; Encinas, Mario; Ribera, Joan; Reventós, Jaume; Boyd, Jeff; Villanueva, Alberto; Matias-Guiu, Xavier; Dolcet, Xavier; Llobet-Navàs, David

    2017-01-05

    Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma. Unfortunately, sorafenib showed very modest effects in a multi-institutional phase II trial in advanced uterine carcinoma patients. Here, by leveraging RNA-sequencing data from the Cancer Cell Line Encyclopedia and cell survival studies from compound-based high-throughput screenings we have identified the lysosomal pathway as a potential compartment involved in the resistance to sorafenib. By performing additional functional biology studies we have demonstrated that this resistance could be related to macroautophagy/autophagy. Specifically, our results indicate that sorafenib triggers a mechanistic MAPK/JNK-dependent early protective autophagic response in EC cells, providing an adaptive response to therapeutic stress. By generating in vivo subcutaneous EC cell line tumors, lung metastatic assays and primary EC orthoxenografts experiments, we demonstrate that targeting autophagy enhances sorafenib cytotoxicity and suppresses tumor growth and pulmonary metastasis progression. In conclusion, sorafenib induces the activation of a protective autophagic response in EC cells. These results provide insights into the unopposed resistance of advanced EC to sorafenib and highlight a new strategy for therapeutic intervention in recurrent EC.

  7. PD-1 blockade induces responses by inhibiting adaptive immune resistance

    PubMed Central

    Tumeh, Paul C.; Harview, Christina L.; Yearley, Jennifer H.; Shintaku, I. Peter; Taylor, Emma J. M.; Robert, Lidia; Chmielowski, Bartosz; Spasic, Marko; Henry, Gina; Ciobanu, Voicu; West, Alisha N.; Carmona, Manuel; Kivork, Christine; Seja, Elizabeth; Cherry, Grace; Gutierrez, Antonio; Grogan, Tristan R.; Mateus, Christine; Tomasic, Gorana; Glaspy, John A.; Emerson, Ryan O.; Robins, Harlan; Pierce, Robert H.; Elashoff, David A.; Robert, Caroline; Ribas, Antoni

    2014-01-01

    Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types.1–5 One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8 T-cells (termed adaptive immune resistance).6,7 Here we show that pre-existing CD8 T-cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analyzed samples from 46 patients with metastatic melanoma obtained before and during anti-PD1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next generation sequencing for T-cell receptors (TCR). In serially sampled tumours, responding patients showed proliferation of intratumoural CD8+ T-cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8, PD1, and PD-L1 expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression following therapeutic PD-1 blockade requires pre-existing CD8+ T cells that are negatively regulated by PD-1/PD-L1 mediated adaptive immune resistance. PMID:25428505

  8. Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer

    PubMed Central

    Eritja, Núria; Chen, Bo-Juen; Rodríguez-Barrueco, Ruth; Santacana, Maria; Gatius, Sònia; Vidal, August; Martí, Maria Dolores; Ponce, Jordi; Bergadà, Laura; Yeramian, Andree; Encinas, Mario; Ribera, Joan; Reventós, Jaume; Boyd, Jeff; Villanueva, Alberto; Matias-Guiu, Xavier; Dolcet, Xavier

    2017-01-01

    ABSTRACT Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma. Unfortunately, sorafenib showed very modest effects in a multi-institutional phase II trial in advanced uterine carcinoma patients. Here, by leveraging RNA-sequencing data from the Cancer Cell Line Encyclopedia and cell survival studies from compound-based high-throughput screenings we have identified the lysosomal pathway as a potential compartment involved in the resistance to sorafenib. By performing additional functional biology studies we have demonstrated that this resistance could be related to macroautophagy/autophagy. Specifically, our results indicate that sorafenib triggers a mechanistic MAPK/JNK-dependent early protective autophagic response in EC cells, providing an adaptive response to therapeutic stress. By generating in vivo subcutaneous EC cell line tumors, lung metastatic assays and primary EC orthoxenografts experiments, we demonstrate that targeting autophagy enhances sorafenib cytotoxicity and suppresses tumor growth and pulmonary metastasis progression. In conclusion, sorafenib induces the activation of a protective autophagic response in EC cells. These results provide insights into the unopposed resistance of advanced EC to sorafenib and highlight a new strategy for therapeutic intervention in recurrent EC. PMID:28055301

  9. Innate and Adaptive Immune Response to Apoptotic Cells

    PubMed Central

    Peng, YuFeng; Martin, David A; Kenkel, Justin; Zhang, Kang; Ogden, Carol Anne; Elkon, Keith B.

    2007-01-01

    The immune system is constantly exposed to dying cells, most of which arise during central tolerance and from effete circulating immune cells. Under homeostatic conditions, phagocytes (predominantly macrophages and dendritic cells) belonging to the innate immune system, rapidly ingest cells and their debris. Apoptotic cell removal requires recognition of altered self on the apoptotic membrane, a process which is facilitated by natural antibodies and serum opsonins. Recognition, may be site and context specific. Uptake and ingestion of apoptotic cells promotes an immunosuppressive environment that avoids inflammatory responses to self antigens. However, it does not preclude a T cell response and it is likely that constant exposure to self antigen, particularly by immature dendritic cells, leads to T cell tolerance. Tolerance occurs by several different mechanisms including anergy and deletion (for CD8+ T cells) and induction of T regulatory cells (for CD4+ T cells). Failed apoptotic cell clearance promotes immune responses to self antigens, especially when the cellular contents are leaked from the cell (necrosis). Inflammatory responses may be induced by nucleic acid stimulation of toll like receptors and other immune sensors, specific intracellular proteins and non protein (uric acid) stimulation of inflammasomes. PMID:17888627

  10. Innate and adaptive immune responses against Staphylococcus aureus skin infections.

    PubMed

    Krishna, Sheila; Miller, Lloyd S

    2012-03-01

    Staphylococcus aureus is an important human pathogen that is responsible for the vast majority of bacterial skin and soft tissue infections in humans. S. aureus can also become more invasive and cause life-threatening infections such as bacteremia, pneumonia, abscesses of various organs, meningitis, osteomyelitis, endocarditis, and sepsis. These infections represent a major public health threat due to the enormous numbers of these infections and the widespread emergence of methicillin-resistant S. aureus (MRSA) strains. MSRA is endemic in hospitals worldwide and is rapidly spreading throughout the normal human population in the community. The increasing frequency of MRSA infections has complicated treatment as these strains are more virulent and are increasingly becoming resistant to multiple different classes of antibiotics. The important role of the immune response against S. aureus infections cannot be overemphasized as humans with certain genetic and acquired immunodeficiency disorders are at an increased risk for infection. Understanding the cutaneous immune responses against S. aureus is essential as most of these infections occur or originate from a site of infection or colonization of the skin and mucosa. This review will summarize the innate immune responses against S. aureus skin infections, including antimicrobial peptides that have direct antimicrobial activity against S. aureus as well as pattern recognition receptors and proinflammatory cytokines that promote neutrophil abscess formation in the skin, which is required for bacterial clearance. Finally, we will discuss the recent discoveries involving IL-17-mediated responses, which provide a key link between cutaneous innate and adaptive immune responses against S. aureus skin infections.

  11. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

    PubMed

    Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  12. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework

    SciTech Connect

    Calabrese, Edward J. . E-mail: edwardc@schoolph.umass.edu; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  13. Development and Standardization of the Diagnostic Adaptive Behavior Scale: Application of Item Response Theory to the Assessment of Adaptive Behavior

    ERIC Educational Resources Information Center

    Tassé, Marc J.; Schalock, Robert L.; Thissen, David; Balboni, Giulia; Bersani, Henry, Jr.; Borthwick-Duffy, Sharon A.; Spreat, Scott; Widaman, Keith F.; Zhang, Dalun; Navas, Patricia

    2016-01-01

    The Diagnostic Adaptive Behavior Scale (DABS) was developed using item response theory (IRT) methods and was constructed to provide the most precise and valid adaptive behavior information at or near the cutoff point of making a decision regarding a diagnosis of intellectual disability. The DABS initial item pool consisted of 260 items. Using IRT…

  14. Osmotic pressure-adaptive responses in the eye tissues of rainbow smelt (Osmerus mordax)

    PubMed Central

    Armstrong, Elizabeth; Paradis, Hélène; Haines, Lacey; Desjardins, Mariève; Short, Connie E.; Clow, Kathy A.; Driedzic, William R.

    2011-01-01

    Purpose The rainbow smelt (Osmerus mordax), is a teleost fish, which avoids freezing by becoming virtually isosmotic with seawater. The effects that such massive changes in osmolarity have on both its visual system and its highly evolved and specialized circulation are not known. New knowledge about the osmotic adaptation of the rainbow smelt eye is highly relevant to the adaptation and survival of this species and to its ability to feed as a visual predator in the face of environmental pressures. Moreover, the molecular physiologic response of the smelt to osmotic stress might provide valuable insights into understanding and managing mammalian pathological hyperosmolarity conditions, such as diabetes. We undertook the present study to provide an initial assessment of gene expression in ocular vasculature during osmotic adaptation in rainbow smelt. Methods Immunohistochemistry with species cross reactive antibodies was used to assess blood vessel protein expression in paraffin sections. Western blotting was used to further verify antibody specificity for orthologs of mammalian blood vessel proteins in rainbow smelt. Thermal hysteresis and the analysis of glycerol concentrations in vitreous fluid were used to assess the physiologic adaptive properties of cold stressed eyes. Results Glycerol levels and osmotic pressure were significantly increased in the vitreal fluid of smelt maintained at <0.5 °C versus those maintained at 8–10 °C. Compared to the 8–10 °C adapted specimens, the rete mirabile blood vessels and connecting regions of the endothelial linings of the choroidal vessels of the <0.5 °C adapted specimens showed a higher expression level of Tubedown (Tbdn) protein, a marker of the endothelial transcellular permeability pathway. Expression of the zonula occludens protein ZO-1, a marker of the endothelial paracellular permeability pathway showed a reciprocal expression pattern and was downregulated in rete mirabile blood vessels and connecting

  15. Protein Degradation and the Stress Response

    PubMed Central

    Flick, Karin; Kaiser, Peter

    2012-01-01

    Environmental stresses are manifold and so are the responses they elicit. This is particularly true for higher eukaryotes where various tissues and cell types are differentially affected by the insult. Type and scope of the stress response can therefore differ greatly among cell types. Given the importance of the Ubiquitin Proteasome System (UPS) for most cellular processes, it comes as no surprise that the UPR plays a pivotal role in counteracting the effects of stressors. Here we outline contributions of the UPS to stress sensing, signaling, and response pathways. We make no claim to comprehensiveness but choose selected examples to illustrate concepts and mechanisms by which protein modification with ubiquitin and proteasomal degradation of key regulators ensures cellular integrity during stress situations. PMID:22414377

  16. The unfolded protein response has a protective role in yeast models of classic galactosemia.

    PubMed

    De-Souza, Evandro A; Pimentel, Felipe S A; Machado, Caio M; Martins, Larissa S; da-Silva, Wagner S; Montero-Lomelí, Mónica; Masuda, Claudio A

    2014-01-01

    Classic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast), which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia: lithium-treated cells and the gal7Δ mutant. The synthesis of galactose-1-phosphate is essential to trigger the unfolded protein response under these conditions because the deletion of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein response activation and galactose toxicity. Impairment of the unfolded protein response in both yeast models makes cells even more sensitive to galactose, unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum stress is induced under galactosemic conditions and underscores the importance of the unfolded protein response pathway to cellular adaptation in these models of classic galactosemia.

  17. The Inhibitor of Apoptosis (IAPs) in Adaptive Response to Cellular Stress

    PubMed Central

    Marivin, Arthur; Berthelet, Jean; Plenchette, Stéphanie; Dubrez, Laurence

    2012-01-01

    Cells are constantly exposed to endogenous and exogenous cellular injuries. They cope with stressful stimuli by adapting their metabolism and activating various “guardian molecules.” These pro-survival factors protect essential cell constituents, prevent cell death, and possibly repair cellular damages. The Inhibitor of Apoptosis (IAPs) proteins display both anti-apoptotic and pro-survival properties and their expression can be induced by a variety of cellular stress such as hypoxia, endoplasmic reticular stress and DNA damage. Thus, IAPs can confer tolerance to cellular stress. This review presents the anti-apoptotic and survival functions of IAPs and their role in the adaptive response to cellular stress. The involvement of IAPs in human physiology and diseases in connection with a breakdown of cellular homeostasis will be discussed. PMID:24710527

  18. Growth responses and adaptations of Fraxinus pennsylvanica seedlings to flooding

    SciTech Connect

    Sena Gomes, A.R.; Kozlowski, T.T.

    1980-01-01

    Flooding induced several physiological and morphological changes in Fraxinus pennsylvanica seedlings, with stomatal closure among the earliest responses. Subsequent changes included: reduction in dry weight increment of roots, stems, and leaves; formation of hypertrophied lenticles and production of adventitious roots on submerged portions of the stem above the soil line; leaf necrosis; and leaf abscission. After 15 days of stomatal closure as a results of flooding, stomata began to reopen progressively until stomata aperture was similar in flooded and unflooded plants. Adventitious roots began to form at about the time stomatal reopening began. As more adventitious roots formed, elongated, and branched, the stomata opened further. The formation of adventitious roots was in important adaptation for flooding tolerance as shown by the high efficiency of adventitious roots in absorption of water and in high correlation between the production of adventitious roots and stomatal reopening. 6 figures, 2 tables.

  19. Development and Standardization of the Diagnostic Adaptive Behavior Scale: Application of Item Response Theory to the Assessment of Adaptive Behavior.

    PubMed

    Tassé, Marc J; Schalock, Robert L; Thissen, David; Balboni, Giulia; Bersani, Henry Hank; Borthwick-Duffy, Sharon A; Spreat, Scott; Widaman, Keith F; Zhang, Dalun; Navas, Patricia

    2016-03-01

    The Diagnostic Adaptive Behavior Scale (DABS) was developed using item response theory (IRT) methods and was constructed to provide the most precise and valid adaptive behavior information at or near the cutoff point of making a decision regarding a diagnosis of intellectual disability. The DABS initial item pool consisted of 260 items. Using IRT modeling and a nationally representative standardization sample, the item set was reduced to 75 items that provide the most precise adaptive behavior information at the cutoff area determining the presence or not of significant adaptive behavior deficits across conceptual, social, and practical skills. The standardization of the DABS is described and discussed.

  20. Protein response to ligation reactions in myoglobin

    SciTech Connect

    Causgrove, T.P.; Dyer, R.B.

    1992-01-01

    The protein response to the photodissociation, escape and subsequent rebinding of carbon monoxide in myoglobin is studied using time-resolved infrared (TRIR) spectroscopy. All phases of these reactions areinvestigated, from ultrafast phenomena (picoseconds) to relatively slow processes (milliseconds). Conformational changes in myoglobin (Mb) are detected by time-resolved absorption changes in the amide I band. On the hundreds of nanoseconds to milliseconds timescale, a real-time'' apparatus is used. This apparatus is based on a tunable diode laser operating in the region of 1650 cm[sup [minus]1] . The time course ofchanges in the amide I band are shown to follow the recombination of CO with photolyzed Mb. On the basis of the rise times of the amide I and FE-CO signals, it is concluded that protein motion is complete within 100 n. A time-resolved difference spectrum in the amide I region is generated from single wavelength transients taken throughout the amide I envelope. A static difference spectrum is also generated by subtracting FTIR spectra of carbonmonoxy and deoxy myoglobin. The two difference spectra are compared and are interpreted in terms of the three-dimensional structures of deoxy and carbonmonoxy Mb. Preliminary picosecond TRIR data are also given for the ultrafast response of the protein immediately following photodissociation of CO.

  1. Protein response to ligation reactions in myoglobin

    SciTech Connect

    Causgrove, T.P.; Dyer, R.B.

    1992-12-31

    The protein response to the photodissociation, escape and subsequent rebinding of carbon monoxide in myoglobin is studied using time-resolved infrared (TRIR) spectroscopy. All phases of these reactions areinvestigated, from ultrafast phenomena (picoseconds) to relatively slow processes (milliseconds). Conformational changes in myoglobin (Mb) are detected by time-resolved absorption changes in the amide I band. On the hundreds of nanoseconds to milliseconds timescale, a ``real-time`` apparatus is used. This apparatus is based on a tunable diode laser operating in the region of 1650 cm{sup {minus}1} . The time course ofchanges in the amide I band are shown to follow the recombination of CO with photolyzed Mb. On the basis of the rise times of the amide I and FE-CO signals, it is concluded that protein motion is complete within 100 n. A time-resolved difference spectrum in the amide I region is generated from single wavelength transients taken throughout the amide I envelope. A static difference spectrum is also generated by subtracting FTIR spectra of carbonmonoxy and deoxy myoglobin. The two difference spectra are compared and are interpreted in terms of the three-dimensional structures of deoxy and carbonmonoxy Mb. Preliminary picosecond TRIR data are also given for the ultrafast response of the protein immediately following photodissociation of CO.

  2. Protein response to ligation reactions in myoglobin

    NASA Astrophysics Data System (ADS)

    Causgrove, Timothy P.; Dyer, R. B.

    1993-05-01

    The protein response to the photodissociation, escape and subsequent rebinding of carbon monoxide in myoglobin is studied using time-resolved infrared (TRIR) spectroscopy. All phases of these reactions are investigated, from ultrafast phenomena (picoseconds) to relatively slow processes (milliseconds). Conformational changes in myoglobin (Mb) are detected by time-resolved infrared absorption changes in the amide I band. On the hundreds of nanoseconds to milliseconds timescale, a 'real-time' apparatus is used. This apparatus is based on a tunable diode laser operating in the region of 1650 cm-1. The time course of changes in the amide I band are shown to follow the recombination of CO with photolyzed Mb. On the basis of the rise times of the amide I and Fe-CO signals, it is concluded that protein motion is complete within 100 ns. A time-resolved difference spectrum in the amide I region is generated from single wavelength transients taken throughout the amide I envelope. A static difference spectrum is also generated by subtracting FTIR spectra of carbonmonoxy and deoxy myoglobin. The two difference spectra are compared and are interpreted in terms of the three-dimensional structures of deoxy and carbonmonoxy Mb. Preliminary picosecond TRIR data are also given for the ultrafast response of the protein immediately following photodissociation of CO.

  3. Optimization of biguanide derivatives as selective antitumor agents blocking adaptive stress responses in the tumor microenvironment

    PubMed Central

    Narise, Kosuke; Okuda, Kensuke; Enomoto, Yukihiro; Hirayama, Tasuku; Nagasawa, Hideko

    2014-01-01

    Adaptive cellular responses resulting from multiple microenvironmental stresses, such as hypoxia and nutrient deprivation, are potential novel drug targets for cancer treatment. Accordingly, we focused on developing anticancer agents targeting the tumor microenvironment (TME). In this study, to search for selective antitumor agents blocking adaptive responses in the TME, thirteen new compounds, designed and synthesized on the basis of the arylmethylbiguanide scaffold of phenformin, were used in structure activity relationship studies of inhibition of hypoxia inducible factor (HIF)-1 and unfolded protein response (UPR) activation and of selective cytotoxicity under glucose-deprived stress conditions, using HT29 cells. We conducted luciferase reporter assays using stable cell lines expressing either an HIF-1-responsive reporter gene or a glucose-regulated protein 78 promoter-reporter gene, which were induced by hypoxia and glucose deprivation stress, respectively, to screen for TME-targeting antitumor drugs. The guanidine analog (compound 2), obtained by bioisosteric replacement of the biguanide group, had activities comparable with those of phenformin (compound 1). Introduction of various substituents on the phenyl ring significantly affected the activities. In particular, the o-methylphenyl analog compound 7 and the o-chlorophenyl analog compound 12 showed considerably more potent inhibitory effects on HIF-1 and UPR activation than did phenformin, and excellent selective cytotoxicity under glucose deprivation. These compounds, therefore, represent an improvement over phenformin. They also suppressed HIF-1- and UPR-related protein expression and secretion of vascular endothelial growth factor-A. Moreover, these compounds exhibited significant antiangiogenic effects in the chick chorioallantoic membrane assay. Our structural development studies of biguanide derivatives provided promising candidates for a novel anticancer agent targeting the TME for selective cancer

  4. Immunofluorescence Imaging of DNA Damage Response Proteins

    PubMed Central

    Bennett, Brian T.; Bewersdorf, Jörg; Knight, Kendall L.

    2013-01-01

    Immunofluorescence imaging has provided captivating visual evidence for numerous cellular events, from vesicular trafficking, organelle maturation and cell division to nuclear processes including the appearance of various proteins and chromatin components in distinct foci in response to DNA damaging agents. With the advent of new super-resolution microscope technologies such as 4Pi microscopy, standard immunofluorescence protocols deserve some reevaluation in order to take full advantage of these new technological accomplishments. Here we describe several methodological considerations that will help overcome some of the limitations that may result from the use of currently applied procedures, with particular attention paid to the analysis of possible colocalization of fluorescent signals. We conclude with an example of how application of optimized methods led to a breakthrough in super-resolution imaging of nuclear events occurring in response to DNA damage. PMID:19245833

  5. Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL.

    PubMed

    Sengupta, Dola; Koblansky, Alicia; Gaines, Jennifer; Brown, Tim; West, A Phillip; Zhang, Dekai; Nishikawa, Tak; Park, Sung-Gyoo; Roop, R Martin; Ghosh, Sankar

    2010-01-15

    Gram-negative bacteria belonging to the Brucella species cause chronic infections that can result in undulant fever, arthritis, and osteomyelitis in humans. Remarkably, Brucella sp. genomes encode a protein, named TcpB, that bears significant homology with mammalian Toll/IL-1 receptor domains and whose expression causes degradation of the phosphorylated, signal competent form of the adapter MyD88-adapter-like (MAL). This effect of TcpB is mediated through its box 1 region and has no effect on other TLR adapter proteins such as MyD88 or TIR-domain containing adapter protein-inducing IFNbeta. TcpB also does not affect a mutant, signal-incompetent form of MAL that cannot be phosphorylated. Interestingly, the presence of TcpB leads to enhanced polyubiquitination of MAL, which is likely responsible for its accelerated degradation. A Brucella abortus mutant lacking TcpB fails to reduce levels of MAL in infected macrophages. Therefore, TcpB represents a unique pathogen-derived molecule that suppresses host innate-immune responses by specifically targeting an individual adapter molecule in the TLR signaling pathway for degradation.

  6. Discovery of Sulfonamidebenzamides as Selective Apoptotic CHOP Pathway Activators of the Unfolded Protein Response

    PubMed Central

    2014-01-01

    Cellular proteins that fail to fold properly result in inactive or disfunctional proteins that can have toxic functions. The unfolded protein response (UPR) is a two-tiered cellular mechanism initiated by eukaryotic cells that have accumulated misfolded proteins within the endoplasmic reticulum (ER). An adaptive pathway facilitates the clearance of the undesired proteins; however, if overwhelmed, cells trigger apoptosis by upregulating transcription factors such as C/EBP-homologous protein (CHOP). A high throughput screen was performed directed at identifying compounds that selectively upregulate the apoptotic CHOP pathway while avoiding adaptive signaling cascades, resulting in a sulfonamidebenzamide chemotype that was optimized. These efforts produced a potent and selective CHOP inducer (AC50 = 0.8 μM; XBP1 > 80 μM), which was efficacious in both mouse embryonic fibroblast cells and a human oral squamous cell cancer cell line, and demonstrated antiproliferative effects for multiple cancer cell lines in the NCI-60 panel. PMID:25530830

  7. Muscle protein synthesis in response to nutrition and exercise.

    PubMed

    Atherton, P J; Smith, K

    2012-03-01

    Muscle protein synthesis (MPS) is the driving force behind adaptive responses to exercise and represents a widely adopted proxy for gauging chronic efficacy of acute interventions, (i.e. exercise/nutrition). Recent findings in this arena have been progressive. Nutrient-driven increases in MPS are of finite duration (∼1.5 h), switching off thereafter despite sustained amino acid availability and intramuscular anabolic signalling. Intriguingly, this 'muscle-full set-point' is delayed by resistance exercise (RE) (i.e. the feeding × exercise combination is 'more anabolic' than nutrition alone) even 24 h beyond a single exercise bout, casting doubt on the importance of nutrient timing vs. sufficiency per se. Studies manipulating exercise intensity/workload have shown that increases in MPS are negligible with RE at 20-40% but maximal at 70-90% of one-repetition maximum when workload is matched (according to load × repetition number). However, low-intensity exercise performed to failure equalises this response. Analysing distinct subcellular fractions (e.g. myofibrillar, sarcoplasmic, mitochondrial) may provide a readout of chronic exercise efficacy in addition to effect size in MPS per se, i.e. while 'mixed' MPS increases similarly with endurance and RE, increases in myofibrillar MPS are specific to RE, prophetic of adaptation (i.e. hypertrophy). Finally, the molecular regulation of MPS by exercise and its regulation via 'anabolic' hormones (e.g. IGF-1) has been questioned, leading to discovery of alternative mechanosensing-signalling to MPS.

  8. Extratropical Transitions in Atlantic Canada: Impacts and Adaptive Responses

    NASA Astrophysics Data System (ADS)

    Masson, Athena; Catto, Norm

    2013-04-01

    . Storm surge damage occurred along the north shore of the Bonavista Peninsula. Similar effects, differing only in the size of the affected areas, have resulted from several extratropical transitions which have impacted Atlantic Canada since July 1989. Extratropical transition "Leslie" impacted Newfoundland on 10-11 September 2012. Although the area affected was comparable to "Igor", wind velocities and rainfall totals were less, fortunately limiting damage. Preparation, advance warning to the population, proaction, and response efforts all showed significant improvement, however, indicating that the experience gained from coping with "Igor" had been successfully applied in adaptation to "Leslie". Extratropical transitions pose a significantly different set of challenges for adaptation in comparison to purely tropical hurricanes, and responses and adaptation strategies should be tailored to address these specific events. Calculating the frequency, magnitude and intensity of potential shifts is important for accurate forecasting and public awareness, safety management, preparedness, and adaptation. Available data indicate an increase in extratropical frequency and severity in Atlantic Canada since 1991, but there are difficulties in establishing the extent and nature of transition for previous storm events. A cautionary policy would assume no significant changes in extratropical transition frequency for Atlantic Canada, but would also acknowledge that large events remain probable.

  9. Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure

    PubMed Central

    Zhang, Yingjiao; Chen, Songcan; Hao, Xiuli; Su, Jian-Qiang; Xue, Ximei; Yan, Yu; Zhu, Yong-Guan; Ye, Jun

    2016-01-01

    Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe–S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe–S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress. PMID:27199962

  10. Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure.

    PubMed

    Zhang, Yingjiao; Chen, Songcan; Hao, Xiuli; Su, Jian-Qiang; Xue, Ximei; Yan, Yu; Zhu, Yong-Guan; Ye, Jun

    2016-01-01

    Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe-S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe-S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress.

  11. PSB27: A thylakoid protein enabling Arabidopsis to adapt to changing light intensity.

    PubMed

    Hou, Xin; Fu, Aigen; Garcia, Veder J; Buchanan, Bob B; Luan, Sheng

    2015-02-03

    In earlier studies we have identified FKBP20-2 and CYP38 as soluble proteins of the chloroplast thylakoid lumen that are required for the formation of photosystem II supercomplexes (PSII SCs). Subsequent work has identified another potential candidate functional in SC formation (PSB27). We have followed up on this possibility and isolated mutants defective in the PSB27 gene. In addition to lack of PSII SCs, mutant plants were severely stunted when cultivated with light of variable intensity. The stunted growth was associated with lower PSII efficiency and defective starch accumulation. In response to high light exposure, the mutant plants also displayed enhanced ROS production, leading to decreased biosynthesis of anthocyanin. Unexpectedly, we detected a second defect in the mutant, namely in CP26, an antenna protein known to be required for the formation of PSII SCs that has been linked to state transitions. Lack of PSII SCs was found to be independent of PSB27, but was due to a mutation in the previously described cp26 gene that we found had no effect on light adaptation. The present results suggest that PSII SCs, despite being required for state transitions, are not associated with acclimation to changing light intensity. Our results are consistent with the conclusion that PSB27 plays an essential role in enabling plants to adapt to fluctuating light intensity through a mechanism distinct from photosystem II supercomplexes and state transitions.

  12. Protein restriction does not impair adaptations induced in cardiomyocytes by exercise in rats.

    PubMed

    Cabral, C A C; Natali, A J; Natali, A Y; Novaes, R D; Lavorato, V N; Drumond, L R; Carneiro Júnior, M A; Silva, M F; Quintão-Junior, J F; Gontijo, L N; Silva, C H O; Felix, L B; Silva, M E

    2013-11-01

    The effect of a treadmill running program on physical performance and morphofunctional adaptations was investigated in control and malnourished rats. Male 4-week old Wistar rats were randomized in groups of 12 animals: control trained (CT), control sedentary (CS), malnourished trained (MT) and malnourished sedentary (MS). Control and malnourished animals received chow with 12% protein or 6% protein, respectively. Trained groups were subjected to a treadmill running program for 8 weeks. Physical performance, biochemical parameters, cardiomyocytes morphology and biomechanics were determined. Malnourished animals presented reduction in body mass, serum levels of total protein, albumin and hemoglobin compared to the control groups. At 1 and 3 Hz cardiomyocytes from CT and MT showed higher cell shortening, speed of contraction and relaxation compared to the other groups. At 3 Hz cardiomyocytes from MS showed reduction in cell shortening and speed of contraction compared to CS. Protein restriction does not prevent the improvement in physical performance or cardiomyocytes biomechanical efficiency and growth in response to exercise. These findings could represent a modulatory effect of exercise to maintain cardiomyocyte growth at the expense of reducing the rate of body growth in order to ensure proper cellular function in conditions of cardiovascular overload imposed by exercise.

  13. Novel protein-protein interaction family proteins involved in chloroplast movement response.

    PubMed

    Kodama, Yutaka; Suetsugu, Noriyuki; Wada, Masamitsu

    2011-04-01

    To optimize photosynthetic activity, chloroplasts change their intracellular location in response to ambient light conditions; chloroplasts move toward low intensity light to maximize light capture, and away from high intensity light to avoid photodamage. Although several proteins have been reported to be involved in the chloroplast photorelocation movement response, any physical interaction among them was not found so far. We recently found a physical interaction between two plant-specific coiled-coil proteins, WEB1 (Weak Chloroplast Movement under Blue Light 1) and PMI2 (Plastid Movement Impaired 2), that were identified to regulate chloroplast movement velocity. Since the both coiled-coil regions of WEB1 and PMI2 were classified into an uncharacterized protein family having DUF827 (DUF: Domain of Unknown Function) domain, it was the first report that DUF827 proteins could mediate protein-protein interaction. In this mini-review article, we discuss regarding molecular function of WEB1 and PMI2, and also define a novel protein family composed of WEB1, PMI2 and WEB1/PMI2-like proteins for protein-protein interaction in land plants.

  14. Adaptation or Malignant Transformation: The Two Faces of Epigenetically Mediated Response to Stress

    PubMed Central

    Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation—the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments. PMID:24187667

  15. Adaptation or malignant transformation: the two faces of epigenetically mediated response to stress.

    PubMed

    Vojta, Aleksandar; Zoldoš, Vlatka

    2013-01-01

    Adaptive response to stress is a fundamental property of living systems. At the cellular level, many different types of stress elicit an essentially limited repertoire of adaptive responses. Epigenetic changes are the main mechanism for medium- to long-term adaptation to accumulated (intense, long-term, or repeated) stress. We propose the adaptive deregulation of the epigenome in response to stress (ADERS) hypothesis which assumes that the unspecific adaptive stress response grows stronger with the increasing stress level, epigenetically activating response gene clusters while progressively deregulating other cellular processes. The balance between the unspecific adaptive response and the general epigenetic deregulation is critical because a strong response can lead to pathology, particularly to malignant transformation. The main idea of our hypothesis is the continuum traversed by a cell subjected to accumulated stress, which lies between an unspecific adaptive response and pathological deregulation--the two extremes sharing the same underlying cause, which is a manifestation of a unified epigenetically mediated adaptive response to stress. The evolutionary potential of epigenetic regulation in multigenerational adaptation is speculatively discussed in the light of neo-Lamarckism. Finally, an approach to testing the proposed hypothesis is presented, relying on either the publicly available datasets or on conducting new experiments.

  16. Physiological responses to food deprivation in the house sparrow, a species not adapted to prolonged fasting.

    PubMed

    Khalilieh, Anton; McCue, Marshall D; Pinshow, Berry

    2012-09-01

    Many wild birds fast during reproduction, molting, migration, or because of limited food availability. Species that are adapted to fasting sequentially oxidize endogenous fuels in three discrete phases. We hypothesized that species not adapted to long fasts have truncated, but otherwise similar, phases of fasting, sequential changes in fuel oxidization, and similar changes in blood metabolites to fasting-adapted species. We tested salient predictions in house sparrows (Passer domesticus biblicus), a subspecies that is unable to tolerate more than ~32 h of fasting. Our main hypothesis was that fasting sparrows sequentially oxidize substrates in the order carbohydrates, lipids, and protein. We dosed 24 house sparrows with [(13)C]glucose, palmitic acid, or glycine and measured (13)CO(2) in their breath while they fasted for 24 h. To ascertain whether blood metabolite levels reflect fasting-induced changes in metabolic fuels, we also measured glucose, triacylglycerides, and β-hydroxybutyrate in the birds' blood. The results of both breath (13)CO(2) and plasma metabolite analyses did not support our hypothesis; i.e., that sparrows have the same metabolic responses characteristic of fasting-adapted species, but on a shorter time scale. Contrary to our main prediction, we found that recently assimilated (13)C-tracers were oxidized continuously in different patterns with no definite peaks corresponding to the three phases of fasting and also that changes in plasma metabolite levels accurately tracked the changes found by breath analysis. Notably, the rate of recently assimilated [(13)C]glycine oxidization was significantly higher (P < 0.001) than that of the other metabolic tracers at all postdosing intervals. We conclude that the inability of house sparrows to fast for longer than 32 h is likely related to their inability to accrue large lipid stores, separately oxidize different fuels, and/or spare protein during fasting.

  17. Plastic and Evolutionary Gene Expression Responses Are Correlated in European Grayling (Thymallus thymallus) Subpopulations Adapted to Different Thermal Environments.

    PubMed

    Mäkinen, Hannu; Papakostas, Spiros; Vøllestad, Leif Asbjørn; Leder, Erica H; Primmer, Craig R

    2016-01-01

    Understanding how populations adapt to changing environmental conditions is a long-standing theme in evolutionary biology. Gene expression changes have been recognized as an important driver of local adaptation, but relatively little is known regarding the direction of change and in particular, about the interplay between plastic and evolutionary gene expression. We have previously shown that the gene expression profiles of European grayling (Thymallus thymallus) populations inhabiting different thermal environments include both plastic and evolutionary components. However, whether the plastic and evolutionary responses were in the same direction was not investigated in detail, nor was the identity of the specific genes involved. In this study, we show that the plastic changes in protein expression in response to different temperatures are highly correlated with the evolutionary response in grayling subpopulations adapted to different thermal environments. This finding provides preliminary evidence that the plastic response most likely facilitates adaptation during the early phases of colonization of thermal environments. The proteins that showed significant changes in expression level between warm and cold temperature treatments were mostly related to muscle development, which is consistent with earlier findings demonstrating muscle mass differentiation between cold and warm grayling populations.

  18. Distributed adaptive diagnosis of sensor faults using structural response data

    NASA Astrophysics Data System (ADS)

    Dragos, Kosmas; Smarsly, Kay

    2016-10-01

    The reliability and consistency of wireless structural health monitoring (SHM) systems can be compromised by sensor faults, leading to miscalibrations, corrupted data, or even data loss. Several research approaches towards fault diagnosis, referred to as ‘analytical redundancy’, have been proposed that analyze the correlations between different sensor outputs. In wireless SHM, most analytical redundancy approaches require centralized data storage on a server for data analysis, while other approaches exploit the on-board computing capabilities of wireless sensor nodes, analyzing the raw sensor data directly on board. However, using raw sensor data poses an operational constraint due to the limited power resources of wireless sensor nodes. In this paper, a new distributed autonomous approach towards sensor fault diagnosis based on processed structural response data is presented. The inherent correlations among Fourier amplitudes of acceleration response data, at peaks corresponding to the eigenfrequencies of the structure, are used for diagnosis of abnormal sensor outputs at a given structural condition. Representing an entirely data-driven analytical redundancy approach that does not require any a priori knowledge of the monitored structure or of the SHM system, artificial neural networks (ANN) are embedded into the sensor nodes enabling cooperative fault diagnosis in a fully decentralized manner. The distributed analytical redundancy approach is implemented into a wireless SHM system and validated in laboratory experiments, demonstrating the ability of wireless sensor nodes to self-diagnose sensor faults accurately and efficiently with minimal data traffic. Besides enabling distributed autonomous fault diagnosis, the embedded ANNs are able to adapt to the actual condition of the structure, thus ensuring accurate and efficient fault diagnosis even in case of structural changes.

  19. REM Sleep Rebound as an Adaptive Response to Stressful Situations

    PubMed Central

    Suchecki, Deborah; Tiba, Paula Ayako; Machado, Ricardo Borges

    2011-01-01

    Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral, and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a way to cope with the adverse stimuli. Chronic, as opposed to acute, stress impairs sleep and has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, conferring even more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the rapid eye movement phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior. PMID:22485105

  20. Cardiac adaptations of bullfrog tadpoles in response to chytrid infection.

    PubMed

    Salla, Raquel Fernanda; Gamero, Fernando Urban; Ribeiro, Larissa Rodrigues; Rizzi, Gisele Miglioranza; Medico, Samuel Espinosa Dal; Rissoli, Rafael Zanelli; Vieira, Conrado Augusto; Silva-Zacarin, Elaine Cristina Mathias; Leite, Domingos Silva; Abdalla, Fábio Camargo; Toledo, Luis Felipe; Costa, Monica Jones

    2015-08-01

    The chytrid fungus Batrachochytrium dendrobatidis (Bd) can result in heart failure in Bd-susceptible species. Since Bd infection generally does not cause mortality in North American bullfrogs, the aim of this work was to verify whether this species presents any cardiac adaptation that could improve the tolerance to the fungus. Thus, we analyzed tadpoles' activity level, relative ventricular mass, ventricle morphology, in loco heart frequency, and in vitro cardiac function. The results indicate that infected animals present an increase in both ventricular relative mass and in myofibrils' incidence, which accompanied the increase in myocytes' diameter. Such morphological alterations enabled an increase in the in vitro twitch force that, in vivo, would result in elevation of the cardiac stroke volume. This response requires much less energy expenditure than an elevation in heart frequency, but still enables the heart to pump a higher volume of blood per minute (i.e., an increase in cardiac output). As a consequence, the energy saved in the regulation of the cardiac function of Bd-infected tadpoles can be employed in other homeostatic adjustments to avoid the lethal effect of the fungus. Whether other species present this ability, and to what extent, remains uncertain, but such possible interspecific variability might explain different mortality rates among different species of Bd-infected amphibians.

  1. Epigenetic memory for stress response and adaptation in plants.

    PubMed

    Kinoshita, Tetsu; Seki, Motoaki

    2014-11-01

    In contrast to the majority of animal species, plants are sessile organisms and are, therefore, constantly challenged by environmental perturbations. Over the past few decades, our knowledge of how plants perceive environmental stimuli has increased considerably, e.g. the mechanisms for transducing environmental stress stimuli into cellular signaling cascades and gene transcription networks. In addition, it has recently been shown that plants can remember past environmental events and can use these memories to aid responses when these events recur. In this mini review, we focus on recent progress in determination of the epigenetic mechanisms used by plants under various environmental stresses. Epigenetic mechanisms are now known to play a vital role in the control of gene expression through small RNAs, histone modifications and DNA methylation. These are inherited through mitotic cell divisions and, in some cases, can be transmitted to the next generation. They therefore offer a possible mechanism for stress memories in plants. Recent studies have yielded evidence indicating that epigenetic mechanisms are indeed essential for stress memories and adaptation in plants.

  2. Distributed reinforcement learning for adaptive and robust network intrusion response

    NASA Astrophysics Data System (ADS)

    Malialis, Kleanthis; Devlin, Sam; Kudenko, Daniel

    2015-07-01

    Distributed denial of service (DDoS) attacks constitute a rapidly evolving threat in the current Internet. Multiagent Router Throttling is a novel approach to defend against DDoS attacks where multiple reinforcement learning agents are installed on a set of routers and learn to rate-limit or throttle traffic towards a victim server. The focus of this paper is on online learning and scalability. We propose an approach that incorporates task decomposition, team rewards and a form of reward shaping called difference rewards. One of the novel characteristics of the proposed system is that it provides a decentralised coordinated response to the DDoS problem, thus being resilient to DDoS attacks themselves. The proposed system learns remarkably fast, thus being suitable for online learning. Furthermore, its scalability is successfully demonstrated in experiments involving 1000 learning agents. We compare our approach against a baseline and a popular state-of-the-art throttling technique from the network security literature and show that the proposed approach is more effective, adaptive to sophisticated attack rate dynamics and robust to agent failures.

  3. Architectural adaptation and protein expression patterns of Salmonella enterica serovar Enteritidis biofilms under laminar flow conditions.

    PubMed

    Mangalappalli-Illathu, Anil K; Lawrence, John R; Swerhone, George D W; Korber, Darren R

    2008-03-31

    Salmonella enterica serovar Enteritidis is a significant biofilm-forming pathogen. The influence of a 10-fold difference in nutrient laminar flow velocity on the dynamics of Salmonella Enteritidis biofilm formation and protein expression profiles were compared in order to ascertain how flow velocity influenced biofilm structure and function. Low-flow (0.007 cm s(-1)) biofilms consisted of diffusely-arranged microcolonies which grew until merging by approximately 72 h. High-flow (0.07 cm s(-1)) biofilms were significantly thicker (36+/-3 microm (arithmetic mean+/-standard error; n=225) versus 16+/-2 microm for low-flow biofilms at 120 h) and consisted of large bacterial mounds interspersed by water channels. Lectin-binding analysis of biofilm exopolymers revealed a significantly higher (P<0.05) proportion of N-acetylgalactosamine (GalNAc) in low-flow biofilms (55.2%), relative to only 1.2% in high-flow biofilms. Alternatively, the proportions of alpha-L-fucose and N-acetylglucosamine (GlcNAc2)-N-acetylneuraminic acid (NeuNAc) polymer-conjugates were significantly higher (P<0.05) in high-flow biofilms (69.1% and 29.6%, respectively) than low-flow biofilms (33.1% and 11.7%, respectively). Despite an apparent flow rate-based physiologic effect on biofilm structure and exopolymer composition, no major shift in whole-cell protein expression patterns was seen between 168 h-old low-flow and high-flow biofilms, and notably did not include any response involving the stress response proteins, DnaK, SodB, and Tpx. Proteins involved in degradation and energy metabolism (PduA, GapA, GpmA, Pgk, and RpiA), RNA and protein biosynthesis (Tsf, TufA, and RpoZ), cell processes (Crr, MalE, and PtsH), and adaptation (GrcA), and some hypothetical proteins (YcbL and YnaF) became up-regulated in both biofilm systems relative to a 168 h-old planktonic cell control. Our results indicate that Salmonella Enteritidis biofilms altered their structure and extracellular glycoconjugate composition

  4. Insights into yeast adaptive response to the agricultural fungicide mancozeb: a toxicoproteomics approach.

    PubMed

    Santos, Pedro M; Simões, Tânia; Sá-Correia, Isabel

    2009-02-01

    Toxicogenomics has the potential to elucidate gene-environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signalling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analysed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70-family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. Our results also suggest that this study provided powerful indications that may be useful to expand the knowledge obtained in yeast not only to the global response to mancozeb toxicity in phytopathogenic fungi but also to humans.

  5. Defective Expression of the Mitochondrial-tRNA Modifying Enzyme GTPBP3 Triggers AMPK-Mediated Adaptive Responses Involving Complex I Assembly Factors, Uncoupling Protein 2, and the Mitochondrial Pyruvate Carrier

    PubMed Central

    Esteve, Juan M.; Villarroya, Magda; Aguado, Carmen; Enríquez, J. Antonio; Knecht, Erwin; Armengod, M.-Eugenia

    2015-01-01

    GTPBP3 is an evolutionary conserved protein presumably involved in mitochondrial tRNA (mt-tRNA) modification. In humans, GTPBP3 mutations cause hypertrophic cardiomyopathy with lactic acidosis, and have been associated with a defect in mitochondrial translation, yet the pathomechanism remains unclear. Here we use a GTPBP3 stable-silencing model (shGTPBP3 cells) for a further characterization of the phenotype conferred by the GTPBP3 defect. We experimentally show for the first time that GTPBP3 depletion is associated with an mt-tRNA hypomodification status, as mt-tRNAs from shGTPBP3 cells were more sensitive to digestion by angiogenin than tRNAs from control cells. Despite the effect of stable silencing of GTPBP3 on global mitochondrial translation being rather mild, the steady-state levels and activity of Complex I, and cellular ATP levels were 50% of those found in the controls. Notably, the ATPase activity of Complex V increased by about 40% in GTPBP3 depleted cells suggesting that mitochondria consume ATP to maintain the membrane potential. Moreover, shGTPBP3 cells exhibited enhanced antioxidant capacity and a nearly 2-fold increase in the uncoupling protein UCP2 levels. Our data indicate that stable silencing of GTPBP3 triggers an AMPK-dependent retrograde signaling pathway that down-regulates the expression of the NDUFAF3 and NDUFAF4 Complex I assembly factors and the mitochondrial pyruvate carrier (MPC), while up-regulating the expression of UCP2. We also found that genes involved in glycolysis and oxidation of fatty acids are up-regulated. These data are compatible with a model in which high UCP2 levels, together with a reduction in pyruvate transport due to the down-regulation of MPC, promote a shift from pyruvate to fatty acid oxidation, and to an uncoupling of glycolysis and oxidative phosphorylation. These metabolic alterations, and the low ATP levels, may negatively affect heart function. PMID:26642043

  6. Effectively explore metastable states of proteins by adaptive nonequilibrium driving simulations

    NASA Astrophysics Data System (ADS)

    Wan, Biao; Xu, Shun; Zhou, Xin

    2017-03-01

    Nonequilibrium drivings applied in molecular dynamics (MD) simulations can efficiently extend the visiting range of protein conformations, but might compel systems to go far away from equilibrium and thus mainly explore irrelevant conformations. Here we propose a general method, called adaptive nonequilibrium simulation (ANES), to automatically adjust the external driving on the fly, based on the feedback of the short-time average response of system. Thus, the ANES approximately keeps the local equilibrium but efficiently accelerates the global motion. We illustrate the capability of the ANES in highly efficiently exploring metastable conformations in the deca-alanine peptide and find that the 0.2 -μ s ANES approximately captures the important states and folding and unfolding pathways in the HP35 solution by comparing with the result of the recent 398 -μ s equilibrium MD simulation on Anton [S. Piana et al., Proc. Natl. Acad. Sci. USA 109, 17845 (2012), 10.1073/pnas.1201811109].

  7. The Unfolded Protein Response and Gastrointestinal Disease

    PubMed Central

    Kaser, Arthur; Adolph, Timon Erik; Blumberg, Richard S

    2013-01-01

    As the inner lining of the gastrointestinal tract, the intestinal epithelium serves an essential role in innate immune function at the interface between the host and microbiota. Given the unique environmental challenges and thus physiologic secretory functions of this surface, it is exquisitely sensitive to perturbations that affect its capacity to resolve endoplasmic reticulum (ER) stress. Genetic deletion of factors involved in the unfolded protein response (UPR), which functions in the resolution of ER stress that arises from misfolded proteins, result in spontaneous intestinal inflammation closely mimicking human inflammatory bowel disease (IBD). This is demonstrated by observations wherein deletion of genes such as Xbp1 and Agr2 profoundly affects the intestinal epithelium and results in spontaneous intestinal inflammation. Moreover, both genes, along with others (e.g. ORDML3) represent genetic risk factors for human IBD, both Crohn’s disease and ulcerative colitis. Here we review the current mechanistic understanding for how unresolved ER stress can lead to intestinal inflammation, and highlight the findings that implicate ER stress as a genetically affected biological pathway in IBD. We further discuss environmental and microbial factors that might impact on the epithelium’s capacity to resolve ER stress, and which may constitute exogenous factors that may precipitate disease in genetically susceptible individuals. PMID:23588234

  8. Durable antitumor responses to CD47 blockade require adaptive immune stimulation

    PubMed Central

    Sockolosky, Jonathan T.; Dougan, Michael; Ingram, Jessica R.; Ho, Chia Chi M.; Kauke, Monique J.; Almo, Steven C.; Ploegh, Hidde L.; Garcia, K. Christopher

    2016-01-01

    Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). Interference with the CD47–SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy. PMID:27091975

  9. Transcriptomic Analysis of Laribacter hongkongensis Reveals Adaptive Response Coupled with Temperature

    PubMed Central

    Kong, Hoi-Kuan; Law, Hon-Wai; Liu, Xuan; Law, Carmen O. K.; Pan, Qing; Gao, Lin; Xiong, Lifeng; Lau, Susanna K. P.; Woo, Patrick C. Y.; Lau, Terrence chi kong

    2017-01-01

    Bacterial adaptation to different hosts requires transcriptomic alteration in response to the environmental conditions. Laribacter hongkongensis is a gram-negative, facultative anaerobic, urease-positive bacillus caused infections in liver cirrhosis patients and community-acquired gastroenteritis. It was also found in intestine from commonly consumed freshwater fishes and drinking water reservoirs. Since L. hongkongensis could survive as either fish or human pathogens, their survival mechanisms in two different habitats should be temperature-regulated and highly complex. Therefore, we performed transcriptomic analysis of L. hongkongensis at body temperatures of fish and human in order to elucidate the versatile adaptation mechanisms coupled with the temperatures. We identified numerous novel temperature-induced pathways involved in host pathogenesis, in addition to the shift of metabolic equilibriums and overexpression of stress-related proteins. Moreover, these pathways form a network that can be activated at a particular temperature, and change the physiology of the bacteria to adapt to the environments. In summary, the dynamic of transcriptomes in L. hongkongensis provides versatile strategies for the bacterial survival at different habitats and this alteration prepares the bacterium for the challenge of host immunity. PMID:28085929

  10. Durable antitumor responses to CD47 blockade require adaptive immune stimulation.

    PubMed

    Sockolosky, Jonathan T; Dougan, Michael; Ingram, Jessica R; Ho, Chia Chi M; Kauke, Monique J; Almo, Steven C; Ploegh, Hidde L; Garcia, K Christopher

    2016-05-10

    Therapeutic antitumor antibodies treat cancer by mobilizing both innate and adaptive immunity. CD47 is an antiphagocytic ligand exploited by tumor cells to blunt antibody effector functions by transmitting an inhibitory signal through its receptor signal regulatory protein alpha (SIRPα). Interference with the CD47-SIRPα interaction synergizes with tumor-specific monoclonal antibodies to eliminate human tumor xenografts by enhancing macrophage-mediated antibody-dependent cellular phagocytosis (ADCP), but synergy between CD47 blockade and ADCP has yet to be demonstrated in immunocompetent hosts. Here, we show that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice. Durable tumor immunity required programmed death-ligand 1 (PD-L1) blockade in combination with an antitumor antibody, with incorporation of CD47 antagonism substantially improving response rates. Our results highlight an underappreciated contribution of the adaptive immune system to anti-CD47 adjuvant therapy and suggest that targeting both innate and adaptive immune checkpoints can potentiate the vaccinal effect of antitumor antibody therapy.

  11. Evolutionary responses of innate Immunity to adaptive immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Innate immunity is present in all metazoans, whereas the evolutionarily more novel adaptive immunity is limited to jawed fishes and their descendants (gnathostomes). We observe that the organisms that possess adaptive immunity lack diversity in their innate pattern recognition receptors (PRRs), rais...

  12. Human adaptation genetic response suites: Toward new interventions and countermeasures for spaceflight

    NASA Astrophysics Data System (ADS)

    Sundaresan, A.; Pellis, N. R.

    2005-08-01

    Genetic response suites in human lymphocytes in response to microgravity are important to identify and further study in order to augment human physiological adaptation to novel environments. Emerging technologies, such as DNA micro array profiling, have the potential to identify novel genes that are involved in mediating adaptation to these environments. These genes may prove to be therapeutically valuable as new targets for countermeasures, or as predictive biomarkers of response to these new environments. Human lymphocytes cultured in 1g and microgravity analog culture were analyzed for their differential gene expression response. Different groups of genes related to the immune response, cardiovascular system and stress response were then analyzed. Analysis of cells from multiple donors reveals a small shared set that are likely to be essential to adaptation. These three groups focus on human adaptation to new environments. The shared set contains genes related to T cell activation, immune response and stress response to analog microgravity.

  13. Human Adaptation Genetic Response Suites: Toward New Interventions and Countermeasures for Spaceflight

    NASA Technical Reports Server (NTRS)

    Sundaresan, A.; Pellis, N. R.

    2005-01-01

    Genetic response suites in human lymphocytes in response to microgravity are important to identify and further study in order to augment human physiological adaptation to novel environments. Emerging technologies, such as DNA micro array profiling, have the potential to identify novel genes that are involved in mediating adaptation to these environments. These genes may prove to be therapeutically valuable as new targets for countermeasures, or as predictive biomarkers of response to these new environments. Human lymphocytes cultured in lg and microgravity analog culture were analyzed for their differential gene expression response. Different groups of genes related to the immune response, cardiovascular system and stress response were then analyzed. Analysis of cells from multiple donors reveals a small shared set that are likely to be essential to adaptation. These three groups focus on human adaptation to new environments. The shared set contains genes related to T cell activation, immune response and stress response to analog microgravity.

  14. The acid adaptive tolerance response in Campylobacter jejuni induces a global response, as suggested by proteomics and microarrays

    PubMed Central

    Varsaki, Athanasia; Murphy, Caroline; Barczynska, Alicja; Jordan, Kieran; Carroll, Cyril

    2015-01-01

    Campylobacter jejuni CI 120 is a natural isolate obtained during poultry processing and has the ability to induce an acid tolerance response (ATR) to acid + aerobic conditions in early stationary phase. Other strains tested they did not induce an ATR or they induced it in exponential phase. Campylobacter spp. do not contain the genes that encode the global stationary phase stress response mechanism. Therefore, the aim of this study was to identify genes that are involved in the C. jejuni CI 120 early stationary phase ATR, as it seems to be expressing a novel mechanism of stress tolerance. Two-dimensional gel electrophoresis was used to examine the expression profile of cytosolic proteins during the C. jejuni CI 120 adaptation to acid + aerobic stress and microarrays to determine the genes that participate in the ATR. The results indicate induction of a global response that activated a number of stress responses, including several genes encoding surface components and genes involved with iron uptake. The findings of this study provide new insights into stress tolerance of C. jejuni, contribute to a better knowledge of the physiology of this bacterium and highlight the diversity among different strains. PMID:26221965

  15. The acid adaptive tolerance response in Campylobacter jejuni induces a global response, as suggested by proteomics and microarrays.

    PubMed

    Varsaki, Athanasia; Murphy, Caroline; Barczynska, Alicja; Jordan, Kieran; Carroll, Cyril

    2015-11-01

    Campylobacter jejuni CI 120 is a natural isolate obtained during poultry processing and has the ability to induce an acid tolerance response (ATR) to acid + aerobic conditions in early stationary phase. Other strains tested they did not induce an ATR or they induced it in exponential phase. Campylobacter spp. do not contain the genes that encode the global stationary phase stress response mechanism. Therefore, the aim of this study was to identify genes that are involved in the C. jejuni CI 120 early stationary phase ATR, as it seems to be expressing a novel mechanism of stress tolerance. Two-dimensional gel electrophoresis was used to examine the expression profile of cytosolic proteins during the C. jejuni CI 120 adaptation to acid + aerobic stress and microarrays to determine the genes that participate in the ATR. The results indicate induction of a global response that activated a number of stress responses, including several genes encoding surface components and genes involved with iron uptake. The findings of this study provide new insights into stress tolerance of C. jejuni, contribute to a better knowledge of the physiology of this bacterium and highlight the diversity among different strains.

  16. Plant Organellar Proteomics in Response to Dehydration: Turning Protein Repertoire into Insights

    PubMed Central

    Gupta, Deepti B.; Rai, Yogita; Gayali, Saurabh; Chakraborty, Subhra; Chakraborty, Niranjan

    2016-01-01

    Stress adaptation or tolerance in plants is a complex phenomenon involving changes in physiological and metabolic processes. Plants must develop elaborate networks of defense mechanisms, and adapt to and survive for sustainable agriculture. Water-deficit or dehydration is the most critical environmental factor that plants are exposed to during their life cycle, which influences geographical distribution and productivity of many crop species. The cellular responses to dehydration are orchestrated by a series of multidirectional relays of biochemical events at organelle level. The new challenge is to dissect the underlying mechanisms controlling the perception of stress signals and their transmission to cellular machinery for activation of adaptive responses. The completeness of current descriptions of spatial distribution of proteins, the relevance of subcellular locations in diverse functional processes, and the changes of protein abundance in response to dehydration hold the key to understanding how plants cope with such stress conditions. During past decades, organellar proteomics has proved to be useful not only for deciphering reprograming of plant responses to dehydration, but also to dissect stress–responsive pathways. This review summarizes a range of organellar proteomics investigations under dehydration to gain a holistic view of plant responses to water-deficit conditions, which may facilitate future efforts to develop genetically engineered crops for better adaptation. PMID:27148291

  17. Glycaemic Response to Quality Protein Maize Grits

    PubMed Central

    Panlasigui, Leonora N.; Bayaga, Cecile L. T.; Barrios, Erniel B.; Cochon, Kim L.

    2010-01-01

    Background. Carbohydrates have varied rates of digestion and absorption that induces different hormonal and metabolic responses in the body. Given the abundance of carbohydrate sources in the Philippines, the determination of the glycaemic index (GI) of local foods may prove beneficial in promoting health and decreasing the risk of diabetes in the country. Methods. The GI of Quality Protein Maize (QPM) grits, milled rice, and the mixture of these two food items were determined in ten female subjects. Using a randomized crossover design, the control bread and three test foods were given on separate occasions after an overnight fast. Blood samples were collected through finger prick at time intervals of 0, 15, 30, 45, 60, 90, and 120 min and analyzed for glucose concentrations. Results. The computed incremental area under the glucose response curve (IAUC) varies significantly across test foods (P < .0379) with the pure QPM grits yielding the lowest IAUC relative to the control by 46.38. Resulting GI values of the test foods (bootstrapped) were 80.36 (SEM 14.24), 119.78 (SEM 18.81), and 93.17 (SEM 27.27) for pure QPM grits, milled rice, and rice-QPM grits mixture, respectively. Conclusion. Pure QPM corn grits has a lower glycaemic response compared to milled rice and the rice-corn grits mixture, which may be related in part to differences in their dietary fibre composition and physicochemical characteristics. Pure QPM corn grits may be a more health beneficial food for diabetic and hyperlipidemic individuals. PMID:20862364

  18. Specific adaptation of gastric emptying to diets with differing protein content in the rat: is endogenous cholecystokinin implicated?

    PubMed Central

    Shi, G; Leray, V; Scarpignato, C; Bentouimou, N; Varannes, S; Cherbut, C; Galmiche, J

    1997-01-01

    peptone meal strongly and significantly (p<0.05) increased plasma CCK levels in rats fed a medium protein (regular) diet. Results were similar in rats receiving a low protein diet (p<0.05) but not in rats on a high protein diet (p>0.05). As a consequence, postprandial plasma levels of CCK in rats fed with a medium or low protein diet were significantly (p<0.05) higher than those in rats receiving a high protein diet. In rats on high and low protein diets, dose response curves to CCK-8 were virtually identical, suggesting that dietary protein intake has no influence on the effect of exogenous CCK.
Conclusions—These results clearly show that gastric emptying of a protein containing meal can be modified by previous dietary protein intake. This effect, which is time dependent and meal specific, may be related to changes in endogenous CCK release which will affect emptying rate. While the exact mechanisms underlying this adaptive response need to be studied and clarified further, these results emphasise the importance of dietary history in the evaluation and interpretation of gastric emptying data. 

 Keywords: diet; protein content; gastric emptying; cholecystokinin PMID:9414966

  19. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response.

    PubMed

    Beaumont, Martin; Andriamihaja, Mireille; Lan, Annaïg; Khodorova, Nadezda; Audebert, Marc; Blouin, Jean-Marc; Grauso, Marta; Lancha, Luciana; Benetti, Pierre-Henri; Benamouzig, Robert; Tomé, Daniel; Bouillaud, Frédéric; Davila, Anne-Marie; Blachier, François

    2016-04-01

    Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1α (Hif-1α) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the γH2AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite.

  20. Adaptive response of bacteria: Multiple hurdles, cross-tolerance and tools to illustrate underlying mechanisms

    NASA Astrophysics Data System (ADS)

    Paramythiotis, Spyridon; Skandamis, Panagiotis N.

    2015-01-01

    A basic principle in the bacterial resistance against lethal stresses is that exposure of microbial cells to a sublethal hurdle (e.g., pH 5.0, 3% NaCl, or 48°C) may induce resistance to lethal level of the same or different stress. The latter is called "cross-tolerance" and the bacteria experiencing such situations are termed "stress-hardened". The majority of scientific reports on the adaptive responses of bacteria to stresses have recently addressed the need to elucidate the underlying mechanisms controlling bacterial stress response. This in turn, will assist in the efficient application of the multiple hurdle approach, e.g., by selecting specific sanitizers, combining stress treatments or antimicrobials, especially in mild processing, against specific cellular targets, eliminating the possibility of the development of stress adapted cells. Common scientific approaches for studying the link between phenotype (e.g., inactivation, survival, or growth) and physiology is the assessment of global transcriptional changes (up- or down-regulation) or those of certain genes, as well as of proteins involved in certain metabolic pathways, occurring during exposure to stress. This may also be performed in parallel to comparative evaluation of the phenotypic response of wild and mutant strains. The post-genomics research on foodborne pathogens has extended our knowledge beyond their phenotypic behavior and may offer mechanistic insights in the following: (i) the top-down approach (induction), which is the search of the underlying mechanisms (low level) responsible for a specific phenotype based on "-omic" studies; and (ii) the bottom-up approach (deduction), which starts from intracellular level and forms a mechanistic (functional) basis for the cellular response. All these may eventually enable the development of mechanistic microbial models and efficient strategies for controlling survival and growth of pathogens in foods.

  1. The "adaptive responses" of low concentrations of HBCD in L02 cells and the underlying molecular mechanisms.

    PubMed

    An, Jing; Guo, Panpan; Shang, Yu; Zhong, Yufang; Zhang, Xinyu; Yu, Yingxin; Yu, Zhiqiang

    2016-02-01

    This study aimed to investigate the "adaptive responses" of hexabromocyclododecanes (HBCD) at environmentally relevant concentrations in human hepatocytes L02. L02 cells were pre-treated with low concentrations of HBCD (10(-13)-10(-11) M), followed by treatment with high concentrations of HBCD, α-hexachlorocyclohexane (α-HCH), polychlorinated biphenyls (PCBs), or polybrominated diphenyl ether-47 (BDE47). The results showed that the pre-treatment with low concentrations of HBCD induced "adaptive responses" to high concentrations of HBCD/α-HCH exposure (but not to PCBs and BDE47), as evidenced by attenuation of survival inhibition, reactive oxygen species (ROS) over-production, and deoxyribonucleic acid (DNA) damage induction. The "adaptive responses" induced by low concentrations of HBCD, which depended on the activation of the phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, reduced the phosphorylation of adenosine monophosphate-activated kinase (AMPK) and enhanced the phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK). The observations were further confirmed by the experiments with inhibitors. Moreover, the evaluation on the changes of metabolic enzymes revealed that HBCD and α-HCH shared a similar pattern of cytochrome P450 induction (CYP2B6), which was different from those of PCBs and BDE47 (CYP1A1 and CYP2B6). These results indicated that low concentrations of HBCD could induce "adaptive responses" to the subsequent treatment with high concentrations of HBCD/α-HCH in L02 cells, which was associated with the PI3K/Akt pathway, and AMPK and p38 MAPK signaling. The "adaptive responses" seemed to be dependent on the types of chemicals in terms of the metabolic patterns and chemical structures.

  2. The MRL proteins: adapting cell adhesion, migration and growth.

    PubMed

    Coló, Georgina P; Lafuente, Esther M; Teixidó, Joaquin

    2012-01-01

    MIG-10, RIAM and Lamellipodin (Lpd) are the founding members of the MRL family of multi-adaptor molecules. These proteins have common domain structures but display distinct functions in cell migration and adhesion, signaling, and in cell growth. The binding of RIAM with active Rap1 and with talin provides these MRL molecules with important regulatory roles on integrin-mediated cell adhesion and migration. Furthermore, RIAM and Lpd can regulate actin dynamics through their binding to actin regulatory Ena/VASP proteins. Recent data generated with the Drosophila MRL ortholog called Pico and with RIAM in melanoma cells indicate that these proteins can also regulate cell growth. As MRL proteins represent a relatively new family, many questions on their structure-function relationships remain unanswered, including regulation of their expression, post-translational modifications, new interactions, involvement in signaling and their knockout mice phenotype.

  3. [The possible role of the elements of protein secondary structure in adaptation to the action of ionizing radiation].

    PubMed

    Kharchenko, L I; Pavlovskaia, T E

    1997-01-01

    Changes in the secondary structure of enzymes induced by gamma-rays 60Co at doses not exceeding one ionization per macromolecule were studied to elucidate a possible role of radiation-chemical processes in the evolution of proteins. The data on the comparative radioresistance of various types of secondary protein structures, alpha-helix, parallel and anti-parallel beta-structures, and beta-turn, were obtained by the method of circular dichroism. It was shown that beta-turns were resistant against radiation, alpha-helix was relatively stable, and beta-layer underwent significant changes. The importance of these structural types in the evolution of proteins is discussed. A special role of beta-turn as structural elements fixing the confirmation of macromolecules and therefore responsible for adaptation of the protein structure against a constant radiation background is proposed.

  4. No Evidence for a Low Linear Energy Transfer Adaptive Response in Irradiated RKO Cells

    SciTech Connect

    Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.; Lewis, Adam J.; Morgan, William F.

    2011-01-06

    It has become increasingly evident from reports in the literature that there are many confounding factors that are capable of modulating radiation induced non-targeted responses such as the bystander effect and the adaptive response. In this paper we examine recent data that suggest that the observation of non-targeted responses may not be universally observable for differing radiation qualities. We have conducted a study of the adaptive response following low LET exposures for human colon carcinoma cells and failed to observe adaption for the endpoints of clonogenic survival or micronucleus formation.

  5. Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria infection by reinforcing host iron metabolism.

    PubMed

    Zhao, Hong; Konishi, Aki; Fujita, Yukiko; Yagi, Masanori; Ohata, Keiichi; Aoshi, Taiki; Itagaki, Sawako; Sato, Shintaro; Narita, Hirotaka; Abdelgelil, Noha H; Inoue, Megumi; Culleton, Richard; Kaneko, Osamu; Nakagawa, Atsushi; Horii, Toshihiro; Akira, Shizuo; Ishii, Ken J; Coban, Cevayir

    2012-11-15

    Plasmodium parasites multiply within host erythrocytes, which contain high levels of iron, and parasite egress from these cells results in iron release and host anemia. Although Plasmodium requires host iron for replication, how host iron homeostasis and responses to these fluxes affect Plasmodium infection are incompletely understood. We determined that Lipocalin 2 (Lcn2), a host protein that sequesters iron, is abundantly secreted during human (P. vivax) and mouse (P. yoeliiNL) blood-stage malaria infections and is essential to control P. yoeliiNL parasitemia, anemia, and host survival. During infection, Lcn2 bolsters both host macrophage function and granulocyte recruitment and limits reticulocytosis, or the expansion of immature erythrocytes, which are the preferred target cell of P. yoeliiNL. Additionally, a chronic iron imbalance due to Lcn2 deficiency results in impaired adaptive immune responses against Plasmodium parasites. Thus, Lcn2 exerts antiparasitic effects by maintaining iron homeostasis and promoting innate and adaptive immune responses.

  6. Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3.

    PubMed

    Kramerova, I; Kudryashova, E; Ermolova, N; Saenz, A; Jaka, O; López de Munain, A; Spencer, M J

    2012-07-15

    Mutations in the non-lysosomal, cysteine protease calpain 3 (CAPN3) result in the disease limb girdle muscular dystrophy type 2A (LGMD2A). CAPN3 is localized to several subcellular compartments, including triads, where it plays a structural, rather than a proteolytic, role. In the absence of CAPN3, several triad components are reduced, including the major Ca(2+) release channel, ryanodine receptor (RyR). Furthermore, Ca(2+) release upon excitation is impaired in the absence of CAPN3. In the present study, we show that Ca-calmodulin protein kinase II (CaMKII) signaling is compromised in CAPN3 knockout (C3KO) mice. The CaMK pathway has been previously implicated in promoting the slow skeletal muscle phenotype. As expected, the decrease in CaMKII signaling that was observed in the absence of CAPN3 is associated with a reduction in the slow versus fast muscle fiber phenotype. We show that muscles of WT mice subjected to exercise training activate the CaMKII signaling pathway and increase expression of the slow form of myosin; however, muscles of C3KO mice do not exhibit these adaptive changes to exercise. These data strongly suggest that skeletal muscle's adaptive response to functional demand is compromised in the absence of CAPN3. In agreement with our mouse studies, RyR levels were also decreased in biopsies from LGMD2A patients. Moreover, we observed a preferential pathological involvement of slow fibers in LGMD2A biopsies. Thus, impaired CaMKII signaling and, as a result, a weakened muscle adaptation response identify a novel mechanism that may underlie LGMD2A and suggest a pharmacological target that should be explored for therapy.

  7. Adaptive changes of the yeast mitochondrial proteome in response to salt stress.

    PubMed

    Martínez-Pastor, Mar; Proft, Markus; Pascual-Ahuir, Amparo

    2010-10-01

    Mitochondria are dynamic organelles with the capacity to adapt to environmental stimuli and stress. Here we use yeast (Saccharomyces cerevisiae) in combination with proteomic approaches to quantify the changes in the protein composition of mitochondria in the presence of salt stress provoked by NaCl. We identified 15 proteins that were more than twofold overrepresented in salt adapted mitochondria. These proteins are mainly involved in the oxidative stress defense, the biosynthesis of amino acids and ubiquinone or in the metabolism of pyruvate and acetate. Loss of function of most of the upregulated proteins did not result in a significant growth phenotype under high salt conditions. However, all identified proteins were necessary to sustain efficient growth under oxidative stress caused by hydrogen peroxide. Additionally, a subset of outer mitochondrial membrane proteins was shown to be upregulated upon salt stress. We furthermore identified nine proteins that were more than threefold underrepresented in salt adapted mitochondria. These proteins were mainly glycolytic enzymes or proteins with a predominant localization at the endoplasmatic reticulum. Our results underline the complex nature of the stress adaptation of mitochondria and identify functional groups of proteins whose specific role in salt resistance should be revealed in the future.

  8. The Vibrio cholerae Cpx Envelope Stress Response Senses and Mediates Adaptation to Low Iron

    PubMed Central

    Acosta, Nicole; Pukatzki, Stefan

    2014-01-01

    The Cpx pathway, a two-component system that employs the sensor histidine kinase CpxA and the response regulator CpxR, regulates crucial envelope stress responses across bacterial species and affects antibiotic resistance. To characterize the CpxR regulon in Vibrio cholerae, the transcriptional profile of the pandemic V. cholerae El Tor C6706 strain was examined upon overexpression of cpxR. Our data show that the Cpx regulon of V. cholerae is enriched in genes encoding membrane-localized and transport proteins, including a large number of genes known or predicted to be iron regulated. Activation of the Cpx pathway further led to the expression of TolC, the major outer membrane pore, and of components of two RND efflux systems in V. cholerae. We show that iron chelation, toxic compounds, or deletion of specific RND efflux components leads to Cpx pathway activation. Furthermore, mutations that eliminate the Cpx response or members of its regulon result in growth phenotypes in the presence of these inducers that, together with Cpx pathway activation, are partially suppressed by iron. Cumulatively, our results suggest that a major function of the Cpx response in V. cholerae is to mediate adaptation to envelope perturbations caused by toxic compounds and the depletion of iron. PMID:25368298

  9. Innate and adaptive immune responses in migrating spring-run adult chinook salmon, Oncorhynchus tshawytscha

    USGS Publications Warehouse

    Dolan, Brian P.; Fisher, Kathleen M.; Colvin, Michael E.; Benda, Susan E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

    2016-01-01

    Adult Chinook salmon (Oncorhynchus tshawytscha) migrate from salt water to freshwater streams to spawn. Immune responses in migrating adult salmon are thought to diminish in the run up to spawning, though the exact mechanisms for diminished immune responses remain unknown. Here we examine both adaptive and innate immune responses as well as pathogen burdens in migrating adult Chinook salmon in the Upper Willamette River basin. Messenger RNA transcripts encoding antibody heavy chain molecules slightly diminish as a function of time, but are still present even after fish have successfully spawned. In contrast, the innate anti-bacterial effector proteins present in fish plasma rapidly decrease as spawning approaches. Fish also were examined for the presence and severity of eight different pathogens in different organs. While pathogen burden tended to increase during the migration, no specific pathogen signature was associated with diminished immune responses. Transcript levels of the immunosuppressive cytokines IL-10 and TGF beta were measured and did not change during the migration. These results suggest that loss of immune functions in adult migrating salmon are not due to pathogen infection or cytokine-mediated immune suppression, but is rather part of the life history of Chinook salmon likely induced by diminished energy reserves or hormonal changes which accompany spawning.

  10. A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite

  11. Catalysis of protein folding by chaperones accelerates evolutionary dynamics in adapting cell populations.

    PubMed

    Cetinbaş, Murat; Shakhnovich, Eugene I

    2013-01-01

    Although molecular chaperones are essential components of protein homeostatic machinery, their mechanism of action and impact on adaptation and evolutionary dynamics remain controversial. Here we developed a physics-based ab initio multi-scale model of a living cell for population dynamics simulations to elucidate the effect of chaperones on adaptive evolution. The 6-loci genomes of model cells encode model proteins, whose folding and interactions in cellular milieu can be evaluated exactly from their genome sequences. A genotype-phenotype relationship that is based on a simple yet non-trivially postulated protein-protein interaction (PPI) network determines the cell division rate. Model proteins can exist in native and molten globule states and participate in functional and all possible promiscuous non-functional PPIs. We find that an active chaperone mechanism, whereby chaperones directly catalyze protein folding, has a significant impact on the cellular fitness and the rate of evolutionary dynamics, while passive chaperones, which just maintain misfolded proteins in soluble complexes have a negligible effect on the fitness. We find that by partially releasing the constraint on protein stability, active chaperones promote a deeper exploration of sequence space to strengthen functional PPIs, and diminish the non-functional PPIs. A key experimentally testable prediction emerging from our analysis is that down-regulation of chaperones that catalyze protein folding significantly slows down the adaptation dynamics.

  12. Differential Proteomic Profiles of Pleurotus ostreatus in Response to Lignocellulosic Components Provide Insights into Divergent Adaptive Mechanisms

    PubMed Central

    Xiao, Qiuyun; Ma, Fuying; Li, Yan; Yu, Hongbo; Li, Chengyun; Zhang, Xiaoyu

    2017-01-01

    Pleurotus ostreatus is a white rot fungus that grows on lignocellulosic biomass by metabolizing the main constituents. Extracellular enzymes play a key role in this process. During the hydrolysis of lignocellulose, potentially toxic molecules are released from lignin, and the molecules are derived from hemicellulose or cellulose that trigger various responses in fungus, thereby influencing mycelial growth. In order to characterize the mechanism underlying the response of P. ostreatus to lignin, we conducted a comparative proteomic analysis of P. ostreatus grown on different lignocellulose substrates. In this work, the mycelium proteome of P. ostreatus grown in liquid minimal medium with lignin, xylan, and carboxymethyl cellulose (CMC) was analyzed using the complementary two-dimensional gel electrophoresis (2-DE) approach; 115 proteins were identified, most of which were classified into five types according to their function. Proteins with an antioxidant function that play a role in the stress response were upregulated in response to lignin. Most proteins involving in carbohydrate and energy metabolism were less abundant in lignin. Xylan and CMC may enhanced the process of carbohydrate metabolism by regulating the level of expression of various carbohydrate metabolism-related proteins. The change of protein expression level was related to the adaptability of P. ostreatus to lignocellulose. These findings provide novel insights into the mechanisms underlying the response of white-rot fungus to lignocellulose. PMID:28386251

  13. Novel roles of the unfolded protein response in the control of tumor development and aggressiveness.

    PubMed

    Dejeans, Nicolas; Barroso, Kim; Fernandez-Zapico, Martin E; Samali, Afshin; Chevet, Eric

    2015-08-01

    The hallmarks of cancer currently define the molecular mechanisms responsible for conferring specific tumor phenotypes. Recently, these characteristics were also connected to the status of the secretory pathway, thereby linking the functionality of this cellular machinery to the acquisition of cancer cell features. The secretory pathway ensures the biogenesis of proteins that are membrane-bound or secreted into the extracellular milieu and can control its own homeostasis through an adaptive signaling pathway named the unfolded protein response (UPR). In the present review, we discuss the specific features of the UPR in various tumor types and the impact of the selective activation of this pathway on cell transformation, tumor development and aggressiveness.

  14. Thermal adaptability of Kluyveromyces marxianus in recombinant protein production

    PubMed Central

    2013-01-01

    Background Kluyveromyces marxianus combines the ease of genetic manipulation and fermentation with the ability to efficiently secrete high molecular weight proteins, performing eukaryotic post-translational modifications. It is able to grow efficiently in a wide range of temperatures. The secretion performances were analyzed in the host K. marxianus L3 in the range between 5°C and 40°C by means of 3 different reporter proteins, since temperature appears a key parameter for production and secretion of recombinant proteins. Results The recombinant strains were able to grow up to 40°C and, along the tested temperature interval (5-40°C), the specific growth rates (μ) were generally lower as compared to those of the untransformed strain. Biomass yields were slightly affected by temperature, with the highest values reached at 15°C and 30°C. The secretion of the endogenous β-fructofuranosidase, used as an internal control, was efficient in the range of the tested temperature, as evaluated by assaying the enzyme activity in the culture supernatants. The endogenous β-fructofuranosidase production was temperature dependent, with the highest yield at 30°C. The heterologous proteins HSA, GAA and Sod1p were all successfully produced and secreted between 5°C and 40°C, albeit each one presented a different optimal production temperature (15, 40, 5-30°C for HSA, GAA and Sod1p, respectively). Conclusions K. marxianus L3 has been identified as a promising and flexible cell factory. In a sole host, the optimization of growth temperatures for the efficient secretion of each individual protein can be carried out over a wide range of temperatures. PMID:23587421

  15. Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates – A Substudy

    PubMed Central

    Hursel, Rick; Martens, Eveline A. P.; Gonnissen, Hanne K. J.; Hamer, Henrike M.; Senden, Joan M. G.; van Loon, Luc J. C.; Westerterp-Plantenga, Margriet S.

    2015-01-01

    Background Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. Objective To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. Methods A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. Results After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low

  16. Adaptive Protein Evolution in Animals and the Effective Population Size Hypothesis

    PubMed Central

    Galtier, Nicolas

    2016-01-01

    The rate at which genomes adapt to environmental changes and the prevalence of adaptive processes in molecular evolution are two controversial issues in current evolutionary genetics. Previous attempts to quantify the genome-wide rate of adaptation through amino-acid substitution have revealed a surprising diversity of patterns, with some species (e.g. Drosophila) experiencing a very high adaptive rate, while other (e.g. humans) are dominated by nearly-neutral processes. It has been suggested that this discrepancy reflects between-species differences in effective population size. Published studies, however, were mainly focused on model organisms, and relied on disparate data sets and methodologies, so that an overview of the prevalence of adaptive protein evolution in nature is currently lacking. Here we extend existing estimators of the amino-acid adaptive rate by explicitly modelling the effect of favourable mutations on non-synonymous polymorphism patterns, and we apply these methods to a newly-built, homogeneous data set of 44 non-model animal species pairs. Data analysis uncovers a major contribution of adaptive evolution to the amino-acid substitution process across all major metazoan phyla—with the notable exception of humans and primates. The proportion of adaptive amino-acid substitution is found to be positively correlated to species effective population size. This relationship, however, appears to be primarily driven by a decreased rate of nearly-neutral amino-acid substitution because of more efficient purifying selection in large populations. Our results reveal that adaptive processes dominate the evolution of proteins in most animal species, but do not corroborate the hypothesis that adaptive substitutions accumulate at a faster rate in large populations. Implications regarding the factors influencing the rate of adaptive evolution and positive selection detection in humans vs. other organisms are discussed. PMID:26752180

  17. The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response.

    PubMed

    Gilli, Francesca; Li, Libin; Pachner, Andrew R

    2016-02-01

    Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD. Also, we measured 32 cytokines/chemokines by multiplex Luminex analysis in CSF specimens from early and late TMEV-IDD as well as sham-treated mice. Results indicate that, in the later stage of TMEV-IDD, activation of the innate immune response is most prominent: TLRs, type I IFN response genes, and innate immunity-associated cytokines were highly expressed in late TMEV-IDD compared to sham (p ≤ 0.0001) and early TMEV-IDD (p < 0.05). Conversely, several molecular mediators of adaptive immune response were highly expressed in early TMEV-IDD (all p ≤ 0.001). Protein detection in the CSF was broadly concordant with mRNA abundance of the corresponding gene measured by real-time RT-PCR in the spinal cord, since several cytokines/chemokines were increased in the CSF of TMEV-IDD mice. Results show a clear shift from adaptive to innate immunity from early to late TMEV-IDD, indicating that adaptive and innate immune pathways are likely involved in the development and progression of the disease to different extents. CSF provides an optimal source of biomarkers of CNS neuroinflammation.

  18. SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

    PubMed Central

    Kuennen, M.; Gourley, C.; Schneider, S.; Dokladny, K.; Moseley, P.

    2013-01-01

    Introduction Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs). Salivary IgA (IgA) has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys) and lactoferrin (Lac). Objective To determine the effect of a 50-km trail race on salivary cortisol (Cort), IgA, Lys, and Lac. Methods 14 subjects: (6 females, 8 males) completed a 50km ultramarathon. Saliva was collected pre, immediately after (post) and 1.5 hrs post race (+1.5). Results Lac concentration was higher at +1.5 hrs post race compared to post exercise (p < 0.05). Lys was unaffected by the race (p > 0.05). IgA concentration, secretion rate, and IgA/Osm were lower +1.5 hrs post compared to pre race (p < 0.05). Cort concentration was higher at post compared to +1.5 (p < 0.05), but was unaltered from pre race levels. Subjects finished in 7.81±1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p < 0.05) compared to pre race. Conclusions The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running. PMID:24744458

  19. Differential Molecular Responses of Rapeseed Cotyledons to Light and Dark Reveal Metabolic Adaptations toward Autotrophy Establishment

    PubMed Central

    He, Dongli; Damaris, Rebecca N.; Fu, Jinlei; Tu, Jinxing; Fu, Tingdong; Xi, Chen; Yi, Bin; Yang, Pingfang

    2016-01-01

    Photosynthesis competent autotrophy is established during the postgerminative stage of plant growth. Among the multiple factors, light plays a decisive role in the switch from heterotrophic to autotrophic growth. Under dark conditions, the rapeseed hypocotyl extends quickly with an apical hook, and the cotyledon is yellow and folded, and maintains high levels of the isocitrate lyase (ICL). By contrast, in the light, the hypocotyl extends slowly, the cotyledon unfolds and turns green, the ICL content changes in parallel with cotyledon greening. To reveal metabolic adaptations during the establishment of postgerminative autotrophy in rapeseed, we conducted comparative proteomic and metabolomic analyses of the cotyledons of seedlings grown under light versus dark conditions. Under both conditions, the increase in proteases, fatty acid β-oxidation and glyoxylate-cycle related proteins was accompanied by rapid degradation of the stored proteins and lipids with an accumulation of the amino acids. While light condition partially retarded these conversions. Light significantly induced the expression of chlorophyll-binding and photorespiration related proteins, resulting in an increase in reducing-sugars. However, the levels of some chlorophyllide conversion, Calvin-cycle and photorespiration related proteins also accumulated in dark grown cotyledons, implying that the transition from heterotrophy to autotrophy is programmed in the seed rather than induced by light. Various anti-stress systems, e.g., redox related proteins, salicylic acid, proline and chaperones, were employed to decrease oxidative stress, which was mainly derived from lipid oxidation or photorespiration, under both conditions. This study provides a comprehensive understanding of the differential molecular responses of rapeseed cotyledons to light and dark conditions, which will facilitate further study on the complex mechanism underlying the transition from heterotrophy to autotrophy. PMID:27471506

  20. Protein Secondary Structure Prediction Using Local Adaptive Techniques in Training Neural Networks

    NASA Astrophysics Data System (ADS)

    Aik, Lim Eng; Zainuddin, Zarita; Joseph, Annie

    2008-01-01

    One of the most significant problems in computer molecular biology today is how to predict a protein's three-dimensional structure from its one-dimensional amino acid sequence or generally call the protein folding problem and difficult to determine the corresponding protein functions. Thus, this paper involves protein secondary structure prediction using neural network in order to solve the protein folding problem. The neural network used for protein secondary structure prediction is multilayer perceptron (MLP) of the feed-forward variety. The training set are taken from the protein data bank which are 120 proteins while 60 testing set is the proteins which were chosen randomly from the protein data bank. Multiple sequence alignment (MSA) is used to get the protein similar sequence and Position Specific Scoring matrix (PSSM) is used for network input. The training process of the neural network involves local adaptive techniques. Local adaptive techniques used in this paper comprises Learning rate by sign changes, SuperSAB, Quickprop and RPROP. From the simulation, the performance for learning rate by Rprop and Quickprop are superior to all other algorithms with respect to the convergence time. However, the best result was obtained using Rprop algorithm.

  1. Mutation of a cuticular protein, BmorCPR2, alters larval body shape and adaptability in silkworm, Bombyx mori.

    PubMed

    Qiao, Liang; Xiong, Gao; Wang, Ri-xin; He, Song-zhen; Chen, Jie; Tong, Xiao-ling; Hu, Hai; Li, Chun-lin; Gai, Ting-ting; Xin, Ya-qun; Liu, Xiao-fan; Chen, Bin; Xiang, Zhong-huai; Lu, Cheng; Dai, Fang-yin

    2014-04-01

    Cuticular proteins (CPs) are crucial components of the insect cuticle. Although numerous genes encoding cuticular proteins have been identified in known insect genomes to date, their functions in maintaining insect body shape and adaptability remain largely unknown. In the current study, positional cloning led to the identification of a gene encoding an RR1-type cuticular protein, BmorCPR2, highly expressed in larval chitin-rich tissues and at the mulberry leaf-eating stages, which is responsible for the silkworm stony mutant. In the Dazao-stony strain, the BmorCPR2 allele is a deletion mutation with significantly lower expression, compared to the wild-type Dazao strain. Dysfunctional BmorCPR2 in the stony mutant lost chitin binding ability, leading to reduced chitin content in larval cuticle, limitation of cuticle extension, abatement of cuticle tensile properties, and aberrant ratio between internodes and intersegmental folds. These variations induce a significant decrease in cuticle capacity to hold the growing internal organs in the larval development process, resulting in whole-body stiffness, tightness, and hardness, bulging intersegmental folds, and serious defects in larval adaptability. To our knowledge, this is the first study to report the corresponding phenotype of stony in insects caused by mutation of RR1-type cuticular protein. Our findings collectively shed light on the specific role of cuticular proteins in maintaining normal larval body shape and will aid in the development of pest control strategies for the management of Lepidoptera.

  2. Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis.

    PubMed

    Margolis, Lee M; Pasiakos, Stefan M

    2013-11-01

    Mitochondrial biogenesis is a critical metabolic adaptation to aerobic exercise training that results in enhanced mitochondrial size, content, number, and activity. Recent evidence has shown that dietary manipulation can further enhance mitochondrial adaptations to aerobic exercise training, which may delay skeletal muscle fatigue and enhance exercise performance. Specifically, studies have demonstrated that combining carbohydrate restriction (endogenous and exogenous) with a single bout of aerobic exercise potentiates the beneficial effects of exercise on markers of mitochondrial biogenesis. Additionally, studies have demonstrated that high-quality protein supplementation enhances anabolic skeletal muscle intracellular signaling and mitochondrial protein synthesis following a single bout of aerobic exercise. Mitochondrial biogenesis is stimulated by complex intracellular signaling pathways that appear to be primarily regulated by 5'AMP-activated protein kinase and p38 mitogen-activated protein kinase mediated through proliferator-activated γ receptor co-activator 1 α activation, resulting in increased mitochondrial DNA expression and enhanced skeletal muscle oxidative capacity. However, the mechanisms by which concomitant carbohydrate restriction and dietary protein supplementation modulates mitochondrial adaptations to aerobic exercise training remains unclear. This review summarizes intracellular regulation of mitochondrial biogenesis and the effects of carbohydrate restriction and protein supplementation on mitochondrial adaptations to aerobic exercise.

  3. High-resolution mapping of protein concentration reveals principles of proteome architecture and adaptation.

    PubMed

    Levy, Emmanuel D; Kowarzyk, Jacqueline; Michnick, Stephen W

    2014-05-22

    A single yeast cell contains a hundred million protein molecules. How these proteins are organized to orchestrate living processes is a central question in biology. To probe this organization in vivo, we measured the local concentration of proteins based on the strength of their nonspecific interactions with a neutral reporter protein. We first used a cytosolic reporter and measured local concentrations for ~2,000 proteins in S. cerevisiae, with accuracy comparable to that of mass spectrometry. Localizing the reporter to membranes specifically increased the local concentration measured for membrane proteins. Comparing the concentrations measured by both reporters revealed that encounter frequencies between proteins are primarily dictated by their abundances. However, to change these encounter frequencies and restructure the proteome, as in adaptation, we find that changes in localization have more impact than changes in abundance. These results highlight how protein abundance and localization contribute to proteome organization and reorganization.

  4. Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma

    PubMed Central

    Capaldo, Brian J.; Roller, Devin; Axelrod, Mark J.; Koeppel, Alex F.; Petricoin, Emanuel F.; Slingluff, Craig L.; Weber, Michael J.; Mackey, Aaron J.; Gioeli, Daniel; Bekiranov, Stefan

    2015-01-01

    Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to mitogen-activated protein kinase (MAPK) pathway inhibition, we identified the combination of PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ErbB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. To identify potential mechanisms of resistance to PLX4720 treatment and synergy with lapatinib treatment, we performed a multi-platform functional genomics analysis to profile the genome as well as the transcriptional and proteomic responses of these cell lines to treatment with PLX4720. We found modest levels of resistance correlated with the zygosity of the BRAF V600E allele and receptor tyrosine kinase (RTK) mutational status. Layered over base-line resistance was substantial upregulation of many ErbB pathway genes in response to BRaf inhibition, thus generating the vulnerability to combination with lapatinib. The transcriptional responses of ErbB pathway genes are associated with a number of transcription factors, including ETS2 and its associated cofactors that represent a convergent regulatory mechanism conferring synergistic drug susceptibility in the context of diverse mutational landscapes. PMID:26405815

  5. Adaptive response to hydrogen peroxide in yeast: induction, time course, and relationship to dose-response models.

    PubMed

    Hoffmann, George R; Moczula, Andrew V; Laterza, Amanda M; Macneil, Lindsey K; Tartaglione, Jason P

    2013-07-01

    The assay for trp5 gene conversion and ilv1-92 reversion in Saccharomyces cerevisiae strain D7 was used to characterize the induction of an adaptive response by hydrogen peroxide (H(2)O(2)). Effects of a small priming dose on the genotoxic effects of a larger challenge dose were measured in exponential cultures and in early stationary phase. An adaptive response, indicated by smaller convertant and revertant frequencies after the priming dose, occurred at lower priming and challenge doses in young, well-aerated cultures. Closely spaced priming doses from 0.000975 to 2 mM, followed by a 1 mM challenge, showed that the induction of the adaptive response is biphasic. In exponential cultures it was maximal with a priming dose of 0.125-0.25 mM. Very small priming doses were insufficient to induce the adaptive response, whereas higher doses contributed to damage. A significant adaptive response was detected when the challenge dose was administered 10-20 min after the priming exposure. It was fully expressed within 45 min, and the yeast began to return to the nonadapted state after 4-6 hr. Because of the similarity of the biphasic induction to hormetic curves and the proposal that adaptive responses are a manifestation of hormesis, we evaluated whether the low doses of H(2)O(2) that induce the adaptive response show a clear hormetic response without a subsequent challenge dose. Hormesis was not evident, but there was an apparent threshold for genotoxicity at or slightly below 0.125 mM. The results are discussed with respect to linear, threshold, and hormesis dose-response models.

  6. The effect of prism adaptation on the response AC/A ratio.

    PubMed

    Rainey, B B

    2000-05-01

    Vergence adaptation, also known as prism adaptation, is a phenomenon in which a patient's heterophoria changes after prolonged viewing through prism. The effect of prism adaptation on the accommodation-convergence relationship, quantified by the AC/A ratio, is not known. Previous studies of AC/A ratio stability and alterability have used only stimulus AC/A ratio calculations, or have measured accommodative responses to only one or two stimuli. The ideal study of AC/A ratio stability and alterability would measure accommodative responses to several accommodative stimuli, and use these along with vergence responses to calculate response AC/A ratios, rather than stimulus AC/A ratios. In addition, the gradient method should be used to avoid any effect of proximal vergence resulting from changes in target distance. This paper describes a project which investigated the effect of vergence (prism) adaptation on the gradient response AC/A ratio, using accommodative responses measured for five different accommodative stimuli. The response AC/A ratio did not significantly change following a period of adaptation to base-in prism for six of the eight subjects in this study. In addition, the response AC/A ratio did not significantly change following a period of adaptation to base-out prism for six of the eight subjects.

  7. Compensatory structural adaptive modifications of vagina in response to functional demand in goat.

    PubMed

    Hussin, Amer M; Zaid, Nazih W; Hussain, S O

    2014-01-01

    Vaginal biopsies and smears were collected from ten adult local healthy goats. Routine histological methods were carried out on vaginal biopsies and then stained with PAS stain. The smears were stained with Methylene blue. All samples were inspected under light microscope. The present study found that many constituents of the wall of the vagina, which have an important functional role, were absent; among these were the vaginal glands, goblet cells, muscularis mucosa, and lymphatic nodules. On the other hand, vagina showed special compensatory histological mechanisms, namely, the deep epithelial folds, the well-developed germinated stratum basale, the apparent basement membrane, and the profuse defensive cells, such as neutrophils, macrophages, lymphocytes, plasma cells, and mast cells. The general stains of this study could not recognize dendritic cells although they play an important functional role. Moreover, the herein study declared also that the vaginal smears showing many adaptive cellular mechanisms among these were, the keratinization, the process of sheet formation that lines the vaginal lumen, the process of metachromasia which is related to the cellular activity in protein synthesis, keratin, and finally the presence of endogenous microorganisms. It was concluded that all the above cellular compensatory adaptive mechanisms may compensate the lacking vaginal constituents and act to raise the immune response of the vagina.

  8. Energy Sector Adaptation in Response to Water Scarcity

    NASA Astrophysics Data System (ADS)

    Johnson, N. A.; Fricko, O.; Parkinson, S.; Riahi, K.

    2015-12-01

    Global energy systems models have largely ignored the impacts of water scarcity on the energy sector and the related implications for climate change mitigation. However, significant water is required in the production of energy, including for thermoelectric power plant cooling, hydropower generation, irrigation for bioenergy, and the extraction and refining of liquid fuels. With a changing climate and expectations of increasing competition for water from the agricultural and municipal sectors, it is unclear whether sufficient water will be available where needed to support water-intensive energy technologies in the future. Thus, it is important that water use and water constraints are incorporated into energy systems models to better understand energy sector adaptation to water scarcity. The global energy systems model, MESSAGE, has recently been updated to quantify the water consumption and withdrawal requirements of the energy sector and now includes several cooling technologies for addressing water scarcity. This study introduces water constraints into the model to examine whether and how the energy sector can adapt to water scarcity over the next century. In addition, the implications for climate mitigation are evaluated under a scenario in which warming is limited to 2˚C over the pre-industrial level. Given the difficulty of introducing meaningful water constraints into global models, we use a simplistic approach and evaluate a series of scenarios in which the water available to the energy sector is systematically reduced. This approach allows for the evaluation of energy sector adaptations under various levels of water scarcity and can provide insight into how water scarcity, whether from climate change or competing demands, may impact the energy sector in different world regions. This study will provide insight into the following questions: How does the energy sector adapt to water scarcity in different regions? What are the costs associated with adaptation

  9. Adaptive immune response to lipoproteins of Staphylococcus aureus in healthy subjects

    PubMed Central

    Vu, Chi Hai; Kolata, Julia; Stentzel, Sebastian; Beyer, Anica; Gesell Salazar, Manuela; Steil, Leif; Pané‐Farré, Jan; Rühmling, Vanessa; Engelmann, Susanne; Götz, Friedrich; van Dijl, Jan Maarten; Hecker, Michael; Mäder, Ulrike; Schmidt, Frank; Völker, Uwe

    2016-01-01

    Staphylococcus aureus is a frequent commensal but also a dangerous pathogen, causing many forms of infection ranging from mild to life‐threatening conditions. Among its virulence factors are lipoproteins, which are anchored in the bacterial cell membrane. Lipoproteins perform various functions in colonization, immune evasion, and immunomodulation. These proteins are potent activators of innate immune receptors termed Toll‐like receptors 2 and 6. This study addressed the specific B‐cell and T‐cell responses directed to lipoproteins in human S. aureus carriers and non‐carriers. 2D immune proteomics and ELISA approaches revealed that titers of antibodies (IgG) binding to S. aureus lipoproteins were very low. Proliferation assays and cytokine profiling data showed only subtle responses of T cells; some lipoproteins did not elicit proliferation. Hence, the robust activation of the innate immune system by S. aureus lipoproteins does not translate into a strong adaptive immune response. Reasons for this may include inaccessibility of lipoproteins for B cells as well as ineffective processing and presentation of the antigens to T cells. PMID:27324828

  10. Adaptability: Conceptual and Empirical Perspectives on Responses to Change, Novelty and Uncertainty

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry; Colmar, Susan; Liem, Gregory Arief D.

    2012-01-01

    Adaptability is proposed as individuals' capacity to constructively regulate psycho-behavioral functions in response to new, changing, and/or uncertain circumstances, conditions and situations. The present investigation explored the internal and external validity of an hypothesised adaptability scale. The sample comprised 2,731 high school…

  11. Modulation of host adaptive immunity by hRSV proteins

    PubMed Central

    Espinoza, Janyra A; Bohmwald, Karen; Céspedes, Pablo F; Riedel, Claudia A; Bueno, Susan M; Kalergis, Alexis M

    2014-01-01

    Globally, the human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infections (LRTIs) in infants and children younger than 2 years old. Furthermore, the number of hospitalizations due to LRTIs has shown a sustained increase every year due to the lack of effective vaccines against hRSV. Thus, this virus remains as a major public health and economic burden worldwide. The lung pathology developed in hRSV-infected humans is characterized by an exacerbated inflammatory and Th2 immune response. In order to rationally design new vaccines and therapies against this virus, several studies have focused in elucidating the interactions between hRSV virulence factors and the host immune system. Here, we discuss the main features of hRSV biology, the processes involved in virus recognition by the immune system and the most relevant mechanisms used by this pathogen to avoid the antiviral host response. PMID:25513775

  12. The effect of repeated mild cold water immersions on the adaptation of the vasomotor responses

    NASA Astrophysics Data System (ADS)

    Wakabayashi, Hitoshi; Wijayanto, Titis; Kuroki, Hideto; Lee, Joo-Young; Tochihara, Yutaka

    2012-07-01

    There are several types of cold adaptation based on the alteration of thermoregulatory response. It has been thought that the temperature of repeated cold exposures during the adaptation period is one of the factors affecting the type of cold adaptation developed. This study tested the hypothesis that repeated mild cold immersions would induce an insulative cold adaptation but would not alter the metabolic response. Seven healthy male participants were immersed to their xiphoid process level repeatedly in 26°C water for 60 min, 3 days every week, for 4 weeks. During the first and last exposure of this cold acclimation period, the participants underwent body immersion tests measuring their thermoregulatory responses to cold. Separately, they conducted finger immersion into 5°C water for 30 min to assess their cold-induced vasodilation (CIVD) response before and after cold acclimation. During the immersion to xiphoid process, participants showed significantly lower mean skin temperature and skin blood flow in the forearm post-acclimation, while no adaptation was observed in the metabolic response. Additionally, blunted CIVD responses were observed after cold acclimation. From these results, it was considered that the participants showed an insulative-type of cold acclimation after the repeated mild cold immersions. The major finding of this study was the acceptance of the hypothesis that repeated mild cold immersion was sufficient to induce insulative cold adaptation but did not alter the metabolic response. It is suggested that the adaptation in the thermoregulatory response is specific to the response which is repeatedly stimulated during the adaptation process.

  13. Whether Plant Responses to Microgravity are Adaptive in Full or in Part.

    NASA Astrophysics Data System (ADS)

    Kordyum, Elizabeth

    F1.1 Microgravity is well known to be an unusual factor for plant but plants grow and develop in space flight from seed-to-seed, as it has been perfectly shown in the experiments aboard shut-tle Columbia (STS-87) and ISS. Under the more or less optimal conditions for plant growing, namely temperature, humidity, CO2, light intensity and directivity, in the hardware, high-quality seeds germinate one hundred percent.. Cytological studies of plants developing in real and simulated microgravity made it possible to establish that the processes of mitosis, cytoki-nesis, and tissue differentiation of vegetative and generative organs are largely normal. The patterns of histogenesis and cell differentiation established for root caps in microgravity lead to the conclusion that the graviperceptive apparatus of the intact embryonic roots has formed but does not function in the absence of a gravitational vector. Normal space orientation of plant organs is provided by autotropism and phototropism. At the same time, under micro-gravity, essential reconstruction in the structural and functional organization of cell organelles and cytoskeleton, as well as changes in cell metabolism and homeostasis have been described. In addition, new interesting data concerning the influence of altered gravity on lipid peroxi-dation intensity, the level of reactive oxygen species, and antioxidant system activity, just like on the level of gene expression and synthesis of low-molecular and high-molecular heat shock proteins were recently obtained Available experimental data are discussed in the light of notions on adaptive syndrome in plants. The dynamics of the observable patterns demonstrate that adaptation occurs on the principle of self-regulating systems within the physiological response limits.. However, a delay in synthesis of storage nutrients and the lower level its accumulation in seeds in microgravty, as well as the formation of seeds with anomalous embryos in some cases made it

  14. Clinal adaptation and adaptive plasticity in Artemisia californica: implications for the response of a foundation species to predicted climate change.

    PubMed

    Pratt, Jessica D; Mooney, Kailen A

    2013-08-01

    Local adaptation and plasticity pose significant obstacles to predicting plant responses to future climates. Although local adaptation and plasticity in plant functional traits have been documented for many species, less is known about population-level variation in plasticity and whether such variation is driven by adaptation to environmental variation. We examined clinal variation in traits and performance - and plastic responses to environmental change - for the shrub Artemisia californica along a 700 km gradient characterized (from south to north) by a fourfold increase in precipitation and a 61% decrease in interannual precipitation variation. Plants cloned from five populations along this gradient were grown for 3 years in treatments approximating the precipitation regimes of the north and south range margins. Most traits varying among populations did so clinally; northern populations (vs. southern) had higher water-use efficiencies and lower growth rates, C : N ratios and terpene concentrations. Notably, there was variation in plasticity for plant performance that was strongly correlated with source site interannual precipitation variability. The high-precipitation treatment (vs. low) increased growth and flower production more for plants from southern populations (181% and 279%, respectively) than northern populations (47% and 20%, respectively). Overall, precipitation variability at population source sites predicted 86% and 99% of variation in plasticity in growth and flowering, respectively. These striking, clinal patterns in plant traits and plasticity are indicative of adaptation to both the mean and variability of environmental conditions. Furthermore, our analysis of long-term coastal climate data in turn indicates an increase in interannual precipitation variation consistent with most global change models and, unexpectedly, this increased variation is especially pronounced at historically stable, northern sites. Our findings demonstrate the

  15. The adaptive response of bacterial food-borne pathogens in the environment, host and food: Implications for food safety.

    PubMed

    Alvarez-Ordóñez, Avelino; Broussolle, Véronique; Colin, Pierre; Nguyen-The, Christophe; Prieto, Miguel

    2015-11-20

    Bacteria are constantly faced to stress situations in their ecological niches, the food and the host gastrointestinal tract. The capacity to detect and respond to surrounding changes is crucial for bacterial pathogens to survive or grow in changing environments. To this purpose, cells have evolved various sophisticated networks designed to protect against stressors or repair damage caused by them. Challenges can occur during production of foods when subjected to processing, and after food ingestion when confronted with host defensive barriers. Some pathogenic bacteria have shown the capacity to develop stable resistance against extreme conditions within a defined genomic context and a limited number of generations. On the other hand, bacteria can also respond to adverse conditions in a transient manner, through the so-called stress tolerance responses. Bacterial stress tolerance responses include both structural and physiological modifications in the cell and are mediated by complex genetic regulatory machinery. Major aspects in the adaptive response are the sensing mechanisms, the characterization of cell defensive systems, such as the operation of regulatory proteins (e.g. RpoS), the induction of homeostatic and repair systems, the synthesis of shock response proteins, and the modifications of cell membranes, particularly in their fatty acid composition and physical properties. This article reviews certain strategies used by food-borne bacteria to respond to particular stresses (acid, cold stress, extreme pressure) in a permanent or transient manner and discusses the implications that such adaptive responses pose for food safety.

  16. Engineering of chaperone systems and of the unfolded protein response

    PubMed Central

    Khan, Saeed U.

    2008-01-01

    Production of recombinant proteins in mammalian cells is a successful technology that delivers protein pharmaceuticals for therapies and for diagnosis of human disorders. Cost effective production of protein biopharmaceuticals requires extensive optimization through cell and fermentation process engineering at the upstream and chemical engineering of purification processes at the downstream side of the production process. The majority of protein pharmaceuticals are secreted proteins. Accumulating evidence suggests that the folding and processing of these proteins in the endoplasmic reticulum (ER) is a general rate- and yield limiting step for their production. We will summarize our knowledge of protein folding in the ER and of signal transduction pathways activated by accumulation of unfolded proteins in the ER, collectively called the unfolded protein response (UPR). On the basis of this knowledge we will evaluate engineering approaches to increase cell specific productivities through engineering of the ER-resident protein folding machinery and of the UPR. PMID:19003179

  17. Adaptive responses to dasatinib-treated lung squamous cell cancer cells harboring DDR2 mutations.

    PubMed

    Bai, Yun; Kim, Jae-Young; Watters, January M; Fang, Bin; Kinose, Fumi; Song, Lanxi; Koomen, John M; Teer, Jamie K; Fisher, Kate; Chen, Yian Ann; Rix, Uwe; Haura, Eric B

    2014-12-15

    DDR2 mutations occur in approximately 4% of lung squamous cell cancer (SCC) where the tyrosine kinase inhibitor dasatinib has emerged as a new therapeutic option. We found that ERK and AKT phosphorylation was weakly inhibited by dasatinib in DDR2-mutant lung SCC cells, suggesting that dasatinib inhibits survival signals distinct from other oncogenic receptor tyrosine kinases (RTK) and/or compensatory signals exist that dampen dasatinib activity. To gain better insight into dasatinib's action in these cells, we assessed altered global tyrosine phosphorylation (pY) after dasatinib exposure using a mass spectrometry-based quantitative phosphoproteomics approach. Overlaying protein-protein interaction relationships upon this dasatinib-regulated pY network revealed decreased phosphorylation of Src family kinases and their targets. Conversely, dasatinib enhanced tyrosine phosphorylation in a panel of RTK and their signaling adaptor complexes, including EGFR, MET/GAB1, and IGF1R/IRS2, implicating a RTK-driven adaptive response associated with dasatinib. To address the significance of this observation, these results were further integrated with results from a small-molecule chemical library screen. We found that dasatinib combined with MET and insulin-like growth factor receptor (IGF1R) inhibitors had a synergistic effect, and ligand stimulation of EGFR and MET rescued DDR2-mutant lung SCC cells from dasatinib-induced loss of cell viability. Importantly, we observed high levels of tyrosine-phosphorylated EGFR and MET in a panel of human lung SCC tissues harboring DDR2 mutations. Our results highlight potential RTK-driven adaptive-resistant mechanisms upon DDR2 targeting, and they suggest new, rationale cotargeting strategies for DDR2-mutant lung SCC.

  18. Measuring and Detecting Molecular Adaptation in Codon Usage Against Nonsense Errors During Protein Translation

    PubMed Central

    Gilchrist, Michael A.; Shah, Premal; Zaretzki, Russell

    2009-01-01

    Codon usage bias (CUB) has been documented across a wide range of taxa and is the subject of numerous studies. While most explanations of CUB invoke some type of natural selection, most measures of CUB adaptation are heuristically defined. In contrast, we present a novel and mechanistic method for defining and contextualizing CUB adaptation to reduce the cost of nonsense errors during protein translation. Using a model of protein translation, we develop a general approach for measuring the protein production cost in the face of nonsense errors of a given allele as well as the mean and variance of these costs across its coding synonyms. We then use these results to define the nonsense error adaptation index (NAI) of the allele or a contiguous subset thereof. Conceptually, the NAI value of an allele is a relative measure of its elevation on a specific and well-defined adaptive landscape. To illustrate its utility, we calculate NAI values for the entire coding sequence and across a set of nonoverlapping windows for each gene in the Saccharomyces cerevisiae S288c genome. Our results provide clear evidence of adaptation to reduce the cost of nonsense errors and increasing adaptation with codon position and expression. The magnitude and nature of this adaptation are also largely consistent with simulation results in which nonsense errors are the only selective force driving CUB evolution. Because NAI is derived from mechanistic models, it is both easier to interpret and more amenable to future refinement than other commonly used measures of codon bias. Further, our approach can also be used as a starting point for developing other mechanistically derived measures of adaptation such as for translational accuracy. PMID:19822731

  19. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress.

    PubMed

    Klatt, P; Lamas, S

    2000-08-01

    Protein S-glutathiolation, the reversible covalent addition of glutathione to cysteine residues on target proteins, is emerging as a candidate mechanism by which both changes in the intracellular redox state and the generation of reactive oxygen and nitrogen species may be transduced into a functional response. This review will provide an introduction to the concepts of oxidative and nitrosative stress and outline the molecular mechanisms of protein regulation by oxidative and nitrosative thiol-group modifications. Special attention will be paid to recently published work supporting a role for S-glutathiolation in stress signalling pathways and in the adaptive cellular response to oxidative and nitrosative stress. Finally, novel insights into the molecular mechanisms of S-glutathiolation as well as methodological problems related to the interpretation of the biological relevance of this post-translational protein modification will be discussed.

  20. Metabolic and proteomic study of NS0 myeloma cell line following the adaptation to protein-free medium.

    PubMed

    de la Luz-Hernández, K R; Rojas-del Calvo, L; Rabasa-Legón, Y; Lage-Castellanos, A; Castillo-Vitlloch, A; Díaz, J; Gaskell, S

    2008-07-21

    Proteomics and metabolomics technologies are potentially useful tool for the study of the very complex process of cell adaptation to protein-free medium. In this work, we used the iTRAQ technology to analyze different protein levels in adapted and non-adapted NS0 myeloma cell line. Several proteins with differential expression profile were characterized and quantified. Carbohydrate metabolism, protein synthesis and membrane transport were the principal pathways that change after the adaptation. Changes in lactate production rate with respect to glucose consumption rate were observed according to the changes observed by proteomic.

  1. Apnea stimulates the adaptive response to oxidative stress in elephant seal pups.

    PubMed

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Tift, Michael S; Forman, Henry Jay; Crocker, Daniel E; Ortiz, Rudy M

    2011-12-15

    Extended breath-hold (apnea) bouts are routine during diving and sleeping in seals. These apneas result in oxygen store depletion and blood flow redistribution towards obligatory oxygen-dependent tissues, exposing seals to critical levels of ischemia and hypoxemia. The subsequent reperfusion/reoxygenation has the potential to increase oxidant production and thus oxidative stress. The contributions of extended apnea to oxidative stress in adapted mammals are not well defined. To address the hypothesis that apnea in seals is not associated with increased oxidative damage, blood samples were collected from northern elephant seal pups (N=6) during eupnea, rest- and voluntary submersion-associated apneas, and post-apnea (recovery). Plasma 4-hydroxynonenal (HNE), 8-isoprostanes (8-isoPGF(2α)), nitrotyrosine (NT), protein carbonyls, xanthine and hypoxanthine (HX) levels, along with xanthine oxidase (XO) activity, were measured. Protein content of XO, superoxide dismutase 1 (Cu,ZnSOD), catalase and myoglobin (Mb), as well as the nuclear content of hypoxia inducible factor 1α (HIF-1α) and NF-E2-related factor 2 (Nrf2), were measured in muscle biopsies collected before and after the breath-hold trials. HNE, 8-iso PGF(2α), NT and protein carbonyl levels did not change among eupnea, apnea or recovery. XO activity and HX and xanthine concentrations were increased at the end of the apneas and during recovery. Muscle protein content of XO, CuZnSOD, catalase, Mb, HIF-1α and Nrf2 increased 25-70% after apnea. Results suggest that rather than inducing the damaging effects of hypoxemia and ischemia/reperfusion that have been reported in non-diving mammals, apnea in seals stimulates the oxidative stress and hypoxic hormetic responses, allowing these mammals to cope with the potentially detrimental effects associated with this condition.

  2. Reactive oxygen species-mediated unfolded protein response pathways in preimplantation embryos

    PubMed Central

    Ali, Ihsan; Shah, Syed Zahid Ali; Jin, Yi; Li, Zhong-Shu; Ullah, Obaid

    2017-01-01

    Excessive production of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress-mediated responses are critical to embryonic development in the challenging in vitro environment. ROS production increases during early embryonic development with the increase in protein requirements for cell survival and growth. The ER is a multifunctional cellular organelle responsible for protein folding, modification, and cellular homeostasis. ER stress is activated by a variety of factors including ROS. Such stress leads to activation of the adaptive unfolded protein response (UPR), which restores homeostasis. However, chronic stress can exceed the toleration level of the ER, resulting in cellular apoptosis. In this review, we briefly describe the generation and impact of ROS in preimplantation embryo development, the ROS-mediated activation mechanism of the UPR via the ER, and the subsequent activation of signaling pathways following ER stress in preimplantation embryos. PMID:28057903

  3. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    SciTech Connect

    Miyata, Ryohei; Eeden, Stephan F. van

    2011-12-15

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}m or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  4. New insights into the unfolded protein response in stem cells.

    PubMed

    Yang, Yanzhou; Cheung, Hoi Hung; Tu, JiaJie; Miu, Kai Kei; Chan, Wai Yee

    2016-08-16

    The unfolded protein response (UPR) is an evolutionarily conserved adaptive mechanism to increase cell survival under endoplasmic reticulum (ER) stress conditions. The UPR is critical for maintaining cell homeostasis under physiological and pathological conditions. The vital functions of the UPR in development, metabolism and immunity have been demonstrated in several cell types. UPR dysfunction activates a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease and immune disease. Stem cells with the special ability to self-renew and differentiate into various somatic cells have been demonstrated to be present in multiple tissues. These cells are involved in development, tissue renewal and certain disease processes. Although the role and regulation of the UPR in somatic cells has been widely reported, the function of the UPR in stem cells is not fully known, and the roles and functions of the UPR are dependent on the stem cell type. Therefore, in this article, the potential significances of the UPR in stem cells, including embryonic stem cells, tissue stem cells, cancer stem cells and induced pluripotent cells, are comprehensively reviewed. This review aims to provide novel insights regarding the mechanisms associated with stem cell differentiation and cancer pathology.

  5. New insights into the unfolded protein response in stem cells

    PubMed Central

    Yang, Yanzhou; Cheung, Hoi Hung; Tu, JiaJie; Miu, Kai Kei; Chan, Wai Yee

    2016-01-01

    The unfolded protein response (UPR) is an evolutionarily conserved adaptive mechanism to increase cell survival under endoplasmic reticulum (ER) stress conditions. The UPR is critical for maintaining cell homeostasis under physiological and pathological conditions. The vital functions of the UPR in development, metabolism and immunity have been demonstrated in several cell types. UPR dysfunction activates a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease and immune disease. Stem cells with the special ability to self-renew and differentiate into various somatic cells have been demonstrated to be present in multiple tissues. These cells are involved in development, tissue renewal and certain disease processes. Although the role and regulation of the UPR in somatic cells has been widely reported, the function of the UPR in stem cells is not fully known, and the roles and functions of the UPR are dependent on the stem cell type. Therefore, in this article, the potential significances of the UPR in stem cells, including embryonic stem cells, tissue stem cells, cancer stem cells and induced pluripotent cells, are comprehensively reviewed. This review aims to provide novel insights regarding the mechanisms associated with stem cell differentiation and cancer pathology. PMID:27304053

  6. The unfolded protein response (UPR) pathway in Cryptococcus

    PubMed Central

    Cheon, Seon Ah; Jung, Kwang-Woo; Bahn, Yong-Sun; Kang, Hyun Ah

    2014-01-01

    Unique and evolutionarily conserved signaling pathways allow an organism to sense, respond to, and adapt to internal and external environmental cues at its biological niche. In eukaryotic cells, the unfolded protein response (UPR) pathway regulates endoplasmic reticulum (ER) homeostasis upon exposure to environmental changes causing ER stress. The UPR pathway of Cryptococcus neoformans, an opportunistic fungal pathogen, which causes life-threatening meningoencephalitis in immunocompromised individuals, consists of the evolutionarily conserved Ire1 kinase, a unique bZIP transcription factor, Hxl1, and the ER-resident molecular chaperone Kar2/BiP. Although the Cryptococcus UPR pathway regulates ER stress, antifungal drug resistance, and virulence in an Ire1/Hxl1-dependent manner, Ire1 has Hxl1-independent roles in capsule biosynthesis and thermotolerance. In this review, we highlight the conserved and unique features of the Cryptococcus UPR pathway compared with other fungal UPR systems and its importance in the pathogenesis of cryptococcosis and discuss future challenges in this field. PMID:24504058

  7. Influence of Histidine-Containing Tags on the Biodistribution of ADAPT Scaffold Proteins.

    PubMed

    Lindbo, Sarah; Garousi, Javad; Åstrand, Mikael; Honarvar, Hadis; Orlova, Anna; Hober, Sophia; Tolmachev, Vladimir

    2016-03-16

    Engineered scaffold proteins (ESP) are high-affinity binders that can be used as probes for radionuclide imaging. Histidine-containing tags enable both efficient purification of ESP and radiolabeling with (99m)Tc(CO)3. Earlier studies demonstrated that the use of a histidine-glutamate-histidine-glutamate-histidine-glutamate (HE)3-tag instead of the commonly used hexahistidine (H6)-tag reduces hepatic uptake of radiolabeled ESP and short peptides. Here, we investigated the influence of histidine-containing tags on the biodistribution of a novel type of ESP, ADAPTs. A series of anti-HER2 ADAPT probes having H6- or (HE)3-tags in the N-termini were prepared. The constructs, (HE)3-ADAPT6 and H6-ADAPT6, were labeled with two different nuclides, (99m)Tc or (111)In. The labeling with (99m)Tc(CO)3 utilized the histidine-containing tags, while (111)In was attached through a maleimido derivative of DOTA conjugated to the N-terminus. For (111)In-labeled ADAPTs, the use of (HE)3 provided a significantly (p < 0.05) lower hepatic uptake at 1 h after injection, but there was no significant difference in hepatic uptake of (111)In-(HE)3-ADAPT6 and H6-ADAPT6 at later time points. Interestingly, in the case of (99m)Tc, (99m)Tc(CO)3-H6-ADAPT6 provided significantly (p < 0.05) lower uptake in a number of normal tissues and was more suitable as an imaging probe. Thus, the influence of histidine-containing tags on the biodistribution of the novel ADAPT scaffold proteins was different compared to its influence on other ESPs studied so far. Apparently, the effect of a histidine-containing tag on the biodistribution is highly dependent on the scaffold composition of the ESP.

  8. The Stress Response Systems: Universality and Adaptive Individual Differences

    ERIC Educational Resources Information Center

    Ellis, Bruce J.; Jackson, Jenee James; Boyce, W. Thomas

    2006-01-01

    Biological reactivity to psychological stressors comprises a complex, integrated system of central neural and peripheral neuroendocrine responses designed to prepare the organism for challenge or threat. Developmental experience plays a role, along with heritable variation, in calibrating the response dynamics of this system. This calibration…

  9. Global Rsh-dependent transcription profile of Brucella suis during stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses

    PubMed Central

    2013-01-01

    Background In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatory network providing rapid adaptation to growth-affecting stress conditions such as nutrient deficiency, is essential for replication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions. Results cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wild-type and Δrsh mutant in a minimal medium, partially mimicking the nutrient-poor intramacrophagic environment. A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 198 were up-, and 181 were down-regulated. The pleiotropic character of the response was confirmed, as the genes encoded an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems, and energy metabolism proteins. Virulence genes such as narG and sodC, respectively encoding respiratory nitrate reductase and superoxide dismutase, were under the positive control of (p)ppGpp, as well as expression of the cbb3-type cytochrome c oxidase, essential for chronic murine infection. Methionine was the only amino acid whose biosynthesis was absolutely dependent on stringent response in B. suis. Conclusions The study illustrated the complexity of the processes involved in adaptation to nutrient starvation, and contributed to a better understanding of the correlation between stringent response and Brucella virulence. Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responses playing a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress. PMID:23834488

  10. Cardiovascular and organ responses and adaptation responses to hypogravity in an experimental animal model.

    NASA Astrophysics Data System (ADS)

    Biondi, R.; Capodicasa, E.; Tassi, C.; Mezzasomal, L.; Benedetti, C.; Valiani, M.; Marconi, P.; Rossi, R.

    1995-10-01

    The head-down suspension (i.e antiorthostatic hypokinesia) rat is used to simulate weightlessness. However, little is known about cardiovascular and organ adaptation responses which, over a long time, can become pathologically significant. The purpose of this study was therefore to evaluate regional changes in the hematology parameters, Endotheline-1 (ET-1) concentration and urinary excretion of N-acetyl-β-D-glucosaminidase (EC 3.2.1.30) (NAG) in an experimental antiorthostatic rat model. The data indicate significant variations in the plasma ET-1 level in time, in the superior and inferior cava vessel blood of animals maintained for 10 days in hypogravity with respect to controls. These changes do not seem to be due to hemoconcentration. The increase in urinary NAG was observed during the first 24h of experiment, indicating renal stress, probably due to adverse blood flow variations within the organ. We conclude that the plasma ET-1 level changes could be responsible, overall for the blood flow variations in the kidney and renal stress could be the consequence of extended antiorthostatic hypokinesia. The ET-1 behaviour and urinary NAG excretion in rats exposed to antiorthostatic hypokjnetic hydynamia offer possibilities for understanding if these changes might be reversible or when they become pathological. This could give some relevant information about the effects of prolonged hypogravity during the space voyage.

  11. Cardiovascular and organ responses and adaptation responses to hypogravity in an experimental animal model.

    PubMed

    Biondi, R; Capodicasa, E; Tassi, C; Mezzasoma, L; Benedetti, C; Valiani, M; Marconi, P; Rossi, R

    1995-10-01

    The head-down suspension (i.e. antiorthostatic hypokinesia) rat is used to simulate weightlessness. However, little is known about cardiovascular and organ adaptation responses which, over a long time, can become pathologically significant. The purpose of this study was therefore to evaluate regional changes in the hematology parameters. Endotheline-1 (ET-1) concentration and urinary excretion of N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) (NAG) in an experimental antiorthostatic rat model. The data indicate significant variations in the plasma ET-1 level in time, in the superior and inferior cava vessel blood of animals maintained for 10 days in hypogravity with respect to controls. These changes do not seem to be due to hemoconcentration. The increase in urinary NAG was observed during the first 24h of experiment, indicating renal stress, probably due to adverse blood flow variations within the organ. We conclude that the plasma ET-1 level changes could be responsible, overall for the blood flow variations in the kidney and renal stress could be the consequence of extended antiorthostatic hypokinesia. The ET-1 behaviour and urinary NAG excretion in rats exposed to antiorthostatic hypokinetic hydynamia offer possibilities for understanding if these changes might be reversible or when they become pathological. This could give some relevant information about the effects of prolonged hypogravity during the space voyage.

  12. PACAP is essential for the adaptive thermogenic response of brown adipose tissue to cold exposure.

    PubMed

    Diané, Abdoulaye; Nikolic, Nikolina; Rudecki, Alexander P; King, Shannon M; Bowie, Drew J; Gray, Sarah L

    2014-09-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed neuropeptide that acts as a neurotransmitter, neuromodulator, neurotropic factor, neuroprotectant, secretagogue, and neurohormone. Owing to its pleiotropic biological actions, knockout of Pacap (Adcyap1) has been shown to induce several abnormalities in mice such as impaired thermoregulation. However, the underlying physiological and molecular mechanisms remain unclear. A previous report has shown that cold-exposed Pacap null mice cannot supply appropriate levels of norepinephrine (NE) to brown adipocytes. Therefore, we hypothesized that exogenous NE would rescue the impaired thermogenic response of Pacap null mice during cold exposure. We compared the adaptive thermogenic capacity of Pacap(-/-) to Pacap(+/+) mice in response to NE when housed at room temperature (24 °C) and after a 3.5-week cold exposure (4 °C). Biochemical parameters, expression of thermogenic genes, and morphological properties of brown adipose tissue (BAT) and white adipose tissue (WAT) were also characterized. Results showed that there was a significant effect of temperature, but no effect of genotype, on the resting metabolic rate in conscious, unrestrained mice. However, the normal cold-induced increase in the basal metabolic rate and NE-induced increase in thermogenesis were severely blunted in cold-exposed Pacap(-/-) mice. These changes were associated with altered substrate utilization, reduced β3-adrenergic receptor (β3-Ar (Adrb3)) and hormone-sensitive lipase (Hsl (Lipe)) gene expression, and increased fibroblast growth factor 2 (Fgf2) gene expression in BAT. Interestingly, Pacap(-/-) mice had depleted WAT depots, associated with upregulated uncoupling protein 1 expression in inguinal WATs. These results suggest that the impairment of adaptive thermogenesis in Pacap null mice cannot be rescued by exogenous NE perhaps in part due to decreased β3-Ar-mediated BAT activation.

  13. Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis.

    PubMed

    Nirala, Niraj K; Rahman, Motiur; Walls, Stanley M; Singh, Alka; Zhu, Lihua Julie; Bamba, Takeshi; Fukusaki, Eiichiro; Srideshikan, Sargur M; Harris, Greg L; Ip, Y Tony; Bodmer, Rolf; Acharya, Usha R

    2013-06-01

    The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased

  14. Biomolecular Mechanism, Cloning, Sequencing and Analysis of Adaptive Reflection cDNAs and Proteins from Squid

    DTIC Science & Technology

    2010-05-03

    drivers of these adaptive changes in reflectance that we will investigate include electromotive ion fluxes, pH change and exposures to metal ions and...found in L. pealeii. As is the case for the other reflectin proteins (16), Ref-Lp1 and 2 contain a series of conserved subdomains (SDs). Ref-Lp1

  15. Assessment of the protein quality of 15 new northern adapted cultivars of quality protein maize using amino acid analysis.

    PubMed

    Zarkadas, C G; Hamilton, R I; Yu, Z R; Choi, V K; Khanizadeh, S; Rose, N G; Pattison, P L

    2000-11-01

    Amino acid determinations were carried out on 15 new northern adapted cultivars of quality protein maize (QPM) containing opaque-2 modifier genes to ascertain whether their amino acid scoring patterns could be used to select high-lysine QPM genotypes and to assess their protein quality. Total protein in these cultivars ranged from 8.0 to 10.2% compared to two commercial maize varieties, Dekalb DK435 (7.9%) and Pioneer 3925 (10.3%). Four of these QPM genotypes, QPM-C26, QPM-C21, QPM-C79, and QPM-C59, contained high levels of lysine (4.43-4.58 g of lysine/100 g of protein), whereas the remaining varied from 3.43 to 4.21 g of lysine/100 g of protein, compared to Dekalb DK435 and Pioneer 3925, which contained 2.9 and 3. 1 g of lysine/100 g of protein, respectively. Although lysine is the first limiting amino acid in QPM inbreds, the high-lysine QPM genotypes may supply approximately 70.2-72.6% of human protein requirements, compared to 46.2% for Dekalb DK435 and 50.1% for Pioneer 3925, 55-63% for oats, and 59-60.3% for barley. Northern adapted QPM genotypes may have the potential to increase their lysine content even further, either by an increase in specific high-lysine-containing nonzein proteins, such as the synthesis of factor EF-1a, or by a further reduction in the 19 and 22 kDa alpha-zein in the endosperm or both. This knowledge could assist maize breeders in the selection of new high-performance QPM genotypes with improved protein quality and quantity.

  16. Adaptation of Chinese hamster ovary cells to low culture temperature: cell growth and recombinant protein production.

    PubMed

    Yoon, Sung Kwan; Hong, Jong Kwang; Choo, Seung Ho; Song, Ji Yong; Park, Hong Woo; Lee, Gyun Min

    2006-04-20

    Recombinant Chinese hamster ovary (rCHO) cells producing erythropoietin (EPO) and rCHO cells producing follicle-stimulating hormone (FSH) showed a significant increase in specific productivity (q) when grown at 32 degrees C compared to 37 degrees C. However, low culture temperature suppressed cell growth, and therefore, did not increase volumetric productivity as much as q. In an attempt to increase the volumetric productivity through improvement of hypothermic growth, EPO producing rCHO (CHO-EPO) cells and FSH producing rCHO (CHO-FSH) cells were adapted at 32 degrees C in a repeated batch mode using spinner flasks. Cell growth of both CHO-EPO and CHO-FSH gradually improved during adaptation at 32 degrees C. Specific growth rates of CHO-EPO and CHO-FSH cells at 32 degrees C, through adaptation, were increased by 73% and 20%, respectively. During adaptation at 32 degrees C, mRNA levels of cold-inducible RNA-binding protein (CIRP) of both rCHO cell lines did not change significantly, suggesting that CIRP expression may not be the only cause for growth suppression at low culture temperature. Unlike cell growth, the recombinant protein production of both rCHO cell lines was not increased during adaptation due to decreased specific productivities. The specific EPO productivity and specific FSH productivity were decreased by 49% and 22%, respectively. Southern blot analyses showed that the decreased specific productivities were not due to the loss of foreign gene copies. Taken together, improvement of hypothermic cell growth by adaptation does not appear to be applicable for enhanced recombinant protein production, since specific productivity decreases during adaptation to the low culture temperature.

  17. Adaptive responses of GLUT-4 and citrate synthase in fast-twitch muscle of voluntary running rats

    NASA Technical Reports Server (NTRS)

    Henriksen, E. J.; Halseth, A. E.

    1995-01-01

    Glucose transporter (GLUT-4) protein, hexokinase, and citrate synthase (proteins involved in oxidative energy production from blood glucose catabolism) increase in response to chronically elevated neuromuscular activity. It is currently unclear whether these proteins increase in a coordinated manner in response to this stimulus. Therefore, voluntary wheel running (WR) was used to chronically overload the fast-twitch rat plantaris muscle and the myocardium, and the early time courses of adaptative responses of GLUT-4 protein and the activities of hexokinase and citrate synthase were characterized and compared. Plantaris hexokinase activity increased 51% after just 1 wk of WR, whereas GLUT-4 and citrate synthase were increased by 51 and 40%, respectively, only after 2 wk of WR. All three variables remained comparably elevated (+50-64%) through 4 wk of WR. Despite the overload of the myocardium with this protocol, no substantial elevations in these variables were observed. These findings are consistent with a coordinated upregulation of GLUT-4 and citrate synthase in the fast-twitch plantaris, but not in the myocardium, in response to this increased neuromuscular activity. Regulation of hexokinase in fast-twitch muscle appears to be uncoupled from regulation of GLUT-4 and citrate synthase, as increases in the former are detectable well before increases in the latter.

  18. The phage-shock-protein response.

    PubMed

    Darwin, Andrew J

    2005-08-01

    The phage-shock-protein (Psp) system responds to extracytoplasmic stress that may reduce the energy status of the cell. It is conserved in many different bacteria and has been linked to several important phenotypes. Escherichia coli psp mutants have defects in maintenance of the proton-motive force, protein export by the sec and tat pathways, survival in stationary phase at alkaline pH, and biofilm formation. Yersinia enterocolitica psp mutants cannot grow when the secretin component of a type III secretion system is mislocalized, and have a severe virulence defect in animals. A Salmonella enterica psp mutation exacerbates some phenotypes of an rpoE null mutant and the psp genes of S. enterica and Shigella flexneri are highly induced during macrophage infection. PspA, the most abundant of the Psp proteins, is required for most of the phenotypes associated with the Psp system. Therefore, PspA is probably an effector that may play a role in maintaining cytoplasmic membrane integrity and/or the proton-motive force. However, PspA is not required for the ability to tolerate secretin mislocalization, which suggests an important physiological role for other Psp proteins. This article summarizes our current understanding of the Psp system: inducing signals, the underlying signal transduction mechanisms, the physiological roles it may play, and a genomic analysis of its conservation.

  19. Exercise training - Blood pressure responses in subjects adapted to microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    1991-01-01

    Conventional endurance exercise training that involves daily workouts of 1-2 hr duration during exposure to microgravity has not proven completely effective in ameliorating postexposure orthostatic hypotension. Single bouts of intense exercise have been shown to increase plasma volume and baroreflex sensitivity in ambulatory subjects through 24 hr postexercise and to reverse decrements in maximal oxygen uptake and syncopal episodes following exposure to simulated microgravity. These physiological adaptations to acute intense exercise were opposite to those observed following exposure to microgravity. These results suggest that the 'exercise training' stimulus used to prevent orthostatic hypotension induced by microgravity may be specific and should be redefined to include single bouts of maximal exercise which may provide an acute effective countermeasure against postflight hypotension.

  20. Differential compartmentalization of Streptococcus pyogenes virulence factors and host protein binding properties as a mechanism for host adaptation.

    PubMed

    Kilsgård, Ola; Karlsson, Christofer; Malmström, Erik; Malmström, Johan

    2016-11-01

    Streptococcus pyogenes is an important human pathogen responsible for substantial morbidity and mortality worldwide. Although S. pyogenes is a strictly human pathogen with no other known animal reservoir, several murine infection models exist to explore different aspects of the bacterial pathogenesis. Inoculating mice with wild-type S. pyogenes strains can result in the generation of new bacterial phenotypes that are hypervirulent compared to the original inoculum. In this study, we used a serial mass spectrometry based proteomics strategy to investigate if these hypervirulent strains have an altered distribution of virulence proteins across the intracellular, surface associated and secreted bacterial compartments and if any change in compartmentalization can alter the protein-protein interaction network between bacteria and host proteins. Quantitative analysis of the S. pyogenes surface and secreted proteomes revealed that animal passaged strains are associated with significantly higher amount of virulence factors on the bacterial surface and in the media. This altered virulence factor compartmentalization results in increased binding of several mouse plasma proteins to the bacterial surface, a trend that was consistent for mouse plasma from several different mouse strains. In general, both the wild-type strain and animal passaged strain were capable of binding high amounts of human plasma proteins. However, compared to the non-passaged strains, the animal passaged strains displayed an increased ability to bind mouse plasma proteins, in particular for M protein binders, indicating that the increased affinity for mouse blood plasma proteins is a consequence of host adaptation of this pathogen to a new host. In conclusion, plotting the total amount of virulence factors against the total amount of plasma proteins associated to the bacterial surface could clearly separate out animal passaged strains from wild type strains indicating a virulence model that could

  1. Evolutionary Dynamics on Protein Bi-stability Landscapes can Potentially Resolve Adaptive Conflicts

    PubMed Central

    Sikosek, Tobias; Bornberg-Bauer, Erich; Chan, Hue Sun

    2012-01-01

    Experimental studies have shown that some proteins exist in two alternative native-state conformations. It has been proposed that such bi-stable proteins can potentially function as evolutionary bridges at the interface between two neutral networks of protein sequences that fold uniquely into the two different native conformations. Under adaptive conflict scenarios, bi-stable proteins may be of particular advantage if they simultaneously provide two beneficial biological functions. However, computational models that simulate protein structure evolution do not yet recognize the importance of bi-stability. Here we use a biophysical model to analyze sequence space to identify bi-stable or multi-stable proteins with two or more equally stable native-state structures. The inclusion of such proteins enhances phenotype connectivity between neutral networks in sequence space. Consideration of the sequence space neighborhood of bridge proteins revealed that bi-stability decreases gradually with each mutation that takes the sequence further away from an exactly bi-stable protein. With relaxed selection pressures, we found that bi-stable proteins in our model are highly successful under simulated adaptive conflict. Inspired by these model predictions, we developed a method to identify real proteins in the PDB with bridge-like properties, and have verified a clear bi-stability gradient for a series of mutants studied by Alexander et al. (Proc Nat Acad Sci USA 2009, 106:21149–21154) that connect two sequences that fold uniquely into two different native structures via a bridge-like intermediate mutant sequence. Based on these findings, new testable predictions for future studies on protein bi-stability and evolution are discussed. PMID:23028272

  2. Converging concepts: adaptive response, preconditioning, and the Yerkes-Dodson Law are manifestations of hormesis.

    PubMed

    Calabrese, Edward J

    2008-01-01

    The adaptive response in toxicology and environmental mutagenesis, preconditioning in biomedicine and the Yerkes-Dodson Law in psychology have dominating research themes with widespread and significant scientific and societal implications. This paper suggests that these apparently independent biological dose-response phenomena are manifestations of the common and more general biphasic dose-response relationship concept called hormesis. These three types of dose-response, as well as the hormesis concept, may represent the same general type of adaptation, which were discovered independently in different biological disciplines, amongst which there has been little communication. This intellectual isolation, due principally to progressively greater disciplinary specialization, resulted in the evolution of different terminologies for dose-response phenomena with strikingly similar quantitative features. This lack of recognition of converging dose-response concepts across disciplines has important implications since it limits the recognition of a common and basic biological concept while minimizing collaborations by investigators in related areas. The paper concludes that the broadly recognized biological adaptive responses, as described by the concepts of adaptive response, preconditioning and the Yerkes-Dodson Law, are special cases of the more general hormesis dose-response concept.

  3. Proteomic analysis of membrane proteins of vero cells: exploration of potential proteins responsible for virus entry.

    PubMed

    Guo, Donghua; Zhu, Qinghe; Zhang, Hong; Sun, Dongbo

    2014-01-01

    Vero cells are highly susceptible to many viruses in humans and animals, and its membrane proteins (MPs) are responsible for virus entry. In our study, the MP proteome of the Vero cells was investigated using a shotgun LC-MS/MS approach. Six hundred twenty-seven proteins, including a total of 1839 peptides, were identified in MP samples of the Vero cells. In 627 proteins, 307 proteins (48.96%) were annotated in terms of biological process of gene ontology (GO) categories; 356 proteins (56.78%) were annotated in terms of molecular function of GO categories; 414 proteins (66.03%) were annotated in terms of cellular components of GO categories. Of 627 identified proteins, seventeen proteins had been revealed to be virus receptor proteins. The resulting protein lists and highlighted proteins may provide valuable information to increase understanding of virus infection of Vero cells.

  4. Protein-surface interactions on stimuli-responsive polymeric biomaterials.

    PubMed

    Cross, Michael C; Toomey, Ryan G; Gallant, Nathan D

    2016-03-04

    Responsive surfaces: a review of the dependence of protein adsorption on the reversible volume phase transition in stimuli-responsive polymers. Specifically addressed are a widely studied subset: thermoresponsive polymers. Findings are also generalizable to other materials which undergo a similarly reversible volume phase transition. As of 2015, over 100,000 articles have been published on stimuli-responsive polymers and many more on protein-biomaterial interactions. Significantly, fewer than 100 of these have focused specifically on protein interactions with stimuli-responsive polymers. These report a clear trend of increased protein adsorption in the collapsed state compared to the swollen state. This control over protein interactions makes stimuli-responsive polymers highly useful in biomedical applications such as wound repair scaffolds, on-demand drug delivery, and antifouling surfaces. Outstanding questions are whether the protein adsorption is reversible with the volume phase transition and whether there is a time-dependence. A clear understanding of protein interactions with stimuli-responsive polymers will advance theoretical models, experimental results, and biomedical applications.

  5. Adaptive response of human melanoma cells to methylglyoxal injury.

    PubMed

    Amicarelli, F; Bucciarelli, T; Poma, A; Aimola, P; Di Ilio, C; Ragnelli, A M; Miranda, M

    1998-03-01

    The effects of methylglyoxal on the growth of a line of human melanoma cells are investigated. Methylglyoxal inhibits cell growth in a dose-dependent manner and causes an increase in glyceraldehyde 3-phosphate dehydrogenase, and glyoxalase 1 and glyoxalase 2 specific activities. The cellular response to increasing concentrations of methylglyoxal in the culture medium is also studied by measuring L-lactate production, reduced-oxidized glutathione levels and apoptotic cell death. Methylglyoxal seems to promote a change of cell population phenotypic repertoire toward a more monomorphic phenotype. In conclusion, methylglyoxal seems to induce an enzymatic cellular response that lowers methylglyoxal levels and selects the most resistant cells.

  6. Response-Adaptive Decision-Theoretic Trial Design: Operating Characteristics and Ethics

    PubMed Central

    Lipsky, Ari M.; Lewis, Roger J.

    2013-01-01

    Adaptive randomization is used in clinical trials to increase statistical efficiency. In addition, some clinicians and researchers believe that using adaptive randomization leads necessarily to more ethical treatment of subjects in a trial. We develop Bayesian, decision-theoretic, clinical trial designs with response-adaptive randomization and a primary goal of estimating treatment effect, and then contrast these designs with designs that also include in their loss function a cost for poor subject outcome. When the loss function did not incorporate a cost for poor subject outcome, the gains in efficiency from response-adaptive randomization were accompanied by ethically concerning subject allocations. Conversely, including a cost for poor subject outcome demonstrated a more acceptable balance between the competing needs in the trial. A subsequent, parallel set of trials designed to control explicitly type I and II error rates showed that much of the improvement achieved through modification of the loss function was essentially negated. Therefore, gains in efficiency from the use of a decision-theoretic, response-adaptive design using adaptive randomization may only be assumed to apply to those goals which are explicitly included in the loss function. Trial goals, including ethical ones, which do not appear in the loss function are ignored and may even be compromised; it is thus inappropriate to assume that all adaptive trials are necessarily more ethical. Controlling type I and II error rates largely negates the benefit of including competing needs in favor of the goal of parameter estimation. PMID:23558674

  7. Variability in the adaptive acid tolerance response phenotype of Salmonella enterica strains.

    PubMed

    Lianou, Alexandra; Nychas, George-John E; Koutsoumanis, Konstantinos P

    2017-04-01

    The objective of this study was the assessment of the stationary-phase, low-pH-inducible acid tolerance response (ATR) of different Salmonella enterica strains. For this purpose, 30 strains of the pathogen were grown in tryptone soy broth in the absence (non-adapted cultures) and presence (1% w/v; acid-adapted cultures) of glucose, and then subjected to 4-h acid challenge trials at pH 3.0. Surviving populations of each strain were determined at 1-h intervals, and the Weibull model was fitted to the derived microbiological data. Extensive variability in the acid stress responses of the tested S. enterica strains was observed, with the total population reductions (log CFU/ml) attained in 4 h of acid challenge ranging from 0.9 to 5.5 and from 0.6 to 7.0 for the non-adapted and acid-adapted cultures, respectively. As demonstrated by the model scale parameter δ and shape parameter p, the effect of acid adaptation on the inactivation curves was strain-specific. Although acid adaptation resulted in enhanced acid survival for the majority of the tested strains, there were strains exhibiting similar or decreased acid resistance compared to their non-adapted counterparts. Moreover, acid adaptation appeared to decrease the strain variability of δ whereas increasing the strain variability of p: the coefficient of variation of δ among the tested strains was 97.2 and 54.9% for the non-adapted and acid-adapted cultures, respectively, while the corresponding values for p were 12.7 and 48.1%. The data of the present study, which is the first one to systematically evaluate the adaptive ATR of multiple S. enterica strains, clearly demonstrate that this phenotype (attempted to be induced by growing the pathogen in the presence of glucose) is strain-dependent.

  8. Kinetic response of a photoperturbed allosteric protein.

    PubMed

    Buchli, Brigitte; Waldauer, Steven A; Walser, Reto; Donten, Mateusz L; Pfister, Rolf; Blöchliger, Nicolas; Steiner, Sandra; Caflisch, Amedeo; Zerbe, Oliver; Hamm, Peter

    2013-07-16

    By covalently linking an azobenzene photoswitch across the binding groove of a PDZ domain, a conformational transition, similar to the one occurring upon ligand binding to the unmodified domain, can be initiated on a picosecond timescale by a laser pulse. The protein structures have been characterized in the two photoswitch states through NMR spectroscopy and the transition between them through ultrafast IR spectroscopy and molecular dynamics simulations. The binding groove opens on a 100-ns timescale in a highly nonexponential manner, and the molecular dynamics simulations suggest that the process is governed by the rearrangement of the water network on the protein surface. We propose this rearrangement of the water network to be another possible mechanism of allostery.

  9. Proteomic analysis of protein expression in Lactobacillus plantarum in response to alkaline stress.

    PubMed

    Lee, KiBeom; Rho, Beom-Seop; Pi, KyungBae; Kim, Ho-Jin; Choi, Yun-Jaie

    2011-04-20

    Lactobacillus plantarum, a probiotic organism that plays an important role in the microbial fermentation of alkaline materials in fermenting foods, faces alkaline stress during the fermentation process. Here, we report the patterns of protein expression in L. plantarum subjected to transient (1h) alkaline stress at pH 7.7, 8.7 or 9.7. Thirty-three alkaline-responsive proteins were identified by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Identification of proteins showing differential expression in response to alkaline stress revealed that the alkaline stress response of L. plantarum is a complex process. Some proteins appear to be induced, others repressed. These proteins could be clustered into nine groups based on their probable functions: energy metabolism, transport system, purine/pyrimidine metabolism, amino acid metabolism, proteolytic activity, transcription-translation, stress-related, general function, and unknown functions. These proteomic analyses are expected to prove useful in understanding the adaptive response of L. plantarum strains to alkaline stress and may facilitate future investigations into the genetic and physiological aspects of this response.

  10. Design of artificial genetic regulatory networks with multiple delayed adaptive responses*

    NASA Astrophysics Data System (ADS)

    Kaluza, Pablo; Inoue, Masayo

    2016-06-01

    Genetic regulatory networks with adaptive responses are widely studied in biology. Usually, models consisting only of a few nodes have been considered. They present one input receptor for activation and one output node where the adaptive response is computed. In this work, we design genetic regulatory networks with many receptors and many output nodes able to produce delayed adaptive responses. This design is performed by using an evolutionary algorithm of mutations and selections that minimizes an error function defined by the adaptive response in signal shapes. We present several examples of network constructions with a predefined required set of adaptive delayed responses. We show that an output node can have different kinds of responses as a function of the activated receptor. Additionally, complex network structures are presented since processing nodes can be involved in several input-output pathways. Supplementary material in the form of one nets file available from the Journal web page at http://dx.doi.org/10.1140/epjb/e2016-70172-9

  11. Vascular heat shock protein expression in response to stress. Endocrine and autonomic regulation of this age-dependent response.

    PubMed Central

    Udelsman, R; Blake, M J; Stagg, C A; Li, D G; Putney, D J; Holbrook, N J

    1993-01-01

    Adaptation to stress requires coordinated interactions between the vascular and endocrine systems. Previously we demonstrated that restraint stress induces the expression of the major heat shock protein, HSP70, in the adrenal cortex of the rat. Here we demonstrate that restraint also induces expression of HSP70 in the vasculature. We further demonstrate that the adrenal and vascular responses are differentially regulated: the adrenal response is adrenocorticotropin dependent, whereas the vascular response is under adrenergic control. In addition, the adrenal response is restricted to members of the HSP70 gene family, whereas in vascular tissue the low molecular weight HSP, HSP27, is also induced by restraint. Further characterization of the vascular response revealed that HSP70 induction occurred in both the thoracic and abdominal aortas as well as in the vena cava. However, no HSP70 induction was apparent in the heart or in a wide variety of other tissues examined. In situ hybridization showed that the vascular expression was localized to the aortic smooth muscle cells with minimal expression in the endothelium. Induction of HSP70 mRNA in both the adrenal cortex and aorta was followed by an elevation in HSP70 protein. Maximum HSP70 protein levels were seen within 3-12 h after restraint, but declined thereafter. Stress induced HSP70 expression was dramatically reduced with age, which may explain, in part, the diminished tolerance to stress seen in elderly individuals. Images PMID:8094399

  12. The plasma membrane-enriched fraction proteome response during adaptation to hydrogen peroxide in Saccharomyces cerevisiae.

    PubMed

    Pedroso, Nuno; Gomes-Alves, Patrícia; Marinho, H Susana; Brito, Verônica B; Boada, Cristina; Antunes, Fernando; Herrero, Enrique; Penque, Deborah; Cyrne, Luísa

    2012-10-01

    In Saccharomyces cerevisiae, adaptation to hydrogen peroxide (H₂O₂) decreases plasma membrane permeability to H₂O₂, changes its lipid composition and reorganizes ergosterol-rich microdomains by a still unknown mechanism. Here we show, by a quantitative analysis of the H₂O₂-induced adaptation effect on the S. cerevisiae plasma membrane-enriched fraction proteome, using two-dimensional gel electrophoresis, that 44 proteins are differentially expressed. Most of these proteins were regulated at a post-transcriptional level. Fourteen of these proteins contain redox-sensitive cysteine residues and nine proteins are associated with lipid and vesicle traffic. In particular, three proteins found in eisosomes and in the eisosome-associated membrane compartment occupied by Can1p were up-regulated (Pil1p, Rfs1p and Pst2p) during adaptation to H₂O₂. Survival studies after exposure to lethal H₂O₂ doses using yeast strains bearing a gene deletion corresponding to proteins associated to lipid and vesicle traffic demonstrated for the first time that down-regulation of Kes1p, Vps4p and Ynl010wp and up-regulation of Atp1 and Atp2 increases resistance to H₂O₂. Moreover, for the pil1Δ strain, H₂O₂ at low levels produces a hormetic effect by increasing proliferation. In conclusion, these data further confirms the plasma membrane as an active cellular site during adaptation to H₂O₂ and shows that proteins involved in lipid and vesicle traffic are important mediators of H₂O₂ adaptation.

  13. Analysis of differential immune responses induced by innate and adaptive immunity following transplantation

    PubMed Central

    He, Hongzhen; Stone, James R; Perkins, David L

    2003-01-01

    The roles of innate and adaptive immunity in allograft rejection remain incompletely understood. Previous studies analysing lymphocyte deficient or syngeneic graft recipients have identified subsets of inflammatory chemokines and cytokines induced by antigen independent mechanisms. In the current study, we analysed a panel of 60 inflammatory parameters including serum cytokines, intragraft chemokines and cytokines, receptors, and cellular markers. Our results confirmed the up-regulation of a subset of markers by innate mechanisms and also identified a subset of parameters up-regulated only in the context of an adaptive response. Thus, we successfully differentiated markers of the innate and adaptive phases of rejection. Current paradigms emphasize that innate signals can promote a subsequent adaptive response. Interestingly, in our studies, expression of the markers induced by innate mechanisms was markedly amplified in the allogeneic, but not syngeneic or lymphocyte deficient, recipients. These results suggest that inflammatory mediators can have functional overlap between the innate and adaptive responses, and that the adaptive component of the rejection process amplifies the innate response by positive feedback regulation. PMID:12757613

  14. Roles and Responsibilities of Adapted Physical Education Teachers in an Urban School District

    ERIC Educational Resources Information Center

    Akuffo, Patrick B.; Hodge, Samuel R.

    2008-01-01

    The purpose of this study is to examine the roles and responsibilities of itinerant adapted physical education (APE) teachers at urban public schools. A second purpose is to determine how they execute their roles and responsibilities. Participants include six women with experience as itinerant APE teachers from the same urban school district. The…

  15. The innate and adaptive immune response to avian influenza virus infections and vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protective immunity against viruses is mediated by the early innate immune responses and later on by the adaptive immune responses. The early innate immunity is designed to contain and limit virus replication in the host, primarily through cytokine and interferon production. Most all cells are cap...

  16. Manganese superoxide dismutase interacts with a large scale of cellular and mitochondrial proteins in low dose radiation-induced adaptive radioprotection

    PubMed Central

    Eldridge, Angela; Fan, Ming; Woloschak, Gayle; Grdina, David J.; Chromy, Brett A.; Li, Jian Jian

    2012-01-01

    Cellular adaptive response to certain low level genotoxic stresses including the exposure to low dose ionizing radiation (LDIR) shows promise as a tool to enhance radioprotection in normal cells but not in tumor cells. Manganese superoxide dismutase (MnSOD), a fundamental mitochondrial antioxidant in mammalian cells plays a key role in LDIR-induced adaptive response. In this study, we aim to elucidate the signaling network associated with the MnSOD-induced radiation protection. A MnSOD-interacting protein profile was established in LDIR-treated human skin cells. Human skin keratinocytes (HK18) were irradiated with a single dose LDIR (10 cGy x-ray) and the cell lysates were immunoprecipitated using α-MnSOD and applied to two different gel-based proteomics followed by mass spectrometry for protein identification. Analysis of the profiles of MnSOD interacting partners before and after LDIR detected different patterns of MnSOD protein-protein interactions in response to LDIR. Interestingly, many of the MnSOD interacting proteins are known to have functions related to mitochondrial regulations on cell metabolism, apoptosis and DNA repair. These results provide the evidence indicating that in addition to the enzymatic action detoxifying superoxide, the antioxidant MnSOD may function as a signaling regulator in stress induced adaptive protection through cell survival pathways. PMID:23000060

  17. Adaptive response studies may help choose astronauts for long-term space travel

    NASA Astrophysics Data System (ADS)

    Mortazavi, S.

    Long-term manned exploratory missions are planned for the next decades. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, requires proper radiation protection planning against the detrimental effects of space radiation. It has been estimated that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding in interplanetary space. Recent findings concerning the induction of adaptive response by neutrons or high levels of external and internal exposures including radon in human cells have opened a new horizon for possible implications of adaptive response in radiation protection and especially in protection against detrimental effects of high levels of radiation during a long-term space journey. Significant adaptive response has been demonstrated in humans after exposure to high levels of natural radiation. It has been shown that in some individuals who fail to show an adaptive response, extraordinary synergism was observed. Interestingly, it was observed that even when the frequency of chromosome aberrations in cells exposed to adapting dose alone or challenge dose alone, were not different than those of other study participants, a severe synergism observed in the cells exposed to challenge dose after an adapting dose. Based on the results obtained in this experiment, due to possible interactions between a chronic low dose and an acute high dose, a common G2 radiosensitivity assay cannot predict radiation risk during a long-term space mission. It can be suggested that the magnitude of adaptive response in lymphocyte samples of potential crew for a deep space mission should be assessed in ground based laboratory studies. Selected space crew who show a high magnitude of adaptive response in ground experiments, will be exposed to adapting higher than normal background radiation doses during mission and they will be considerably more resistant to high doses

  18. The Unfolded Protein Response in Homeostasis and Modulation of Mammalian Immune Cells.

    PubMed

    Martins, Ana Sofia; Alves, Inês; Helguero, Luisa; Domingues, Maria Rosário; Neves, Bruno Miguel

    2016-11-01

    The endoplasmic reticulum (ER) plays important roles in eukaryotic protein folding and lipid biosynthesis. Several exogenous and endogenous cellular sources of stress can perturb ER homeostasis leading to the accumulation of unfolded proteins in the lumen. Unfolded protein accumulation triggers a signal-transduction cascade known as the unfolded protein response (UPR), an adaptive mechanism which aims to protect cells from protein aggregates and to restore ER functions. Further to this protective mechanism, in immune cells, UPR molecular effectors have been shown to participate in a wide range of biological processes such as cell differentiation, survival and immunoglobulin and cytokine production. Recent findings also highlight the involvement of the UPR machinery in the maturational program and antigen presentation capacities of dendritic cells. UPR is therefore a key element in immune system homeostasis with direct implications on both adaptive and innate immune responses. The present review summarizes the knowledge on the emerging roles of UPR signaling cascades in mammalian immune cells as well as the consequences of their dysregulation in relation to the pathogenesis of several diseases.

  19. Adaptive dose finding based on t-statistic for dose-response trials.

    PubMed

    Ivanova, Anastasia; Bolognese, James A; Perevozskaya, Inna

    2008-05-10

    The goals of phase II dose-response studies are to prove that the treatment is effective and to choose the dose for further development. Randomized designs with equal allocation to either a high dose and placebo or to each of several doses and placebo are typically used. However, in trials where response is observed relatively quickly, adaptive designs might offer an advantage over equal allocation. We propose an adaptive design for dose-response trials that concentrates the allocation of subjects in one or more areas of interest, for example, near a minimum clinically important effect level, or near some maximal effect level, and also allows for the possibility to stop the trial early if needed. The proposed adaptive design yields higher power to detect a dose-response relationship, higher power in comparison with placebo, and selects the correct dose more frequently compared with a corresponding randomized design with equal allocation to doses.

  20. gammadelta T cells link innate and adaptive immune responses.

    PubMed

    Holtmeier, Wolfgang; Kabelitz, Dieter

    2005-01-01

    While most T cells use a CD3-associated alpha/beta T cell receptor as antigen recognition structure, a second population of T cells expresses the alternative gamma/delta T cell receptor. gamma/delta T cells are a minor population in the peripheral blood but constitute a major population among intestinal intraepithelial lymphocytes. Most gamma/delta T cells recognize ligands which are fundamentally different from the short peptides that are seen by alpha/beta T cells in the context of MHC class I or class II molecules. Thus, human Vdelta2 T cells recognize small bacterial phosphoantigens, alkylamines and synthetic aminobisphosphonates, whereas Vdelta1 T cells recognize stress-inducible MHC-related molecules MICA/B as well as several other ligands. At the functional level, gamma/delta T cells rapidly produce a variety of cytokines and usually exert potent cytotoxic activity, also towards many tumor cells. In this article, we discuss the role of gamma/delta T cells as a bridge between the innate and the adaptive immune system, based on the interpretation that gamma/delta T cells use their T cell receptor as a pattern recognition receptor. Our increasing understanding of the ligand recognition and activation mechanisms of gamma/delta T cells also opens new perspectives for the development of gamma/delta T cell-based immunotherapies.

  1. Adapt

    NASA Astrophysics Data System (ADS)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  2. Adaptive Control Responses to Behavioral Perturbation Based Upon the Insect

    DTIC Science & Technology

    2006-11-01

    autonomous robot Soc Neuroci Abstr CD ROM 31: :176.110 Harley CM, Predina JD, Ritzmann RE (2006) Responses to incomplete sensory information in cockroach...climbing behavior. Soc Neuroci Abstr CD ROM 32:449.412 Hess D, Buschges A (1999) Role of proprioceptive signals from an insect femur-tibia joint in...Altered joint reflexes in the cockroach may lead to 17 directional changes in leg extension. Soc Neuroci Abstr CD ROM 32:449.411 Pollack AJ

  3. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    PubMed

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

  4. Insights into the adaptive response of the plant-pathogenic oomycete Phytophthora capsici to the fungicide flumorph

    PubMed Central

    Pang, Zhili; Chen, Lei; Mu, Wenjun; Liu, Li; Liu, Xili

    2016-01-01

    Phytophthora capsici is an important oomycete plant pathogen that causes significant losses worldwide. The carboxylic acid amide fungicide flumorph has shown excellent activity against oomycete plant pathogens. Despite its potential, there remains concern that the sexual reproduction of oomycete pathogens, which results in genetic recombination, could result in the rapid development of resistance to flumorph. The current study utilized an iTRAQ (isobaric tags for relative and absolute quantitation) based method to compare differences between the proteome of the parental P. capsici isolate PCAS1 and its sexual progeny S2-838, which exhibits significant resistance to flumorph. A total of 2396 individual proteins were identified, of these, 181 were considered to be associated with the adaptive response of P. capsici to flumorph. The subsequent bioinformatic analysis revealed that the adaptive response of P. capsici to flumorph was complex and regulated by multiple mechanisms, including utilising carbohydrate from the host environment to compensate for the cell wall stress induced by flumorph, a shift in energy generation, decreased amino acids biosynthesis, and elevated levels of proteins associated with the pathogen’s response to stimulus and transmembrane transport. Moreover, the results of the study provided crucial data that could provide the basis for early monitoring of flumorph resistance in field populations of P. capsici. PMID:27050922

  5. Insights into the adaptive response of the plant-pathogenic oomycete Phytophthora capsici to the fungicide flumorph.

    PubMed

    Pang, Zhili; Chen, Lei; Mu, Wenjun; Liu, Li; Liu, Xili

    2016-04-06

    Phytophthora capsici is an important oomycete plant pathogen that causes significant losses worldwide. The carboxylic acid amide fungicide flumorph has shown excellent activity against oomycete plant pathogens. Despite its potential, there remains concern that the sexual reproduction of oomycete pathogens, which results in genetic recombination, could result in the rapid development of resistance to flumorph. The current study utilized an iTRAQ (isobaric tags for relative and absolute quantitation) based method to compare differences between the proteome of the parental P. capsici isolate PCAS1 and its sexual progeny S2-838, which exhibits significant resistance to flumorph. A total of 2396 individual proteins were identified, of these, 181 were considered to be associated with the adaptive response of P. capsici to flumorph. The subsequent bioinformatic analysis revealed that the adaptive response of P. capsici to flumorph was complex and regulated by multiple mechanisms, including utilising carbohydrate from the host environment to compensate for the cell wall stress induced by flumorph, a shift in energy generation, decreased amino acids biosynthesis, and elevated levels of proteins associated with the pathogen's response to stimulus and transmembrane transport. Moreover, the results of the study provided crucial data that could provide the basis for early monitoring of flumorph resistance in field populations of P. capsici.

  6. Gender differences in farmers' responses to climate change adaptation in Yongqiao District, China.

    PubMed

    Jin, Jianjun; Wang, Xiaomin; Gao, Yiwei

    2015-12-15

    This study examines the gender differences in farmers' responses to climate change adaption in Yongqiao District, China. A random sampling technique was used to select 220 household heads, while descriptive statistics and binary logit models were used to analyze the data obtained from the households. We determine that male and female respondents are not significantly different in their knowledge and perceptions of climate change, but there is a gender difference in adopting climate change adaptation measures. Male-headed households are more likely to adopt new technology for water conservation and to increase investment in irrigation infrastructure. The research also indicates that the adaptation decisions of male and female heads are influenced by different sets of factors. The findings of this research help to elucidate the determinants of climate change adaptation decisions for male and female-headed households and the strategic interventions necessary for effective adaptation.

  7. Tissue mechanics govern the rapidly adapting and symmetrical response to touch

    PubMed Central

    Eastwood, Amy L.; Sanzeni, Alessandro; Petzold, Bryan C.; Park, Sung-Jin; Vergassola, Massimo; Pruitt, Beth L.

    2015-01-01

    Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities. PMID:26627717

  8. Fast automated protein NMR data collection and assignment by ADAPT-NMR on Bruker spectrometers

    NASA Astrophysics Data System (ADS)

    Lee, Woonghee; Hu, Kaifeng; Tonelli, Marco; Bahrami, Arash; Neuhardt, Elizabeth; Glass, Karen C.; Markley, John L.

    2013-11-01

    ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a Probabilistic Toolkit in NMR) supports automated NMR data collection and backbone and side chain assignment for [U-13C, U-15N]-labeled proteins. Given the sequence of the protein and data for the orthogonal 2D 1H-15N and 1H-13C planes, the algorithm automatically directs the collection of tilted plane data from a variety of triple-resonance experiments so as to follow an efficient pathway toward the probabilistic assignment of 1H, 13C, and 15N signals to specific atoms in the covalent structure of the protein. Data collection and assignment calculations continue until the addition of new data no longer improves the assignment score. ADAPT-NMR was first implemented on Varian (Agilent) spectrometers [A. Bahrami, M. Tonelli, S.C. Sahu, K.K. Singarapu, H.R. Eghbalnia, J.L. Markley, PLoS One 7 (2012) e33173]. Because of broader interest in the approach, we present here a version of ADAPT-NMR for Bruker spectrometers. We have developed two AU console programs (ADAPT_ORTHO_run and ADAPT_NMR_run) that run under TOPSPIN Versions 3.0 and higher. To illustrate the performance of the algorithm on a Bruker spectrometer, we tested one protein, chlorella ubiquitin (76 amino acid residues), that had been used with the Varian version: the Bruker and Varian versions achieved the same level of assignment completeness (98% in 20 h). As a more rigorous evaluation of the Bruker version, we tested a larger protein, BRPF1 bromodomain (114 amino acid residues), which yielded an automated assignment completeness of 86% in 55 h. Both experiments were carried out on a 500 MHz Bruker AVANCE III spectrometer equipped with a z-gradient 5 mm TCI probe. ADAPT-NMR is available at http://pine.nmrfam.wisc.edu/ADAPT-NMR in the form of pulse programs, the two AU programs, and instructions for installation and use.

  9. Fast automated protein NMR data collection and assignment by ADAPT-NMR on Bruker spectrometers.

    PubMed

    Lee, Woonghee; Hu, Kaifeng; Tonelli, Marco; Bahrami, Arash; Neuhardt, Elizabeth; Glass, Karen C; Markley, John L

    2013-11-01

    ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a Probabilistic Toolkit in NMR) supports automated NMR data collection and backbone and side chain assignment for [U-(13)C, U-(15)N]-labeled proteins. Given the sequence of the protein and data for the orthogonal 2D (1)H-(15)N and (1)H-(13)C planes, the algorithm automatically directs the collection of tilted plane data from a variety of triple-resonance experiments so as to follow an efficient pathway toward the probabilistic assignment of (1)H, (13)C, and (15)N signals to specific atoms in the covalent structure of the protein. Data collection and assignment calculations continue until the addition of new data no longer improves the assignment score. ADAPT-NMR was first implemented on Varian (Agilent) spectrometers [A. Bahrami, M. Tonelli, S.C. Sahu, K.K. Singarapu, H.R. Eghbalnia, J.L. Markley, PLoS One 7 (2012) e33173]. Because of broader interest in the approach, we present here a version of ADAPT-NMR for Bruker spectrometers. We have developed two AU console programs (ADAPT_ORTHO_run and ADAPT_NMR_run) that run under TOPSPIN Versions 3.0 and higher. To illustrate the performance of the algorithm on a Bruker spectrometer, we tested one protein, chlorella ubiquitin (76 amino acid residues), that had been used with the Varian version: the Bruker and Varian versions achieved the same level of assignment completeness (98% in 20 h). As a more rigorous evaluation of the Bruker version, we tested a larger protein, BRPF1 bromodomain (114 amino acid residues), which yielded an automated assignment completeness of 86% in 55 h. Both experiments were carried out on a 500 MHz Bruker AVANCE III spectrometer equipped with a z-gradient 5 mm TCI probe. ADAPT-NMR is available at http://pine.nmrfam.wisc.edu/ADAPT-NMR in the form of pulse programs, the two AU programs, and instructions for installation and use.

  10. The adaptive evolution of plasticity: phytochrome-mediated shade avoidance responses.

    PubMed

    Schmitt, Johanna; Stinchcombe, John R; Heschel, M Shane; Huber, Heidrun

    2003-07-01

    Many plants display a characteristic suite of developmental "shade avoidance" responses, such as stem elongation and accelerated reproduction, to the low ratio of red to far-red wavelengths (R:FR) reflected or transmitted from green vegetation. This R:FR cue of crowding and vegetation shade is perceived by the phytochrome family of photoreceptors. Phytochrome-mediated responses provide an ideal system for investigating the adaptive evolution of phenotypic plasticity in natural environments. The molecular and developmental mechanisms underlying shade avoidance responses are well studied, and testable ecological hypotheses exist for their adaptive significance. Experimental manipulation of phenotypes demonstrates that shade avoidance responses may be adaptive, resulting in phenotypes with high relative fitness in the environments that induce those phenotypes. The adaptive value of shade avoidance depends upon the competitive environment, resource availability, and the reliability of the R:FR cue for predicting the selective environment experienced by an induced phenotype. Comparative studies and a reciprocal transplant experiment with Impatiens capensis provide evidence of adaptive divergence in shade avoidance responses between woodland and clearing habitats, which may result from population differences in the frequency of selection on shade avoidance traits, as well as differences in the reliability of the R:FR cue. Recent rapid progress in elucidating phytochrome signaling pathways in the genetic model Arabidopsis thaliana and other species now provides the opportunity for studying how selection on shade avoidance traits in natural environments acts upon the molecular mechanisms underlying natural phenotypic variation.

  11. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

    PubMed Central

    Yang, Ying; Ju, Jieyang; Deng, Min; Wang, Jing; Liu, Hui; Xiong, Li; Zhang, Junjian

    2017-01-01

    Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs), were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit. PMID:28106731

  12. Intra-plastid protein trafficking: how plant cells adapted prokaryotic mechanisms to the eukaryotic condition.

    PubMed

    Celedon, Jose M; Cline, Kenneth

    2013-02-01

    Protein trafficking and localization in plastids involve a complex interplay between ancient (prokaryotic) and novel (eukaryotic) translocases and targeting machineries. During evolution, ancient systems acquired new functions and novel translocation machineries were developed to facilitate the correct localization of nuclear encoded proteins targeted to the chloroplast. Because of its post-translational nature, targeting and integration of membrane proteins posed the biggest challenge to the organelle to avoid aggregation in the aqueous compartments. Soluble proteins faced a different kind of problem since some had to be transported across three membranes to reach their destination. Early studies suggested that chloroplasts addressed these issues by adapting ancient-prokaryotic machineries and integrating them with novel-eukaryotic systems, a process called 'conservative sorting'. In the last decade, detailed biochemical, genetic, and structural studies have unraveled the mechanisms of protein targeting and localization in chloroplasts, suggesting a highly integrated scheme where ancient and novel systems collaborate at different stages of the process. In this review we focus on the differences and similarities between chloroplast ancestral translocases and their prokaryotic relatives to highlight known modifications that adapted them to the eukaryotic situation. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids.

  13. Understanding the adaptive response in vertebrates: the phenomenon of ease and ease response during post-stress acclimation.

    PubMed

    Subhash Peter, M C

    2013-01-15

    Vertebrates have evolved mechanisms to perceive stressors that arise either from their body or from the environment. Consequently, a state of stress and stress response occur in fish which is characterized by a disturbed physiological homeostasis. The pattern of stress response becomes complex as a result of neuroendocrine involvement and shows varied magnitudes in fishes depending on the nature and the severity of stressors. The integrated and compensatory physiological modifications in fishes during their early phase of adaptive response favor them to accommodate the imposed stressor through the process of stress acclimation. In contrast, with the direction of neuroendocrine signals, a phase of recovery often called post-stress acclimation occurs if the animal gets away from the stressor exposure. During this late phase of adaptive response, physiological modifications operate in favor of the animal that reduces the magnitude of stress response and finally to a phase of normality as animals possess the urge to correct its disrupted homeostasis. The phenomenon of ease and its response thus reduces the allostatic load, resets the homeostatic state through physiologic processes and corrects the stress-induced homeostatic disturbance with the aid of neuroendocrine signals. Ample evidences are now available to support this novel concept of ease and ease response where mitigation of the intensity of stress response occurs physiologically. Treatment of fish with melatonin or serotonin precursor tryptophan can modify the magnitude of stress response as evident in the pattern of tested physiological indices. In addition to cortisol, thyroid hormone as a major stress modifier hormone is involved in the regulation of ease response in fish probably due to the mechanisms involving inter-hormonal interference. Understanding the mechanisms of adaptive responses in vertebrates thus warranties more studies on the physiology of ease and its response.

  14. Quantifying Rates of Evolutionary Adaptation in Response to Ocean Acidification

    PubMed Central

    Sunday, Jennifer M.; Crim, Ryan N.; Harley, Christopher D. G.; Hart, Michael W.

    2011-01-01

    The global acidification of the earth's oceans is predicted to impact biodiversity via physiological effects impacting growth, survival, reproduction, and immunology, leading to changes in species abundances and global distributions. However, the degree to which these changes will play out critically depends on the evolutionary rate at which populations will respond to natural selection imposed by ocean acidification, which remains largely unquantified. Here we measure the potential for an evolutionary response to ocean acidification in larval development rate in two coastal invertebrates using a full-factorial breeding design. We show that the sea urchin species Strongylocentrotus franciscanus has vastly greater levels of phenotypic and genetic variation for larval size in future CO2 conditions compared to the mussel species Mytilus trossulus. Using these measures we demonstrate that S. franciscanus may have faster evolutionary responses within 50 years of the onset of predicted year-2100 CO2 conditions despite having lower population turnover rates. Our comparisons suggest that information on genetic variation, phenotypic variation, and key demographic parameters, may lend valuable insight into relative evolutionary potentials across a large number of species. PMID:21857962

  15. The negatively charged regions of lactoferrin binding protein B, an adaptation against anti-microbial peptides.

    PubMed

    Morgenthau, Ari; Beddek, Amanda; Schryvers, Anthony B

    2014-01-01

    Lactoferrin binding protein B (LbpB) is a bi-lobed membrane bound lipoprotein that is part of the lactoferrin receptor complex in a variety of Gram-negative pathogens. Despite high sequence diversity among LbpBs from various strains and species, a cluster of negatively charged amino acids is invariably present in the protein's C-terminal lobe in all species except Moraxella bovis. The function of LbpB in iron acquisition has yet to be experimentally demonstrated, whereas in vitro studies have shown that LbpB confers protection against lactoferricin, a short cationic antimicrobial peptide released from the N- terminus of lactoferrin. In this study we demonstrate that the negatively charged regions can be removed from the Neisseria meningitidis LbpB without compromising stability, and this results in the inability of LbpB to protect against the bactericidal effects of lactoferricin. The release of LbpB from the cell surface by the autotransporter NalP reduces the protection against lactoferricin in the in vitro killing assay, attributed to removal of LbpB during washing steps, but is unlikely to have a similar impact in vivo. The protective effect of the negatively charged polysaccharide capsule in the killing assay was less than the protection conferred by LbpB, suggesting that LbpB plays a major role in protection against cationic antimicrobial peptides in vivo. The selective release of LbpB by NalP has been proposed to be a mechanism for evading the adaptive immune response, by reducing the antibody binding to the cell surface, but may also provide insights into the primary function of LbpB in vivo. Although TbpB and LbpB have been shown to be major targets of the human immune response, the selective release of LbpB suggests that unlike TbpB, LbpB may not be essential for iron acquisition, but important for protection against cationic antimicrobial peptides.

  16. Stimuli-Responsive Nanomaterials for Therapeutic Protein Delivery

    PubMed Central

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-01-01

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. PMID:25151983

  17. Proximal Tubule Glutamine Synthetase Expression is Necessary for the Normal Response to Dietary Protein Restriction.

    PubMed

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Verlander, Jill W; Weiner, I David

    2017-03-22

    Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The current study's purpose was to determine proximal tubule GS's role in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule glutamine synthetase expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

  18. Life at the border: Adaptation of proteins to anisotropic membrane environment

    PubMed Central

    Pogozheva, Irina D; Mosberg, Henry I; Lomize, Andrei L

    2014-01-01

    This review discusses main features of transmembrane (TM) proteins which distinguish them from water-soluble proteins and allow their adaptation to the anisotropic membrane environment. We overview the structural limitations on membrane protein architecture, spatial arrangement of proteins in membranes and their intrinsic hydrophobic thickness, co-translational and post-translational folding and insertion into lipid bilayers, topogenesis, high propensity to form oligomers, and large-scale conformational transitions during membrane insertion and transport function. Special attention is paid to the polarity of TM protein surfaces described by profiles of dipolarity/polarizability and hydrogen-bonding capacity parameters that match polarity of the lipid environment. Analysis of distributions of Trp resides on surfaces of TM proteins from different biological membranes indicates that interfacial membrane regions with preferential accumulation of Trp indole rings correspond to the outer part of the lipid acyl chain region—between double bonds and carbonyl groups of lipids. These “midpolar” regions are not always symmetric in proteins from natural membranes. We also examined the hydrophobic effect that drives insertion of proteins into lipid bilayer and different free energy contributions to TM protein stability, including attractive van der Waals forces and hydrogen bonds, side-chain conformational entropy, the hydrophobic mismatch, membrane deformations, and specific protein–lipid binding. PMID:24947665

  19. Effects of local adaptation and interspecific competition on species' responses to climate change.

    PubMed

    Bocedi, Greta; Atkins, Katherine E; Liao, Jishan; Henry, Roslyn C; Travis, Justin M J; Hellmann, Jessica J

    2013-09-01

    Local adaptation and species interactions have been shown to affect geographic ranges; therefore, we need models of climate impact that include both factors. To identify possible dynamics of species when including these factors, we ran simulations of two competing species using an individual-based, coupled map-lattice model using a linear climatic gradient that varies across latitude and is warmed over time. Reproductive success is governed by an individual's adaptation to local climate as well as its location relative to global constraints. In exploratory experiments varying the strength of adaptation and competition, competition reduces genetic diversity and slows range change, although the two species can coexist in the absence of climate change and shift in the absence of competitors. We also found that one species can drive the other to extinction, sometimes long after climate change ends. Weak selection on local adaptation and poor dispersal ability also caused surfing of cooler-adapted phenotypes from the expanding margin backwards, causing loss of warmer-adapted phenotypes. Finally, geographic ranges can become disjointed, losing centrally-adapted genotypes. These initial results suggest that the interplay between local adaptation and interspecific competition can significantly influence species' responses to climate change, in a way that demands future research.

  20. The Adaptive Response, Genetic Haplo-Insufficiency and Genomic Instability

    SciTech Connect

    Geard, Charles R.

    2014-12-12

    The linear no-threshold (LNT) hypothesis is the driving force in the establishment of radiation protection standards. However, the scientific basis for linearity has been brought into question, particularly due to the concerns about induced radiation resistance as it pertains to oxidative stress. Specifically, we investigated the observation that tumor hypoxia is associated with malignant progression, increased metastases, chemo- and radioresistance and poor prognosis. Experiments were conducted with non-malignant 3T3/NIH cells and normal human lung fibroblasts (NHLF) that were subjected to γ-irradiation under the levels of oxygen resembling those in growing tumors, and related our data to the concentrations of dissolved oxygen (DO), which is a better indicator of the amounts of residual oxygen inside the cells cultured in the hypoxic or anoxic atmosphere. We found that at DO levels about 0.5 mg/L cells subjected to both short-term (17 hours) and prolonged (48-72 hours) hypoxia continued to proliferate, and that apoptotic events were decreased at the early hours of hypoxic treatment. We showed that the short-term hypoxia up-regulated p53-binding protein 1 (53BP1) and resulted in facilitated 53BP1 nuclear foci formation and disappearance, thus indicating the higher efficiency of DNA double strand breaks repair processes. The latter was confirmed by the lower micronuclei incidence in irradiated hypoxic cells.

  1. Adaptive liquid microlenses activated by stimuli-responsive hydrogels

    NASA Astrophysics Data System (ADS)

    Dong, Liang; Agarwal, Abhishek K.; Beebe, David J.; Jiang, Hongrui

    2006-08-01

    Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths, or use external control to adjust the microlens focal length. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape-and hence focal length-of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably, we can use pinned liquid-liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -∞ to +∞ (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies.

  2. An adaptive response of Enterobacter aerogenes to imipenem: regulation of porin balance in clinical isolates.

    PubMed

    Lavigne, Jean-Philippe; Sotto, Albert; Nicolas-Chanoine, Marie-Hélène; Bouziges, Nicole; Pagès, Jean-Marie; Davin-Regli, Anne

    2013-02-01

    Imipenem (IPM) is a carbapenem antibiotic frequently used in severe hospital infections. Several reports have mentioned the emergence of resistant isolates exhibiting membrane modifications. A study was conducted between September 2005 and August 2007 to survey infections due to Enterobacter aerogenes in patients hospitalised in a French university hospital. Resistant E. aerogenes clinical isolates obtained from patients treated with IPM and collected during the 3 months following initiation of treatment were phenotypically and molecularly characterised for β-lactamases, efflux pumps activity and outer membrane proteins. Among the 339 patients infected with E. aerogenes during the study period, 41 isolates (12.1%) were resistant to extended-spectrum cephalosporins and 17 patients (5.0%) were treated with IPM. The isolates from these 17 patients presented TEM-24 and basal efflux expression. Following IPM treatment, an IPM-intermediate-susceptible (IPM-I) isolate emerged in 11 patients and an IPM-resistant (IPM-R) isolate in 6 patients. A change in the porin balance (Omp35/Omp36) was observed in IPM-I isolates exhibiting ertapenem resistance. Finally, a porin deficiency (Omp35 and Omp36 absence) was detected in IPM-R isolates associated with efflux pump expression. This study indicates that the alteration in porin expression, including the shift of porin expression and lack of porins, contribute to the E. aerogenes adaptive response to IPM treatment.

  3. Adaptive response in animals exposed to non-ionizing radiofrequency fields: some underlying mechanisms.

    PubMed

    Cao, Yi; Tong, Jian

    2014-04-22

    During the last few years, our research group has been investigating the phenomenon of adaptive response in animals exposed to non-ionizing radiofrequency fields. The results from several separate studies indicated a significant increase in survival, decreases in genetic damage as well as oxidative damage and, alterations in several cellular processes in mice pre-exposed to radiofrequency fields and subsequently subjected to sub-lethal or lethal doses of γ-radiation or injected with bleomycin, a radiomimetic chemical mutagen. These observations indicated the induction of adaptive response providing the animals the ability to resist subsequent damage. Similar studies conducted by independent researchers in mice and rats have supported our observation on increased survival. In this paper, we have presented a brief review of all of our own and other independent investigations on radiofrequency fields-induced adaptive response and some underlying mechanisms discussed.

  4. Concluding remarks: nutritional strategies to support the adaptive response to prolonged exercise training.

    PubMed

    van Loon, Luc J C; Tipton, Kevin D

    2013-01-01

    Nutrition plays a key role in allowing the numerous training hours to be translated into useful adaptive responses of various tissues in the individual athlete. Research over the last decade has shown many examples of the impact of dietary interventions to modulate the skeletal muscle adaptive response to prolonged exercise training. Proper nutritional coaching should be applied throughout both training and competition, each with their specific requirements regarding nutrient provision. Such dietary support will improve exercise training efficiency and, as such, further increase performance capacity. Here, we provide an overview on the properties of various nutritional interventions that may be useful to support the adaptive response to exercise training and competition and, as such, to augment exercise training efficiency.

  5. Innate and adaptive antifungal immune responses: partners on an equal footing.

    PubMed

    Hamad, Mawieh

    2012-05-01

    Adaptive immunity has long been regarded as the major player in protection against most fungal infections. Mounting evidence suggest however, that both innate and adaptive responses intricately collaborate to produce effective antifungal protection. Dendritic cells (DCs) play an important role in initiating and orchestrating antifungal immunity; neutrophils, macrophages and other phagocytes also participate in recognising and eliminating fungal pathogens. Adaptive immunity provides a wide range of effector and regulatory responses against fungal infections. Th1 responses protect against most forms of mycoses but they associate with significant inflammation and limited pathogen persistence. By contrast, Th2 responses enhance persistence of and tolerance to fungal infections thus permitting the generation of long-lasting immunological memory. Although the role of Th17 cytokines in fungal immunity is not fully understood, they can enhance proinflammatory or anti-inflammatory responses or play a regulatory role in fungal immunity all depending on the pathogen, site/phase of infection and host immunostatus. T regulatory cells balance the activities of various Th cell subsets thereby permitting inflammation and protection on the one hand and allowing for tolerance and memory on the other. Here, recent developments in fungal immunity research are reviewed as means of tracing the emergence of a refined paradigm where innate and adaptive responses are viewed in the same light.

  6. Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change.

    PubMed

    Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

    2014-01-01

    Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data.

  7. Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change

    PubMed Central

    Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

    2014-01-01

    Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data. PMID:24454550

  8. Rewiring Multidomain Protein Switches: Transforming a Fluorescent Zn(2+) Sensor into a Light-Responsive Zn(2+) Binding Protein.

    PubMed

    Aper, Stijn J A; Merkx, Maarten

    2016-07-15

    Protein-based sensors and switches provide attractive tools for the real-time monitoring and control of molecular processes in complex biological environments. Fluorescent sensor proteins have been developed for a wide variety of small molecules, but the construction of genetically encoded light-responsive ligand binding proteins remains mostly unexplored. Here we present a generic approach to reengineer a previously developed FRET-based Zn(2+) sensor into a light-activatable Zn(2+) binding protein using a design strategy based on mutually exclusive domain interactions. These so-called VividZn proteins consist of two light-responsive Vivid domains that homodimerize upon illumination with blue light, thus preventing the binding of Zn(2+) between two Zn(2+) binding domains, Atox1 and WD4. Following optimization of the linker between WD4 and the N-terminus of one of the Vivid domains, VividZn variants were obtained that show a 9- to 55-fold decrease in Zn(2+) affinity upon illumination, which is fully reversible following dark adaptation. The Zn(2+) affinities of the switch could be rationally tuned between 1 pM and 2 nM by systematic variation of linker length and mutation of one of the Zn(2+) binding residues. Similarly, introduction of mutations in the Vivid domains allowed tuning of the switching kinetics between 10 min and 7 h. Low expression levels in mammalian cells precluded the demonstration of light-induced perturbation of cytosolic Zn(2+) levels. Nonetheless, our results firmly establish the use of intramolecular Vivid dimerization as an attractive light-sensitive input module to rationally engineer light-responsive protein switches based on mutually exclusive domain interactions.

  9. Increased anterior cingulate cortex response precedes behavioural adaptation in anorexia nervosa

    PubMed Central

    Geisler, Daniel; Ritschel, Franziska; King, Joseph A.; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N.; Ehrlich, Stefan

    2017-01-01

    Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN. PMID:28198813

  10. Increased anterior cingulate cortex response precedes behavioural adaptation in anorexia nervosa.

    PubMed

    Geisler, Daniel; Ritschel, Franziska; King, Joseph A; Bernardoni, Fabio; Seidel, Maria; Boehm, Ilka; Runge, Franziska; Goschke, Thomas; Roessner, Veit; Smolka, Michael N; Ehrlich, Stefan

    2017-02-13

    Patients with anorexia nervosa (AN) are characterised by increased self-control, cognitive rigidity and impairments in set-shifting, but the underlying neural mechanisms are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of behavioural adaptation to changes in reward contingencies in young acutely ill AN patients. Thirty-six adolescent/young adult, non-chronic female AN patients and 36 age-matched healthy females completed a well-established probabilistic reversal learning task during fMRI. We analysed hemodynamic responses in empirically-defined regions of interest during positive feedback and negative feedback not followed/followed by behavioural adaptation and conducted functional connectivity analyses. Although overall task performance was comparable between groups, AN showed increased shifting after receiving negative feedback (lose-shift behaviour) and altered dorsal anterior cingulate cortex (dACC) responses as a function of feedback. Specifically, patients had increased dACC responses (which correlated with perfectionism) and task-related coupling with amygdala preceding behavioural adaption. Given the generally preserved task performance in young AN, elevated dACC responses specifically during behavioural adaption is suggestive of increased monitoring for the need to adjust performance strategies. Higher dACC-amygdala coupling and increased adaptation after negative feedback underlines this interpretation and could be related to intolerance of uncertainty which has been suggested for AN.

  11. Transcription Factor Functional Protein-Protein Interactions in Plant Defense Responses

    PubMed Central

    Alves, Murilo S.; Dadalto, Silvana P.; Gonçalves, Amanda B.; de Souza, Gilza B.; Barros, Vanessa A.; Fietto, Luciano G.

    2014-01-01

    Responses to biotic stress in plants lead to dramatic reprogramming of gene expression, favoring stress responses at the expense of normal cellular functions. Transcription factors are master regulators of gene expression at the transcriptional level, and controlling the activity of these factors alters the transcriptome of the plant, leading to metabolic and phenotypic changes in response to stress. The functional analysis of interactions between transcription factors and other proteins is very important for elucidating the role of these transcriptional regulators in different signaling cascades. In this review, we present an overview of protein-protein interactions for the six major families of transcription factors involved in plant defense: basic leucine zipper containing domain proteins (bZIP), amino-acid sequence WRKYGQK (WRKY), myelocytomatosis related proteins (MYC), myeloblastosis related proteins (MYB), APETALA2/ ETHYLENE-RESPONSIVE ELEMENT BINDING FACTORS (AP2/EREBP) and no apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), and cup-shaped cotyledon (CUC) (NAC). We describe the interaction partners of these transcription factors as molecular responses during pathogen attack and the key components of signal transduction pathways that take place during plant defense responses. These interactions determine the activation or repression of response pathways and are crucial to understanding the regulatory networks that modulate plant defense responses. PMID:28250372

  12. Live imaging using adaptive optics with fluorescent protein guide-stars

    PubMed Central

    Tao, Xiaodong; Crest, Justin; Kotadia, Shaila; Azucena, Oscar; Chen, Diana C.; Sullivan, William; Kubby, Joel

    2012-01-01

    Spatially and temporally dependent optical aberrations induced by the inhomogeneous refractive index of live samples limit the resolution of live dynamic imaging. We introduce an adaptive optical microscope with a direct wavefront sensing method using a Shack-Hartmann wavefront sensor and fluorescent protein guide-stars for live imaging. The results of imaging Drosophila embryos demonstrate its ability to correct aberrations and achieve near diffraction limited images of medial sections of large Drosophila embryos. GFP-polo labeled centrosomes can be observed clearly after correction but cannot be observed before correction. Four dimensional time lapse images are achieved with the correction of dynamic aberrations. These studies also demonstrate that the GFP-tagged centrosome proteins, Polo and Cnn, serve as excellent biological guide-stars for adaptive optics based microscopy. PMID:22772285

  13. Osteopontin Expression in Acute Immune Response Mediates Hippocampal Synaptogenesis and Adaptive Outcome Following Cortical Brain Injury

    PubMed Central

    Chan, Julie L.; Reeves, Thomas M.; Phillips, Linda L.

    2014-01-01

    Traumatic brain injury (TBI) produces axotomy, deafferentation and reactive synaptogenesis. Inflammation influences synaptic repair, and the novel brain cytokine osteopontin (OPN) has potential to support axon regeneration through exposure of its integrin receptor binding sites. This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity. Over the first week postinjury, hippocampal OPN protein and mRNA were assayed and histology performed. At 1–2d, OPN protein increased up to 51 fold, and was localized within activated, mobilized glia. OPN transcript also increased over 50 fold, predominantly within reactive microglia. OPN fragments known to be derived from MMP proteolysis were elevated at 1d, consistent with prior reports of UEC glial activation and enzyme production. Postinjury minocycline immunosuppression attenuated MMP-9 gelatinase activity, which was correlated with reduction of neutrophil gelatinase-associated lipocalin (LCN2) expression, and reduced OPN fragment generation. The antibiotic also attenuated removal of synapsin-1 positive axons from the deafferented zone. OPN KO mice subjected to UEC had similar reduction of hippocampal MMP-9 activity, as well as lower synapsin-1 breakdown over the deafferented zone. MAP1B and N-cadherin, surrogates of cytoarchitecture and synaptic adhesion, were not affected. OPN KO mice with UEC exhibited time dependent cognitive deficits during the synaptogenic phase of recovery. This study demonstrates that OPN can mediate immune response during TBI synaptic repair, positively influencing synapse reorganization and functional recovery. PMID:25151457

  14. Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli.

    PubMed

    Yosef, Ido; Goren, Moran G; Qimron, Udi

    2012-07-01

    The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR/Cas) constitute a recently identified prokaryotic defense mechanism against invading nucleic acids. Activity of the CRISPR/Cas system comprises of three steps: (i) insertion of alien DNA sequences into the CRISPR array to prevent future attacks, in a process called 'adaptation', (ii) expression of the relevant proteins, as well as expression and processing of the array, followed by (iii) RNA-mediated interference with the alien nucleic acid. Here we describe a robust assay in Escherichia coli to explore the hitherto least-studied process, adaptation. We identify essential genes and DNA elements in the leader sequence and in the array which are essential for the adaptation step. We also provide mechanistic insights on the insertion of the repeat-spacer unit by showing that the first repeat serves as the template for the newly inserted repeat. Taken together, our results elucidate fundamental steps in the adaptation process of the CRISPR/Cas system.

  15. Adaptability of protein structures to enable functional interactions and evolutionary implications.

    PubMed

    Haliloglu, Turkan; Bahar, Ivet

    2015-12-01

    Several studies in recent years have drawn attention to the ability of proteins to adapt to intermolecular interactions by conformational changes along structure-encoded collective modes of motions. These so-called soft modes, primarily driven by entropic effects, facilitate, if not enable, functional interactions. They represent excursions on the conformational space along principal low-ascent directions/paths away from the original free energy minimum, and they are accessible to the protein even before protein-protein/ligand interactions. An emerging concept from these studies is the evolution of structures or modular domains to favor such modes of motion that will be recruited or integrated for enabling functional interactions. Structural dynamics, including the allosteric switches in conformation that are often stabilized upon formation of complexes and multimeric assemblies, emerge as key properties that are evolutionarily maintained to accomplish biological activities, consistent with the paradigm sequence→structure→dynamics→function where 'dynamics' bridges structure and function.

  16. Immune adjuvants in early life: targeting the innate immune system to overcome impaired adaptive response.

    PubMed

    de Brito, Cyro Alves; Goldoni, Adriana Letícia; Sato, Maria Notomi

    2009-09-01

    The neonatal phase is a transitory period characterized by an absence of memory cells, favoring a slow adaptive response prone to tolerance effects and the development of Th2-type responses. However, when appropriately stimulated, neonates may achieve an immune response comparable with adult counterparts. One strategy to stimulate the immunological response of neonates or children in early infancy has been to explore natural or synthetic ligands of cell receptors to stimulate innate immunity. The use of adjuvants for activating different cell receptors may be the key to enhancing neonatal adaptive immunity. This review highlights recent advances in the emerging field of molecular adjuvants of innate immune response and their implications for the development of immunotherapies, with particular focus on the neonatal period.

  17. Extracellular proteins of Cryptococcus neoformans and host antibody response.

    PubMed Central

    Chen, L C; Pirofski, L A; Casadevall, A

    1997-01-01

    Proteins secreted by the fungal pathogen Cryptococcus neoformans may be involved in invasion and could be useful in vaccine design. Despite the medical importance of this fungus, little is known about its extracellular proteins or the immune response to these antigens. To study C. neoformans extracellular proteins, 12 strains were metabolically radiolabeled and protein supernatants were analyzed. Both strain- and growth condition-dependent differences were observed. Enzymatic assays of filtered culture supernatants revealed butyrate esterase and caprylate esterase lipase activity for 11 of 12 strains, as well as acid phosphatase, naphthol-AS-BI-phosphohydrolase, and beta-glucosidase activities in some strains. Serum from infected rodents immunoprecipitated several secreted proteins, consistent with in vivo expression and development of an antibody response. For strain 24067, two immunodominant species, of approximately 75 and 30 kDa, were recognized. The relative intensity of the autoradiographic bands depended on the route of infection for both rats and mice. In summary, our results indicate that (i) there are multiple proteins in C. neoformans culture supernatants, (ii) there are strain differences in supernatant protein profiles, (iii) there are differences in supernatant protein profile depending on the growth conditions, (iv) there are several new extracellular and/or cell-associated enzymatic activities, and (v) antibodies to several supernatant proteins are made in the course of infection. PMID:9199426

  18. Physical and molecular bases of protein thermal stability and cold adaptation.

    PubMed

    Pucci, Fabrizio; Rooman, Marianne

    2017-02-01

    The molecular bases of thermal and cold stability and adaptation, which allow proteins to remain folded and functional in the temperature ranges in which their host organisms live and grow, are still only partially elucidated. Indeed, both experimental and computational studies fail to yield a fully precise and global physical picture, essentially because all effects are context-dependent and thus quite intricate to unravel. We present a snapshot of the current state of knowledge of this highly complex and challenging issue, whose resolution would enable large-scale rational protein design.

  19. Evolution of taxis responses in virtual bacteria: non-adaptive dynamics.

    PubMed

    Goldstein, Richard A; Soyer, Orkun S

    2008-05-23

    Bacteria are able to sense and respond to a variety of external stimuli, with responses that vary from stimuli to stimuli and from species to species. The best-understood is chemotaxis in the model organism Escherichia coli, where the dynamics and the structure of the underlying pathway are well characterised. It is not clear, however, how well this detailed knowledge applies to mechanisms mediating responses to other stimuli or to pathways in other species. Furthermore, there is increasing experimental evidence that bacteria integrate responses from different stimuli to generate a coherent taxis response. We currently lack a full understanding of the different pathway structures and dynamics and how this integration is achieved. In order to explore different pathway structures and dynamics that can underlie taxis responses in bacteria, we perform a computational simulation of the evolution of taxis. This approach starts with a population of virtual bacteria that move in a virtual environment based on the dynamics of the simple biochemical pathways they harbour. As mutations lead to changes in pathway structure and dynamics, bacteria better able to localise with favourable conditions gain a selective advantage. We find that a certain dynamics evolves consistently under different model assumptions and environments. These dynamics, which we call non-adaptive dynamics, directly couple tumbling probability of the cell to increasing stimuli. Dynamics that are adaptive under a wide range of conditions, as seen in the chemotaxis pathway of E. coli, do not evolve in these evolutionary simulations. However, we find that stimulus scarcity and fluctuations during evolution results in complex pathway dynamics that result both in adaptive and non-adaptive dynamics depending on basal stimuli levels. Further analyses of evolved pathway structures show that effective taxis dynamics can be mediated with as few as two components. The non-adaptive dynamics mediating taxis responses

  20. Integrated Physiological, Proteomic, and Metabolomic Analysis of Ultra Violet (UV) Stress Responses and Adaptation Mechanisms in Pinus radiata.

    PubMed

    Pascual, Jesús; Cañal, María Jesús; Escandón, Mónica; Meijón, Mónica; Weckwerth, Wolfram; Valledor, Luis

    2017-03-01

    Globally expected changes in environmental conditions, especially the increase of UV irradiation, necessitate extending our knowledge of the mechanisms mediating tree species adaptation to this stress. This is crucial for designing new strategies to maintain future forest productivity. Studies focused on environmentally realistic dosages of UV irradiation in forest species are scarce. Pinus spp. are commercially relevant trees and not much is known about their adaptation to UV. In this work, UV treatment and recovery of Pinus radiata plants with dosages mimicking future scenarios, based on current models of UV radiation, were performed in a time-dependent manner. The combined metabolome and proteome analysis were complemented with measurements of + physiological parameters and gene expression. Sparse PLS analysis revealed complex molecular interaction networks of molecular and physiological data. Early responses prevented phototoxicity by reducing photosystem activity and the electron transfer chain together with the accumulation of photoprotectors and photorespiration. Apart from the reduction in photosynthesis as consequence of the direct UV damage on the photosystems, the primary metabolism was rearranged to deal with the oxidative stress while minimizing ROS production. New protein kinases and proteases related to signaling, coordination, and regulation of UV stress responses were revealed. All these processes demonstrate a complex molecular interaction network extending the current knowledge on UV-stress adaptation in pine.

  1. Comparative Proteomics of Mouse Tears and Saliva: Evidence from Large Protein Families for Functional Adaptation

    PubMed Central

    Karn, Robert C.; Laukaitis, Christina M.

    2015-01-01

    We produced a tear proteome of the genome mouse, C57BL/6, that contained 139 different protein identifications: 110 from a two-dimensional (2D) gel with subsequent trypsin digestion, 19 from a one-dimensional (1D) gel with subsequent trypsin digestion and ten from a 1D gel with subsequent Asp-N digestion. We compared this tear proteome with a C57BL/6 mouse saliva proteome produced previously. Sixteen of the 139 tear proteins are shared between the two proteomes, including six proteins that combat microbial growth. Among the 123 other tear proteins, were members of four large protein families that have no counterparts in humans: Androgen-binding proteins (ABPs) with different members expressed in the two proteomes, Exocrine secreted peptides (ESPs) expressed exclusively in the tear proteome, major urinary proteins (MUPs) expressed in one or both proteomes and the mouse-specific Kallikreins (subfamily b KLKs) expressed exclusively in the saliva proteome. All four families have members with suggested roles in mouse communication, which may influence some aspect of reproductive behavior. We discuss this in the context of functional adaptation involving tear and saliva proteins in the secretions of mouse lacrimal and salivary glands, respectively.

  2. Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

    PubMed Central

    Karn, Robert C.; Chung, Amanda G.; Laukaitis, Christina M.

    2013-01-01

    The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6) and the genome rat (BN/SsNHsd/Mcwi). Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals. PMID:24926433

  3. Abiotic stress responses in plants: roles of calmodulin-regulated proteins

    PubMed Central

    Virdi, Amardeep S.; Singh, Supreet; Singh, Prabhjeet

    2015-01-01

    Intracellular changes in calcium ions (Ca2+) in response to different biotic and abiotic stimuli are detected by various sensor proteins in the plant cell. Calmodulin (CaM) is one of the most extensively studied Ca2+-sensing proteins and has been shown to be involved in transduction of Ca2+ signals. After interacting with Ca2+, CaM undergoes conformational change and influences the activities of a diverse range of CaM-binding proteins. A number of CaM-binding proteins have also been implicated in stress responses in plants, highlighting the central role played by CaM in adaptation to adverse environmental conditions. Stress adaptation in plants is a highly complex and multigenic response. Identification and characterization of CaM-modulated proteins in relation to different abiotic stresses could, therefore, prove to be essential for a deeper understanding of the molecular mechanisms involved in abiotic stress tolerance in plants. Various studies have revealed involvement of CaM in regulation of metal ions uptake, generation of reactive oxygen species and modulation of transcription factors such as CAMTA3, GTL1, and WRKY39. Activities of several kinases and phosphatases have also been shown to be modulated by CaM, thus providing further versatility to stress-associated signal transduction pathways. The results obtained from contemporary studies are consistent with the proposed role of CaM as an integrator of different stress signaling pathways, which allows plants to maintain homeostasis between different cellular processes. In this review, we have attempted to present the current state of understanding of the role of CaM in modulating different stress-regulated proteins and its implications in augmenting abiotic stress tolerance in plants. PMID:26528296

  4. The Role of Semidisorder in Temperature Adaptation of Bacterial FlgM Proteins

    PubMed Central

    Wang, Jihua; Yang, Yuedong; Cao, Zanxia; Li, Zhixiu; Zhao, Huiying; Zhou, Yaoqi

    2013-01-01

    Probabilities of disorder for FlgM proteins of 39 species whose optimal growth temperature ranges from 273 K (0°C) to 368 K (95°C) were predicted by a newly developed method called Sequence-based Prediction with Integrated NEural networks for Disorder (SPINE-D). We showed that the temperature-dependent behavior of FlgM proteins could be separated into two subgroups according to their sequence lengths. Only shorter sequences evolved to adapt to high temperatures (>318 K or 45°C). Their ability to adapt to high temperatures was achieved through a transition from a fully disordered state with little secondary structure to a semidisordered state with high predicted helical probability at the N-terminal region. The predicted results are consistent with available experimental data. An analysis of all orthologous protein families in 39 species suggests that such a transition from a fully disordered state to semidisordered and/or ordered states is one of the strategies employed by nature for adaptation to high temperatures. PMID:24314090

  5. Aging Is Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion

    PubMed Central

    Wall, Benjamin Toby; Gorissen, Stefan H.; Pennings, Bart; Koopman, René; Groen, Bart B. L.; Verdijk, Lex B.; van Loon, Luc J. C.

    2015-01-01

    Purpose Progressive loss of skeletal muscle mass with aging (sarcopenia) forms a global health concern. It has been suggested that an impaired capacity to increase muscle protein synthesis rates in response to protein intake is a key contributor to sarcopenia. We assessed whether differences in post-absorptive and/or post-prandial muscle protein synthesis rates exist between large cohorts of healthy young and older men. Procedures We performed a cross-sectional, retrospective study comparing in vivo post-absorptive muscle protein synthesis rates determined with stable isotope methodologies between 34 healthy young (22±1 y) and 72 older (75±1 y) men, and post-prandial muscle protein synthesis rates between 35 healthy young (22±1 y) and 40 older (74±1 y) men. Findings Post-absorptive muscle protein synthesis rates did not differ significantly between the young and older group. Post-prandial muscle protein synthesis rates were 16% lower in the older subjects when compared with the young. Muscle protein synthesis rates were >3 fold more responsive to dietary protein ingestion in the young. Irrespective of age, there was a strong negative correlation between post-absorptive muscle protein synthesis rates and the increase in muscle protein synthesis rate following protein ingestion. Conclusions Aging is associated with the development of muscle anabolic inflexibility which represents a key physiological mechanism underpinning sarcopenia. PMID:26536130

  6. Bioinformatics and variability in drug response: a protein structural perspective

    PubMed Central

    Lahti, Jennifer L.; Tang, Grace W.; Capriotti, Emidio; Liu, Tianyun; Altman, Russ B.

    2012-01-01

    Marketed drugs frequently perform worse in clinical practice than in the clinical trials on which their approval is based. Many therapeutic compounds are ineffective for a large subpopulation of patients to whom they are prescribed; worse, a significant fraction of patients experience adverse effects more severe than anticipated. The unacceptable risk–benefit profile for many drugs mandates a paradigm shift towards personalized medicine. However, prior to adoption of patient-specific approaches, it is useful to understand the molecular details underlying variable drug response among diverse patient populations. Over the past decade, progress in structural genomics led to an explosion of available three-dimensional structures of drug target proteins while efforts in pharmacogenetics offered insights into polymorphisms correlated with differential therapeutic outcomes. Together these advances provide the opportunity to examine how altered protein structures arising from genetic differences affect protein–drug interactions and, ultimately, drug response. In this review, we first summarize structural characteristics of protein targets and common mechanisms of drug interactions. Next, we describe the impact of coding mutations on protein structures and drug response. Finally, we highlight tools for analysing protein structures and protein–drug interactions and discuss their application for understanding altered drug responses associated with protein structural variants. PMID:22552919

  7. Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance.

    PubMed

    Raefsky, Sophia M; Mattson, Mark P

    2017-01-01

    An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans. The metabolic 'switch' in fuel source from liver glycogen store-derived glucose to adipose cell-derived fatty acids and their ketone metabolites during fasting and sustained exercise, appears to be a pivotal trigger of both brain-intrinsic and peripheral organ-derived signals that enhance learning and memory and underlying synaptic plasticity and neurogenesis. Brain-intrinsic extracellular signals include the excitatory neurotransmitter glutamate and the neurotrophic factor BDNF, and peripheral signals may include the liver-derived ketone 3-hydroxybutyrate and the muscle cell-derived protein irisin. Emerging findings suggest that fasting, exercise and an intellectually challenging lifestyle can protect neurons against the dysfunction and degeneration that they would otherwise suffer in acute brain injuries (stroke and head trauma) and neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease. Among the prominent intracellular responses of neurons to these bioenergetic challenges are up-regulation of antioxidant defenses, autophagy/mitophagy and DNA repair. A better understanding of such fundamental hormesis-based adaptive neuronal response mechanisms is expected to result in the development and implementation of novel interventions to promote optimal brain function and healthy brain aging.

  8. Effects of skeletal muscle energy availability on protein turnover responses to exercise.

    PubMed

    Smiles, William J; Hawley, John A; Camera, Donny M

    2016-01-01

    Skeletal muscle adaptation to exercise training is a consequence of repeated contraction-induced increases in gene expression that lead to the accumulation of functional proteins whose role is to blunt the homeostatic perturbations generated by escalations in energetic demand and substrate turnover. The development of a specific 'exercise phenotype' is the result of new, augmented steady-state mRNA and protein levels that stem from the training stimulus (i.e. endurance or resistance based). Maintaining appropriate skeletal muscle integrity to meet the demands of training (i.e. increases in myofibrillar and/or mitochondrial protein) is regulated by cyclic phases of synthesis and breakdown, the rate and turnover largely determined by the protein's half-life. Cross-talk among several intracellular systems regulating protein synthesis, breakdown and folding is required to ensure protein equilibrium is maintained. These pathways include both proteasomal and lysosomal degradation systems (ubiquitin-mediated and autophagy, respectively) and the protein translational and folding machinery. The activities of these cellular pathways are bioenergetically expensive and are modified by intracellular energy availability (i.e. macronutrient intake) and the 'training impulse' (i.e. summation of the volume, intensity and frequency). As such, exercise-nutrient interactions can modulate signal transduction cascades that converge on these protein regulatory systems, especially in the early post-exercise recovery period. This review focuses on the regulation of muscle protein synthetic response-adaptation processes to divergent exercise stimuli and how intracellular energy availability interacts with contractile activity to impact on muscle remodelling.

  9. Ionotropic glutamate receptors mediate OFF responses in light-adapted ON bipolar cells

    PubMed Central

    Pang, Ji-Jie; Gao, Fan; Wu, Samuel M.

    2013-01-01

    Previous studies have suggested that photoreceptor synaptic inputs to depolarizing bipolar cells (DBCs or ON bipolar cells) are mediated by mGluR6 receptors and those to hyperpolarizing bipolar cells (HBCs or OFF bipolar cells) are mediated by AMPA/kainate receptors. Here we show that in addition to mGluR6 receptors which mediate the sign-inverting, depolarizing light responses, subpopulations of cone-dominated and rod/cone mixed DBCs use GluR4 AMPA receptors to generate a transient sign-preserving OFF response under light adapted conditions. These AMPA receptors are located at the basal junctions postsynaptic to rods and they are silent under dark-adapted conditions, as tonic glutamate release in darkness desensitizes these receptors. Light adaptation enhances rod-cone coupling and thus allows cone photocurrents with an abrupt OFF depolarization to enter the rods. The abrupt rod depolarization triggers glutamate activation of unoccupied AMPA receptors, resulting in a transient OFF response in DBCs. It has been widely accepted that the DNQX-sensitive, OFF transient responses in retinal amacrine cells and ganglion cells are mediated exclusively by HBCs. Our results suggests that this view needs revision as AMPA receptors in subpopulations of DBCs are likely to significantly contribute to the DNQX-sensitive OFF transient responses in light-adapted third- and higher-order visual neurons. PMID:22842089

  10. Meeting Report: Structural Determination of Environmentally Responsive Proteins

    PubMed Central

    Reinlib, Leslie

    2005-01-01

    The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein–protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health. PMID:16263521

  11. Responsive block copolymer photonics triggered by protein-polyelectrolyte coacervation.

    PubMed

    Fan, Yin; Tang, Shengchang; Thomas, Edwin L; Olsen, Bradley D

    2014-11-25

    Ionic interactions between proteins and polyelectrolytes are demonstrated as a method to trigger responsive transitions in block copolymer (BCP) photonic gels containing one neutral hydrophobic block and one cationic hydrophilic block. Poly(2-vinylpyridine) (P2VP) blocks in lamellar poly(styrene-b-2-vinylpyridine) block copolymer thin films are quaternized with primary bromides to yield swollen gels that show strong reflectivity peaks in the visible range; exposure to aqueous solutions of various proteins alters the swelling ratios of the quaternized P2VP (QP2VP) gel layers in the PS-QP2VP materials due to the ionic interactions between proteins and the polyelectrolyte. Parameters such as charge density, hydrophobicity, and cross-link density of the QP2VP gel layers as well as the charge and size of the proteins play significant roles on the photonic responses of the BCP gels. Differences in the size and pH-dependent charge of proteins provide a basis for fingerprinting proteins based on their temporal and equilibrium photonic response. The results demonstrate that the BCP gels and their photonic effect provide a robust and visually interpretable method to differentiate different proteins.

  12. Common Bean: A Legume Model on the Rise for Unraveling Responses and Adaptations to Iron, Zinc, and Phosphate Deficiencies

    PubMed Central

    Castro-Guerrero, Norma A.; Isidra-Arellano, Mariel C.; Mendoza-Cozatl, David G.; Valdés-López, Oswaldo

    2016-01-01

    Common bean (Phaseolus vulgaris) was domesticated ∼8000 years ago in the Americas and today is a staple food worldwide. Besides caloric intake, common bean is also an important source of protein and micronutrients and it is widely appreciated in developing countries for their affordability (compared to animal protein) and its long storage life. As a legume, common bean also has the economic and environmental benefit of associating with nitrogen-fixing bacteria, thus reducing the use of synthetic fertilizers, which is key for sustainable agriculture. Despite significant advances in the plant nutrition field, the mechanisms underlying the adaptation of common bean to low nutrient input remains largely unknown. The recent release of the common bean genome offers, for the first time, the possibility of applying techniques and approaches that have been exclusive to model plants to study the adaptive responses of common bean to challenging environments. In this review, we discuss the hallmarks of common bean domestication and subsequent distribution around the globe. We also discuss recent advances in phosphate, iron, and zinc homeostasis, as these nutrients often limit plant growth, development, and yield. In addition, iron and zinc are major targets of crop biofortification to improve human nutrition. Developing common bean varieties able to thrive under nutrient limiting conditions will have a major impact on human nutrition, particularly in countries where dry beans are the main source of carbohydrates, protein and minerals. PMID:27200068

  13. Common Bean: A Legume Model on the Rise for Unraveling Responses and Adaptations to Iron, Zinc, and Phosphate Deficiencies.

    PubMed

    Castro-Guerrero, Norma A; Isidra-Arellano, Mariel C; Mendoza-Cozatl, David G; Valdés-López, Oswaldo

    2016-01-01

    Common bean (Phaseolus vulgaris) was domesticated ∼8000 years ago in the Americas and today is a staple food worldwide. Besides caloric intake, common bean is also an important source of protein and micronutrients and it is widely appreciated in developing countries for their affordability (compared to animal protein) and its long storage life. As a legume, common bean also has the economic and environmental benefit of associating with nitrogen-fixing bacteria, thus reducing the use of synthetic fertilizers, which is key for sustainable agriculture. Despite significant advances in the plant nutrition field, the mechanisms underlying the adaptation of common bean to low nutrient input remains largely unknown. The recent release of the common bean genome offers, for the first time, the possibility of applying techniques and approaches that have been exclusive to model plants to study the adaptive responses of common bean to challenging environments. In this review, we discuss the hallmarks of common bean domestication and subsequent distribution around the globe. We also discuss recent advances in phosphate, iron, and zinc homeostasis, as these nutrients often limit plant growth, development, and yield. In addition, iron and zinc are major targets of crop biofortification to improve human nutrition. Developing common bean varieties able to thrive under nutrient limiting conditions will have a major impact on human nutrition, particularly in countries where dry beans are the main source of carbohydrates, protein and minerals.

  14. Adaptive responses reveal contemporary and future ecotypes in a desert shrub.

    PubMed

    Richardson, Bryce A; Kitchen, Stanley G; Pendleton, Rosemary L; Pendleton, Burton K; Germino, Matthew J; Rehfeldt, Gerald E; Meyer, Susan E

    2014-03-01

    Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species-climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep dines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are needed

  15. Adaptive responses reveal contemporary and future ecotypes in a desert shrub

    USGS Publications Warehouse

    Richardson, Bryce A.; Kitchen, Stanley G.; Pendleton, Rosemary L.; Pendleton, Burton K.; Germino, Matthew J.; Rehfeldt, Gerald E.; Meyer, Susan E.

    2014-01-01

    Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species–climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep clines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are

  16. Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

    SciTech Connect

    Conolly, Rory B. . E-mail: Conolly.Rory@epa.gov; Gaylor, David W.; Lutz, Werner K.

    2005-09-01

    Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health.

  17. Identification of iron-responsive proteins expressed by Chlamydia trachomatis reticulate bodies during intracellular growth.

    PubMed

    Dill, Brian D; Dessus-Babus, Sophie; Raulston, Jane E

    2009-01-01

    The obligate intracellular bacterium Chlamydia trachomatis serovar E is the most prevalent cause of bacterial sexually transmitted disease. With an established requirement for iron, the developmental cycle arrests at the intracellular reticulate body stage during iron restriction, resulting in a phenomenon termed persistence. Persistence has implications in natural infections for altered expression of virulence factors and antigens, in addition to a potential role in producing chronic infection. In this study, chlamydial proteins in iron-restricted, infected HEC-1B cells were radiolabelled during mid-developmental cycle growth, harvested, and separated using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Of approximately 250 radiolabelled protein species visualized, densitometric analysis revealed 25 proteins that increased in expression under iron restriction compared to iron-sufficient control samples; ten protein species identified by mass spectrometry are involved in the oxidative damage response (alkyl hydroperoxide reductase, 6-phosphogluconolactonase and acyl carrier protein synthase), transcription (RNA polymerase subunit alpha and transcription anti-termination factors NusA and NusG), protein modification (peptide deformylase and trigger factor), and virulence (Chlamydia protein associating with death domains, CADD). Transcript-level expression patterns of ahpC, devB, cadd, fabF and ct538 were measured by quantitative RT-PCR throughout the developmental cycle, and each gene examined demonstrated a significant but small mid-cycle increase in transcript level in iron-restricted cultures compared to iron-replete controls. Taken together, these data suggest that the primary response of chlamydiae to reduced iron availability is to increase expression of proteins involved in protection against oxidative damage via iron-catalysed generation of reactive oxygen species and adaptation to stress by increasing expression of transcriptional machinery

  18. Modeling Light Adaptation in Circadian Clock: Prediction of the Response That Stabilizes Entrainment

    PubMed Central

    Yoshinaga, Tetsuya; Aihara, Kazuyuki

    2011-01-01

    Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature. PMID:21698191

  19. Kinetic Stability of Proteins in Beans and Peas: Implications for Protein Digestibility, Seed Germination, and Plant Adaptation.

    PubMed

    Xia, Ke; Pittelli, Sandy; Church, Jennifer; Colón, Wilfredo

    2016-10-12

    Kinetically stable proteins (KSPs) are resistant to the denaturing detergent sodium dodecyl sulfate (SDS). Such resilience makes KSPs resistant to proteolytic degradation and may have arisen in nature as a mechanism for organismal adaptation and survival against harsh conditions. Legumes are well-known for possessing degradation-resistant proteins that often diminish their nutritional value. Here we applied diagonal two-dimensional (D2D) SDS-polyacrylamide gel electrophoresis (PAGE), a method that allows for the proteomics-level identification of KSPs, to a group of 12 legumes (mostly beans and peas) of agricultural and nutritional importance. Our proteomics results show beans that are more difficult to digest, such as soybean, lima beans, and various common beans, have high contents of KSPs. In contrast, mung bean, red lentil, and various peas that are highly digestible contain low amounts of KSPs. Identified proteins with high kinetic stability are associated with warm-season beans, which germinate at higher temperatures. In contrast, peas and red lentil, which are cool-season legumes, contain low levels of KSPs. Thus, our results show protein kinetic stability is an important factor in the digestibility of legume proteins and may relate to nutrition efficiency, timing of seed germination, and legume resistance to biotic stressors. Furthermore, we show D2D SDS-PAGE is a powerful method that could be applied for determining the abundance and identity of KSPs in engineered and wild legumes and for advancing basic research and associated applications.

  20. Adaptive response to acetic acid in the highly resistant yeast species Zygosaccharomyces bailii revealed by quantitative proteomics.

    PubMed

    Guerreiro, Joana F; Mira, Nuno P; Sá-Correia, Isabel

    2012-08-01

    Zygosaccharomyces bailii is the most tolerant yeast species to acetic acid-induced toxicity, being able to grow in the presence of concentrations of this food preservative close to the legal limits. For this reason, Z. bailii is the most important microbial contaminant of acidic food products but the mechanisms behind this intrinsic resistance to acetic acid are very poorly characterized. To gain insights into the adaptive response and tolerance to acetic acid in Z. bailii, we explored an expression proteomics approach, based on quantitative 2DE, to identify alterations occurring in the protein content in response to sudden exposure or balanced growth in the presence of an inhibitory but nonlethal concentration of this weak acid. A coordinate increase in the content of proteins involved in cellular metabolism, in particular, in carbohydrate metabolism (Mdh1p, Aco1p, Cit1p, Idh2p, and Lpd1p) and energy generation (Atp1p and Atp2p), as well as in general and oxidative stress response (Sod2p, Dak2p, Omp2p) was registered. Results reinforce the concept that glucose and acetic acid are coconsumed in Z. bailii, with acetate being channeled into the tricarboxylic acid cycle. When acetic acid is the sole carbon source, results suggest the activation of gluconeogenic and pentose phosphate pathways, based on the increased content of several proteins of these pathways after glucose exhaustion.

  1. Heat Shock Partially Dissociates the Overlapping Modules of the Yeast Protein-Protein Interaction Network: A Systems Level Model of Adaptation

    PubMed Central

    Mihalik, Ágoston; Csermely, Peter

    2011-01-01

    Network analysis became a powerful tool giving new insights to the understanding of cellular behavior. Heat shock, the archetype of stress responses, is a well-characterized and simple model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a ‘stratus-cumulus’ type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes. PMID:22022244

  2. Natural variation in abiotic stress responsive gene expression and local adaptation to climate in Arabidopsis thaliana.

    PubMed

    Lasky, Jesse R; Des Marais, David L; Lowry, David B; Povolotskaya, Inna; McKay, John K; Richards, James H; Keitt, Timothy H; Juenger, Thomas E

    2014-09-01

    Gene expression varies widely in natural populations, yet the proximate and ultimate causes of this variation are poorly known. Understanding how variation in gene expression affects abiotic stress tolerance, fitness, and adaptation is central to the field of evolutionary genetics. We tested the hypothesis that genes with natural genetic variation in their expression responses to abiotic stress are likely to be involved in local adaptation to climate in Arabidopsis thaliana. Specifically, we compared genes with consistent expression responses to environmental stress (expression stress responsive, "eSR") to genes with genetically variable responses to abiotic stress (expression genotype-by-environment interaction, "eGEI"). We found that on average genes that exhibited eGEI in response to drought or cold had greater polymorphism in promoter regions and stronger associations with climate than those of eSR genes or genomic controls. We also found that transcription factor binding sites known to respond to environmental stressors, especially abscisic acid responsive elements, showed significantly higher polymorphism in drought eGEI genes in comparison to eSR genes. By contrast, eSR genes tended to exhibit relatively greater pairwise haplotype sharing, lower promoter diversity, and fewer nonsynonymous polymorphisms, suggesting purifying selection or selective sweeps. Our results indicate that cis-regulatory evolution and genetic variation in stress responsive gene expression may be important mechanisms of local adaptation to climatic selective gradients.

  3. Inhibition of glutathione synthesis eliminates the adaptive response of ascitic hepatoma 22 cells to nedaplatin that targets thioredoxin reductase

    SciTech Connect

    Wang, Yijun; Lu, Hongjuan; Wang, Dongxu; Li, Shengrong; Sun, Kang; Wan, Xiaochun; Taylor, Ethan Will; Zhang, Jinsong

    2012-12-15

    Thioredoxin reductase (TrxR) is a target for cancer therapy and the anticancer mechanism of cisplatin involves TrxR inhibition. We hypothesize that the anticancer drug nedaplatin (NDP), an analogue of cisplatin and a second-generation platinum complex, also targets TrxR. Furthermore, we investigate whether the therapeutic efficacy of NDP can be enhanced by simultaneous modulation of 1) TrxR, via NDP, and 2) glutathione (GSH), via the GSH synthesis inhibitor buthionine sulfoximine (BSO). Mice bearing ascitic hepatoma 22 (H22) cells were treated with NDP alone or NDP plus BSO. TrxR activity of H22 cells was inhibited by NDP in a dose-dependent manner. A high correlation between the inhibition of TrxR activity at 6 h and the inhibition of ascitic fluid volume at 72 h was established (r = 0.978, p < 0.01). As an adaptive response, the viable ascitic cancer cells after NDP treatment displayed an enlarged cell phenotype, assembled with several-fold more antioxidant enzymes and GSH-predominant non-protein free thiols. This adaptive response was largely eliminated when BSO was co-administered with NDP, leading to the decimation of the H22 cell population without enhancing renal toxicity, since at this dose, NDP did not inhibit renal TrxR activity. In conclusion, the pharmacological effect of NDP involves TrxR inhibition, and the adaptive response of NDP-treated ascitic H22 cells can be efficiently counteracted by BSO. Simultaneous modulation of TrxR and GSH on ascitic H22 cells using NDP plus BSO greatly enhances therapeutic efficacy as compared with the single modulation of TrxR using NDP alone. -- Highlights: ► Nedaplatin at a pharmacological dose inhibits TrxR in cancer cells but not in kidney. ► The nedaplatin-treated cancer cells exhibit adaptive response. ► Buthionine sulfoximine inhibits glutathione in both cancer cells and kidney. ► Buthionine sulfoximine counteracts the adaptive response to the nedaplatin treatment. ► Buthionine sulfoximine does not

  4. Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae.

    PubMed Central

    Shenton, Daniel; Grant, Chris M

    2003-01-01

    The irreversible oxidation of cysteine residues can be prevented by protein S-thiolation, a process by which protein SH groups form mixed disulphides with low-molecular-mass thiols such as glutathione. We report here the target proteins which are modified in yeast cells in response to H(2)O(2). In particular, a range of glycolytic and related enzymes (Tdh3, Eno2, Adh1, Tpi1, Ald6 and Fba1), as well as translation factors (Tef2, Tef5, Nip1 and Rps5) are identified. The oxidative stress conditions used to induce S-thiolation are shown to inhibit GAPDH (glyceraldehyde-3-phosphate dehydrogenase), enolase and alcohol dehydrogenase activities, whereas they have no effect on aldolase, triose phosphate isomerase or aldehyde dehydrogenase activities. The inhibition of GAPDH, enolase and alcohol dehydrogenase is readily reversible once the oxidant is removed. In addition, we show that peroxide stress has little or no effect on glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, the enzymes that catalyse NADPH production via the pentose phosphate pathway. Thus the inhibition of glycolytic flux is proposed to result in glucose equivalents entering the pentose phosphate pathway for the generation of NADPH. Radiolabelling is used to confirm that peroxide stress results in a rapid and reversible inhibition of protein synthesis. Furthermore, we show that glycolytic enzyme activities and protein synthesis are irreversibly inhibited in a mutant that lacks glutathione, and hence cannot modify proteins by S-thiolation. In summary, protein S-thiolation appears to serve an adaptive function during exposure to an oxidative stress by reprogramming metabolism and protecting protein synthesis against irreversible oxidation. PMID:12755685

  5. The stress response system of proteins: Implications for bioreactor scaleup

    NASA Technical Reports Server (NTRS)

    Goochee, Charles F.

    1988-01-01

    Animal cells face a variety of environmental stresses in large scale bioreactors, including periodic variations in shear stress and dissolved oxygen concentration. Diagnostic techniques were developed for identifying the particular sources of environmental stresses for animal cells in a given bioreactor configuration. The mechanisms by which cells cope with such stresses was examined. The individual concentrations and synthesis rates of hundreds of intracellular proteins are affected by the extracellular environment (medium composition, dissolved oxygen concentration, ph, and level of surface shear stress). Techniques are currently being developed for quantifying the synthesis rates and concentrations of the intracellular proteins which are most sensitive to environmental stress. Previous research has demonstrated that a particular set of stress response proteins are synthesized by mammalian cells in response to temperature fluctuations, dissolved oxygen deprivation, and glucose deprivation. Recently, it was demonstrated that exposure of human kidney cells to high shear stress results in expression of a completely distinct set of intracellular proteins.

  6. Systematic identification of genes and transduction pathways involved in radio-adaptive response

    SciTech Connect

    Wu, Honglu

    2015-05-22

    Low doses of radiation have been shown to protect against the biological effects of later exposure to toxic levels of radiation. In this study, we propose to identify the molecular mechanisms of this adaptive response by systematically identifying the genes that play a role in radio-protection. In the original proposal, a human cell line that is well-documented to exhibit the radio-adaptive effect was to be used. In this revised study plan, we will use a mouse model, C57BL/6, which has also been well investigated for radio-adaptation. The goal of the proposed study is to enhance our understanding of cellular responses to low doses of radiation exposure at the molecular level.

  7. Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

    SciTech Connect

    Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

    2009-02-25

    Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

  8. Integrating human responses to climate change into conservation vulnerability assessments and adaptation planning.

    PubMed

    Maxwell, Sean L; Venter, Oscar; Jones, Kendall R; Watson, James E M

    2015-10-01

    The impact of climate change on biodiversity is now evident, with the direct impacts of changing temperature and rainfall patterns and increases in the magnitude and frequency of extreme events on species distribution, populations, and overall ecosystem function being increasingly publicized. Changes in the climate system are also affecting human communities, and a range of human responses across terrestrial and marine realms have been witnessed, including altered agricultural activities, shifting fishing efforts, and human migration. Failing to account for the human responses to climate change is likely to compromise climate-smart conservation efforts. Here, we use a well-established conservation planning framework to show how integrating human responses to climate change into both species- and site-based vulnerability assessments and adaptation plans is possible. By explicitly taking into account human responses, conservation practitioners will improve their evaluation of species and ecosystem vulnerability, and will be better able to deliver win-wins for human- and biodiversity-focused climate adaptation.

  9. Emergence of tissue sensitivity to Hox protein levels underlies the evolution of an adaptive morphological trait

    PubMed Central

    Refki, Peter Nagui; Armisén, David; Crumière, Antonin Jean Johan; Viala, Séverine; Khila, Abderrahman

    2014-01-01

    Growth control scales morphological attributes and, therefore, provides a critical contribution to the evolution of adaptive traits. Yet, the genetic mechanisms underlying growth in the context of specific ecological adaptations are poorly understood. In water striders, adaptation to locomotion on the water surface is associated with allometric and functional changes in thoracic appendages, such that T2-legs, used as propelling oars, are longer than T3-legs, used as steering rudders. The Hox gene Ubx establishes this derived morphology by elongating T2-legs but shortening T3-legs. Using gene expression assays, RNAi knockdown, and comparative transcriptomics, we demonstrate that the evolution of water surface rowing as a novel means of locomotion is associated with the evolution of a dose-dependent promoting-repressing effect of Ubx on leg growth. In the water strider Limnoporus dissortis, T3-legs express six to seven times higher levels of Ubx compared to T2-legs. Ubx RNAi shortens T2-legs and the severity of this phenotype increases with increased depletion of Ubx protein. Conversely, Ubx RNAi lengthens T3-legs but this phenotype is partially rescued when Ubx protein is further depleted. This dose-dependent effect of Ubx on leg growth is absent in non-rowing relatives that retain the ancestral relative leg length. We also show that the spatial patterns of expression of dpp, wg, hh, egfr, dll, exd, hth, and dac are unchanged in Ubx RNAi treatments. This indicates that the dose-dependent opposite effect of Ubx on T2- and T3-legs operates without any apparent effect on the spatial expression of major leg patterning genes. Our data suggest that scaling of adaptive allometries can evolve through changes in the levels of expression of Hox proteins early during ontogeny, and in the sensitivity of the tissues that express them, without any major effects on pattern formation. PMID:24886828

  10. Median Modified Wiener Filter for nonlinear adaptive spatial denoising of protein NMR multidimensional spectra.

    PubMed

    Cannistraci, Carlo Vittorio; Abbas, Ahmed; Gao, Xin

    2015-01-26

    Denoising multidimensional NMR-spectra is a fundamental step in NMR protein structure determination. The state-of-the-art method uses wavelet-denoising, which may suffer when applied to non-stationary signals affected by Gaussian-white-noise mixed with strong impulsive artifacts, like those in multi-dimensional NMR-spectra. Regrettably, Wavelet's performance depends on a combinatorial search of wavelet shapes and parameters; and multi-dimensional extension of wavelet-denoising is highly non-trivial, which hampers its application to multidimensional NMR-spectra. Here, we endorse a diverse philosophy of denoising NMR-spectra: less is more! We consider spatial filters that have only one parameter to tune: the window-size. We propose, for the first time, the 3D extension of the median-modified-Wiener-filter (MMWF), an adaptive variant of the median-filter, and also its novel variation named MMWF*. We test the proposed filters and the Wiener-filter, an adaptive variant of the mean-filter, on a benchmark set that contains 16 two-dimensional and three-dimensional NMR-spectra extracted from eight proteins. Our results demonstrate that the adaptive spatial filters significantly outperform their non-adaptive versions. The performance of the new MMWF* on 2D/3D-spectra is even better than wavelet-denoising. Noticeably, MMWF* produces stable high performance almost invariant for diverse window-size settings: this signifies a consistent advantage in the implementation of automatic pipelines for protein NMR-spectra analysis.

  11. Median Modified Wiener Filter for nonlinear adaptive spatial denoising of protein NMR multidimensional spectra

    PubMed Central

    Cannistraci, Carlo Vittorio; Abbas, Ahmed; Gao, Xin

    2015-01-01

    Denoising multidimensional NMR-spectra is a fundamental step in NMR protein structure determination. The state-of-the-art method uses wavelet-denoising, which may suffer when applied to non-stationary signals affected by Gaussian-white-noise mixed with strong impulsive artifacts, like those in multi-dimensional NMR-spectra. Regrettably, Wavelet's performance depends on a combinatorial search of wavelet shapes and parameters; and multi-dimensional extension of wavelet-denoising is highly non-trivial, which hampers its application to multidimensional NMR-spectra. Here, we endorse a diverse philosophy of denoising NMR-spectra: less is more! We consider spatial filters that have only one parameter to tune: the window-size. We propose, for the first time, the 3D extension of the median-modified-Wiener-filter (MMWF), an adaptive variant of the median-filter, and also its novel variation named MMWF*. We test the proposed filters and the Wiener-filter, an adaptive variant of the mean-filter, on a benchmark set that contains 16 two-dimensional and three-dimensional NMR-spectra extracted from eight proteins. Our results demonstrate that the adaptive spatial filters significantly outperform their non-adaptive versions. The performance of the new MMWF* on 2D/3D-spectra is even better than wavelet-denoising. Noticeably, MMWF* produces stable high performance almost invariant for diverse window-size settings: this signifies a consistent advantage in the implementation of automatic pipelines for protein NMR-spectra analysis. PMID:25619991

  12. Adaptive Evolution of Eel Fluorescent Proteins from Fatty Acid Binding Proteins Produces Bright Fluorescence in the Marine Environment

    PubMed Central

    Gruber, David F.; Gaffney, Jean P.; Mehr, Shaadi; DeSalle, Rob; Sparks, John S.; Platisa, Jelena; Pieribone, Vincent A.

    2015-01-01

    We report the identification and characterization of two new members of a family of bilirubin-inducible fluorescent proteins (FPs) from marine chlopsid eels and demonstrate a key region of the sequence that serves as an evolutionary switch from non-fluorescent to fluorescent fatty acid-binding proteins (FABPs). Using transcriptomic analysis of two species of brightly fluorescent Kaupichthys eels (Kaupichthys hyoproroides and Kaupichthys n. sp.), two new FPs were identified, cloned and characterized (Chlopsid FP I and Chlopsid FP II). We then performed phylogenetic analysis on 210 FABPs, spanning 16 vertebrate orders, and including 163 vertebrate taxa. We show that the fluorescent FPs diverged as a protein family and are the sister group to brain FABPs. Our results indicate that the evolution of this family involved at least three gene duplication events. We show that fluorescent FABPs possess a unique, conserved tripeptide Gly-Pro-Pro sequence motif, which is not found in non-fluorescent fatty acid binding proteins. This motif arose from a duplication event of the FABP brain isoforms and was under strong purifying selection, leading to the classification of this new FP family. Residues adjacent to the motif are under strong positive selection, suggesting a further refinement of the eel protein’s fluorescent properties. We present a phylogenetic reconstruction of this emerging FP family and describe additional fluorescent FABP members from groups of distantly related eels. The elucidation of this class of fish FPs with diverse properties provides new templates for the development of protein-based fluorescent tools. The evolutionary adaptation from fatty acid-binding proteins to fluorescent fatty acid-binding proteins raises intrigue as to the functional role of bright green fluorescence in this cryptic genus of reclusive eels that inhabit a blue, nearly monochromatic, marine environment. PMID:26561348

  13. Heat shock proteins and exercise adaptations. Our knowledge thus far and the road still ahead.

    PubMed

    Henstridge, Darren C; Febbraio, Mark A; Hargreaves, Mark

    2016-03-15

    By its very nature, exercise exerts a challenge to the body's cellular homeostatic mechanisms. This homeostatic challenge affects not only the contracting skeletal muscle but also a number of other organs and results over time in exercise-induced adaptations. Thus it is no surprise that heat shock proteins (HSPs), a group of ancient and highly conserved cytoprotective proteins critical in the maintenance of protein and cellular homeostasis, have been implicated in exercise/activity-induced adaptations. It has become evident that HSPs such as HSP72 are induced or activated with acute exercise or after chronic exercise training regimens. These observations have given scientists an insight into the protective mechanisms of these proteins and provided an opportunity to exploit their protective role to improve health and physical performance. Although our knowledge in this area of physiology has improved dramatically, many questions still remain unanswered. Further understanding of the role of HSPs in exercise physiology may prove beneficial for therapeutic targeting in diseased patient cohorts, exercise prescription for disease prevention, and training strategies for elite athletes.

  14. Stability of adaptive cruise control systems taking account of vehicle response time and delay

    NASA Astrophysics Data System (ADS)

    Davis, L. C.

    2012-08-01

    The region of string stability of a platoon of adaptive cruise control vehicles, taking into account the delay and response of the vehicle powertrain, is found. An upper bound on the explicit delay time as a function the first-order powertrain response time constant is determined. The system is characterized by a headway time constant, a sensitivity parameter, relative (to the vehicle immediately in front) velocity control, and delayed-velocity feedback or acceleration feedback.

  15. The Host Immune Response to Streptococcus pneumoniae: Bridging Innate and Adaptive Immunity

    DTIC Science & Technology

    2006-07-06

    caused by penicillin -resistant Streptococcus pneumoniae in rabbits. Antimicrob. Agents Chemother. 46: 1760- 1765. Takeuchi, O., Hoshino, K., and...2006 2. REPORT TYPE 3. DATES COVERED 00-00-2006 to 00-00-2006 4. TITLE AND SUBTITLE The host immune response to Streptococcus pneumoniae ...host immune response to Streptococcus pneumoniae : bridging innate and adaptive immunity Katherine Shi-Hui Lee Thesis directed by: Clifford M

  16. BYSTANDER EFFECTS GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIAION AND CHEMICAL EXPOSURES

    EPA Science Inventory

    BYSTANDER EFFECTS, GENOMIC INSTABILITY, ADAPTIVE RESPONSE AND CANCER RISK ASSESSMENT FOR RADIATION AND CHEMICAL EXPOSURES

    R. Julian Preston
    Environmental Carcinogenesis Division, U.S. Environmental Protection Agency, Research Triangle Park, N.C. 27711, USA

    There ...

  17. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    EPA Science Inventory

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  18. Operational Characteristics of Adaptive Testing Procedures Using the Graded Response Model.

    ERIC Educational Resources Information Center

    Dodd, Barbara G.; And Others

    1989-01-01

    General guidelines are developed to assist practitioners in devising operational computerized adaptive testing systems based on the graded response model. The effects of the following major variables were examined: item pool size; stepsize used along the trait continuum until maximum likelihood estimation could be calculated; and stopping rule…

  19. Item Response Theory and Computerized Adaptive Testing Conference Proceedings (Wayzata, Minnesota, July 27-30, 1982).

    ERIC Educational Resources Information Center

    Weiss, David J., Ed.

    This report contains the Proceedings of the 1982 Item Response Theory and Computerized Adaptive Testing Conference. The papers and their discussions are organized into eight sessions: (1) "Developments in Latent Trait Theory," with papers by Fumiko Samejima and Michael V. Levine; (2) "Parameter Estimation," with papers by…

  20. {sub p}53-Dependent Adaptive Responses in Human Cells Exposed to Space Radiations

    SciTech Connect

    Takahashi, Akihisa; Su Xiaoming; Suzuki, Hiromi; Omori, Katsunori; Seki, Masaya; Hashizume, Toko; Shimazu, Toru; Ishioka, Noriaki; Iwasaki, Toshiyasu; Ohnishi, Takeo

    2010-11-15

    Purpose: It has been reported that priming irradiation or conditioning irradiation with a low dose of X-rays in the range of 0.02-0.1 Gy induces a p53-dependent adaptive response in mammalian cells. The aim of the present study was to clarify the effect of space radiations on the adaptive response. Methods and Materials: Two human lymphoblastoid cell lines were used; one cell line bears a wild-type p53 (wtp53) gene, and another cell line bears a mutated p53 (mp53) gene. The cells were frozen during transportation on the space shuttle and while in orbit in the International Space Station freezer for 133 days between November 15, 2008 and March 29, 2009. After the frozen samples were returned to Earth, the cells were cultured for 6 h and then exposed to a challenging X-ray-irradiation (2 Gy). Cellular sensitivity, apoptosis, and chromosome aberrations were scored using dye-exclusion assays, Hoechst33342 staining assays, and chromosomal banding techniques, respectively. Results: In cells exposed to space radiations, adaptive responses such as the induction of radioresistance and the depression of radiation-induced apoptosis and chromosome aberrations were observed in wtp53 cells but not in mp53 cells. Conclusion: These results have confirmed the hypothesis that p53-dependent adaptive responses are apparently induced by space radiations within a specific range of low doses. The cells exhibited this effect owing to space radiations exposure, even though the doses in space were very low.

  1. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection of pregnant cows with noncytopathic (ncp) BVDV induces rapid innate and adaptive immune responses resulting in clearance of the virus in less than 3 weeks. Seven to 14 days after inoculation of the cow, ncpBVDV crosses the placenta and induces a fetal viremia. Establishment of persistent ...

  2. Microswitch Clusters Promote Adaptive Responses and Reduce Finger Mouthing in a Boy with Multiple Disabilities

    ERIC Educational Resources Information Center

    Lancioni, Giulio E.; O'reilly, Mark F.; Singh, Nirbhay N.; Sigafoos, Jeff; Oliva, Doretta; Baccani, Simona; Groeneweg, Jop

    2006-01-01

    The authors assessed new microswitch clusters (i.e., combinations of two microswitches) and contingent stimulation to increase adaptive responses (i.e., foot and head movements) and reduce aberrant behavior (i.e., finger mouthing) in a boy with multiple disabilities. Initially, intervention was directed at increasing the frequency of each adaptive…

  3. Starvation stress during larval development reveals predictive adaptive response in adult worker honey bees (Apis mellifera)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A variety of organisms exhibit developmental plasticity that results in differences in adult morphology, physiology or behavior. This variation in the phenotype, called “Predictive Adaptive Response (PAR),” gives a selective advantage in an adult's environment if the adult experiences environments s...

  4. Rhetorical Dissent as an Adaptive Response to Classroom Problems: A Test of Protection Motivation Theory

    ERIC Educational Resources Information Center

    Bolkan, San; Goodboy, Alan K.

    2016-01-01

    Protection motivation theory (PMT) explains people's adaptive behavior in response to personal threats. In this study, PMT was used to predict rhetorical dissent episodes related to 210 student reports of perceived classroom problems. In line with theoretical predictions, a moderated moderation analysis revealed that students were likely to voice…

  5. Adaptive response studies may help choose astronauts for long-term space travel.

    PubMed

    Mortazavi, S M; Cameron, J R; Niroomand-rad, A

    2003-01-01

    Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections.

  6. Firestar-"D": Computerized Adaptive Testing Simulation Program for Dichotomous Item Response Theory Models

    ERIC Educational Resources Information Center

    Choi, Seung W.; Podrabsky, Tracy; McKinney, Natalie

    2012-01-01

    Computerized adaptive testing (CAT) enables efficient and flexible measurement of latent constructs. The majority of educational and cognitive measurement constructs are based on dichotomous item response theory (IRT) models. An integral part of developing various components of a CAT system is conducting simulations using both known and empirical…

  7. The Negatively Charged Regions of Lactoferrin Binding Protein B, an Adaptation against Anti-Microbial Peptides

    PubMed Central

    Morgenthau, Ari; Beddek, Amanda; Schryvers, Anthony B.

    2014-01-01

    Lactoferrin binding protein B (LbpB) is a bi-lobed membrane bound lipoprotein that is part of the lactoferrin receptor complex in a variety of Gram-negative pathogens. Despite high sequence diversity among LbpBs from various strains and species, a cluster of negatively charged amino acids is invariably present in the protein’s C-terminal lobe in all species except Moraxella bovis. The function of LbpB in iron acquisition has yet to be experimentally demonstrated, whereas in vitro studies have shown that LbpB confers protection against lactoferricin, a short cationic antimicrobial peptide released from the N- terminus of lactoferrin. In this study we demonstrate that the negatively charged regions can be removed from the Neisseria meningitidis LbpB without compromising stability, and this results in the inability of LbpB to protect against the bactericidal effects of lactoferricin. The release of LbpB from the cell surface by the autotransporter NalP reduces the protection against lactoferricin in the in vitro killing assay, attributed to removal of LbpB during washing steps, but is unlikely to have a similar impact in vivo. The protective effect of the negatively charged polysaccharide capsule in the killing assay was less than the protection conferred by LbpB, suggesting that LbpB plays a major role in protection against cationic antimicrobial peptides in vivo. The selective release of LbpB by NalP has been proposed to be a mechanism for evading the adaptive immune response, by reducing the antibody binding to the cell surface, but may also provide insights into the primary function of LbpB in vivo. Although TbpB and LbpB have been shown to be major targets of the human immune response, the selective release of LbpB suggests that unlike TbpB, LbpB may not be essential for iron acquisition, but important for protection against cationic antimicrobial peptides. PMID:24465982

  8. Cellular unfolded protein response against viruses used in gene therapy

    PubMed Central

    Sen, Dwaipayan; Balakrishnan, Balaji; Jayandharan, Giridhara R.

    2014-01-01

    Viruses are excellent vehicles for gene therapy due to their natural ability to infect and deliver the cargo to specific tissues with high efficiency. Although such vectors are usually “gutted” and are replication defective, they are subjected to clearance by the host cells by immune recognition and destruction. Unfolded protein response (UPR) is a naturally evolved cyto-protective signaling pathway which is triggered due to endoplasmic reticulum (ER) stress caused by accumulation of unfolded/misfolded proteins in its lumen. The UPR signaling consists of three signaling pathways, namely PKR-like ER kinase, activating transcription factor 6, and inositol-requiring protein-1. Once activated, UPR triggers the production of ER molecular chaperones and stress response proteins to help reduce the protein load within the ER. This occurs by degradation of the misfolded proteins and ensues in the arrest of protein translation machinery. If the burden of protein load in ER is beyond its processing capacity, UPR can activate pro-apoptotic pathways or autophagy leading to cell death. Viruses are naturally evolved in hijacking the host cellular translation machinery to generate a large amount of proteins. This phenomenon disrupts ER homeostasis and leads to ER stress. Alternatively, in the case of gutted vectors used in gene therapy, the excess load of recombinant vectors administered and encountered by the cell can trigger UPR. Thus, in the context of gene therapy, UPR becomes a major roadblock that can potentially trigger inflammatory responses against the vectors and reduce the efficiency of gene transfer. PMID:24904562

  9. The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster.

    PubMed

    Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly; Scott, Dana; Feldmann, Heinz

    2013-10-01

    Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster.

  10. Adaptive plasticity and epigenetic variation in response to warming in an Alpine plant

    PubMed Central

    Nicotra, Adrienne B; Segal, Deborah L; Hoyle, Gemma L; Schrey, Aaron W; Verhoeven, Koen J F; Richards, Christina L

    2015-01-01

    Environmentally induced phenotypic plasticity may be a critical component of response to changing environments. We examined local differentiation and adaptive phenotypic plasticity in response to elevated temperature in half-sib lines collected across an elevation gradient for the alpine herb, Wahlenbergia ceracea. Using Amplified Fragment Length Polymorphism (AFLP), we found low but significant genetic differentiation between low- and high-elevation seedlings, and seedlings originating from low elevations grew faster and showed stronger temperature responses (more plasticity) than those from medium and high elevations. Furthermore, plasticity was more often adaptive for plants of low-elevation origin and maladaptive for plants of high elevation. With methylation sensitive-AFLP (MS-AFLP), we revealed an increase in epigenetic variation in response to temperature in low-elevation seedlings. Although we did not find significant direct correlations between MS-AFLP loci and phenotypes, our results demonstrate that adaptive plasticity in temperature response to warming varies over fine spatial scales and suggest the involvement of epigenetic mechanisms in this response. PMID:25691987

  11. High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

    PubMed Central

    Martinez, N.; Michoud, G.; Cario, A.; Ollivier, J.; Franzetti, B.; Jebbar, M.; Oger, P.; Peters, J.

    2016-01-01

    Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure. PMID:27595789

  12. High protein flexibility and reduced hydration water dynamics are key pressure adaptive strategies in prokaryotes

    NASA Astrophysics Data System (ADS)

    Martinez, N.; Michoud, G.; Cario, A.; Ollivier, J.; Franzetti, B.; Jebbar, M.; Oger, P.; Peters, J.

    2016-09-01

    Water and protein dynamics on a nanometer scale were measured by quasi-elastic neutron scattering in the piezophile archaeon Thermococcus barophilus and the closely related pressure-sensitive Thermococcus kodakarensis, at 0.1 and 40 MPa. We show that cells of the pressure sensitive organism exhibit higher intrinsic stability. Both the hydration water dynamics and the fast protein and lipid dynamics are reduced under pressure. In contrast, the proteome of T. barophilus is more pressure sensitive than that of T. kodakarensis. The diffusion coefficient of hydration water is reduced, while the fast protein and lipid dynamics are slightly enhanced with increasing pressure. These findings show that the coupling between hydration water and cellular constituents might not be simply a master-slave relationship. We propose that the high flexibility of the T. barophilus proteome associated with reduced hydration water may be the keys to the molecular adaptation of the cells to high hydrostatic pressure.

  13. Defining the humoral immune response to infectious agents using high-density protein microarrays

    PubMed Central

    Vigil, Adam; Davies, D Huw; Felgner, Philip L

    2010-01-01

    A major component of the adaptive immune response to infection is the generation of protective and long-lasting humoral immunity. Traditional approaches to understanding the host’s humoral immune response are unable to provide an integrated understanding of the antibody repertoire generated in response to infection. By studying multiple antigenic responses in parallel, we can learn more about the breadth and dynamics of the antibody response to infection. Measurement of antibody production following vaccination is also a gauge for efficacy, as generation of antibodies can protect from future infections and limit disease. Protein microarrays are well suited to identify, quantify and compare individual antigenic responses following exposure to infectious agents. This technology can be applied to the development of improved serodiagnostic tests, discovery of subunit vaccine antigen candidates, epidemiologic research and vaccine development, as well as providing novel insights into infectious disease and the immune system. In this review, we will discuss the use of protein microarrays as a powerful tool to define the humoral immune response to bacteria and viruses. PMID:20143947

  14. Targeting unfolded protein response in cancer and diabetes.

    PubMed

    Mkrtchian, Souren

    2015-06-01

    The maturation of secretory and membrane proteins in the endoplasmic reticulum (ER) is tightly regulated by the unfolded protein response (UPR), a signal transduction pathway maintaining ER protein folding homeostasis. However, certain ER states are incompatible with cell survival and therefore the UPR may choose to eliminate severely disrupted cells by apoptosis. This is accomplished primarily through the activation of the transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP). In the April 2015 issue of Endocrine-Related Cancer, researchers from the universities of South Carolina and Athens (Greece) suggested a novel mechanism of CHOP-mediated apoptosis connected with the suppression of a prominent cell cycle regulator with anti-apoptotic activity, p21. These findings and suggested clinical applications, such as potentiation of cancer chemotherapy and a novel therapeutic approach for type 2 diabetes, are discussed in the context of UPR.

  15. Transcriptional Analysis of The Adaptive Digestive System of The Migratory Locust in Response to Plant Defensive Protease Inhibitors.

    PubMed

    Spit, Jornt; Holtof, Michiel; Badisco, Liesbet; Vergauwen, Lucia; Vogel, Elise; Knapen, Dries; Vanden Broeck, Jozef

    2016-09-01

    Herbivorous insects evolved adaptive mechanisms to compensate for the presence of plant defensive protease inhibitors (PI) in their food. The underlying regulatory mechanisms of these compensatory responses remain largely elusive. In the current study, we investigated the initiation of this adaptive response in the migratory locust, Locusta migratoria, via microarray analysis of gut tissues. Four hours after dietary uptake of PIs, 114 and 150 transcripts were respectively found up- or downregulated. The results suggest a quick trade-off between compensating for potential loss of digestive activity on the one hand, and stress tolerance, defense, and structural integrity of the gut on the other hand. We additionally addressed the role of a group of related upregulated hexamerin-like proteins in the PI-induced response. Simultaneous knockdown of corresponding transcripts by means of RNA interference resulted in a reduced capacity of the locust nymphs to cope with the effects of PI. Moreover, since insect hexamerins have been shown to bind Juvenile Hormone (JH), we also investigated the effect of JH on the proteolytic digestion in L. migratoria. Our results indicate that JH has a stimulatory effect on the expression of three homologous chymotrypsin genes, while knocking down the JH receptor (methoprene tolerant) led to opposite effects.

  16. Transcriptional Analysis of The Adaptive Digestive System of The Migratory Locust in Response to Plant Defensive Protease Inhibitors

    NASA Astrophysics Data System (ADS)

    Spit, Jornt; Holtof, Michiel; Badisco, Liesbet; Vergauwen, Lucia; Vogel, Elise; Knapen, Dries; vanden Broeck, Jozef

    2016-09-01

    Herbivorous insects evolved adaptive mechanisms to compensate for the presence of plant defensive protease inhibitors (PI) in their food. The underlying regulatory mechanisms of these compensatory responses remain largely elusive. In the current study, we investigated the initiation of this adaptive response in the migratory locust, Locusta migratoria, via microarray analysis of gut tissues. Four hours after dietary uptake of PIs, 114 and 150 transcripts were respectively found up- or downregulated. The results suggest a quick trade-off between compensating for potential loss of digestive activity on the one hand, and stress tolerance, defense, and structural integrity of the gut on the other hand. We additionally addressed the role of a group of related upregulated hexamerin-like proteins in the PI-induced response. Simultaneous knockdown of corresponding transcripts by means of RNA interference resulted in a reduced capacity of the locust nymphs to cope with the effects of PI. Moreover, since insect hexamerins have been shown to bind Juvenile Hormone (JH), we also investigated the effect of JH on the proteolytic digestion in L. migratoria. Our results indicate that JH has a stimulatory effect on the expression of three homologous chymotrypsin genes, while knocking down the JH receptor (methoprene tolerant) led to opposite effects.

  17. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory.

    PubMed

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A

    2009-04-15

    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  18. Transcriptional Analysis of The Adaptive Digestive System of The Migratory Locust in Response to Plant Defensive Protease Inhibitors

    PubMed Central

    Spit, Jornt; Holtof, Michiel; Badisco, Liesbet; Vergauwen, Lucia; Vogel, Elise; Knapen, Dries; Vanden Broeck, Jozef

    2016-01-01

    Herbivorous insects evolved adaptive mechanisms to compensate for the presence of plant defensive protease inhibitors (PI) in their food. The underlying regulatory mechanisms of these compensatory responses remain largely elusive. In the current study, we investigated the initiation of this adaptive response in the migratory locust, Locusta migratoria, via microarray analysis of gut tissues. Four hours after dietary uptake of PIs, 114 and 150 transcripts were respectively found up- or downregulated. The results suggest a quick trade-off between compensating for potential loss of digestive activity on the one hand, and stress tolerance, defense, and structural integrity of the gut on the other hand. We additionally addressed the role of a group of related upregulated hexamerin-like proteins in the PI-induced response. Simultaneous knockdown of corresponding transcripts by means of RNA interference resulted in a reduced capacity of the locust nymphs to cope with the effects of PI. Moreover, since insect hexamerins have been shown to bind Juvenile Hormone (JH), we also investigated the effect of JH on the proteolytic digestion in L. migratoria. Our results indicate that JH has a stimulatory effect on the expression of three homologous chymotrypsin genes, while knocking down the JH receptor (methoprene tolerant) led to opposite effects. PMID:27581362

  19. Analysis of the early adaptive response of endothelial cells to hypoxia via a long serial analysis of gene expression

    SciTech Connect

    Liang, Guang-Ping; Su, Yong-Yue; Chen, Jian; Yang, Zong-Cheng; Liu, You-Sheng; Luo, Xiang-Dong

    2009-07-10

    Activation of endothelial cells in humans is an early event in the response to hypoxia that may contribute to the endothelium's endogenous capacity to reduce tissue injury. To better understand the mechanism underlying this process, we utilized Long Serial Analysis of Gene Expression to study the transcriptome of human vein umbilical endothelial cells (EA.hy926) shortly after the induction of hypoxia. Of over 13,000 genes detected in each pool, 112 showed obvious differences in expression. Metabolic processes such as protein biosynthesis and proteolysis, aminoglycan metabolism, ribonucleotide biosynthesis, adenosine salvage, and lipid metabolism were reinforced. Pro-proliferation and pro-apoptotic states suggest the co-existence of pro- and anti-injury forces in endothelium shortly after the induction of hypoxia. Other adaptive responses include reinforced angiogenesis and vasodilation. Additionally, gene transcription in the endothelium shortly after the induction of hypoxia was regulated independently of HIF-1{alpha}. Our efforts to elucidate the adaptive response at an early post-hypoxia stage should contribute to further investigation of the protective processes that occur in the endothelium and has potential clinical implications.

  20. The unfolded protein response and translation attenuation: a modelling approach.

    PubMed

    Trusina, A; Tang, C

    2010-10-01

    Unfolded protein response (UPR) is a stress response to increased levels of unfolded proteins in the endoplasmic reticulum (ER). To deal with this stress, all eukaryotic cells share a well-conserved strategy--the upregulation of chaperons and proteases to facilitate protein folding and to degrade the misfolded proteins. For metazoans, however, an additional and seemingly redundant strategy has been evolved--translation attenuation (TA) of proteins targeted to the ER via the protein kinase PERK pathway. PERK is essential in secretory cells, such as the pancreatic β-cells, but not in non-secretory cell types. We have recently developed a mathematical model of UPR, focusing on the interplay and synergy between the TA arm and the conserved Ire1 arm of the UPR. The model showed that the TA mechanism is beneficial in highly fluctuating environment, for example, in the case where the ER stress changes frequently. Under highly variable levels of ER stress, tight regulation of the ER load by TA avoids excess amount of chaperons and proteases being produced. The model also showed that TA is of greater importance when there is a large flux of proteins through the ER. In this study, we further expand our model to investigate different types of ER stress and different temporal profiles of the stress. We found that TA is more desirable in dealing with the translation stress, for example, prolonged stimulation of proinsulin biosynthesis, than the chemical stress.

  1. Temperature adaptation at homologous sites in proteins from nine thermophile-mesophile species pairs.

    PubMed

    McDonald, John H

    2010-07-12

    Whether particular amino acids are favored by selection at high temperatures over others has long been an open question in protein evolution. One way to approach this question is to compare homologous sites in proteins from one thermophile and a closely related mesophile; asymmetrical substitution patterns have been taken as evidence for selection favoring certain amino acids over others. However, most pairs of prokaryotic species that differ in optimum temperature also differ in genome-wide GC content, and amino acid content is known to be associated with GC content. Here, I compare homologous sites in nine thermophilic prokaryotes and their mesophilic relatives, all with complete published genome sequences. After adjusting for the effects of differing GC content with logistic regression, 139 of the 190 pairs of amino acids show significant substitutional asymmetry, evidence of widespread adaptive amino acid substitution. The patterns are fairly consistent across the nine pairs of species (after taking the effects of differing GC content into account), suggesting that much of the asymmetry results from adaptation to temperature. Some amino acids in some species pairs deviate from the overall pattern in ways indicating that adaptation to other environmental or physiological differences between the species may also play a role. The property that is best correlated with the patterns of substitutional asymmetry is transfer free energy, a measure of hydrophobicity, with more hydrophobic amino acids favored at higher temperatures. The correlation of asymmetry and hydrophobicity is fairly weak, suggesting that other properties may also be important.

  2. THE UNFOLDED PROTEIN RESPONSE IN RELATION TO MITOCHONDRIAL BIOGENESIS IN SKELETAL MUSCLE CELLS.

    PubMed

    Mesbah Moosavi, Zahra S; Hood, David A

    2017-03-08

    Mitochondria are comprised of both nuclear- and mitochondrially-encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPR(ER)) or the mitochondrion (UPR(MT)) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown. Two models of mitochondrial biogenesis were used: muscle differentiation and chronic contractile activity (CCA) in murine muscle cells. After 4 days of differentiation, our findings depict selective activation of the UPR(MT) in which chaperones decreased, however Sirt3 and UPR(ER) markers were elevated. To delineate the role of ER stress in mitochondrial adaptations, the ER stress inhibitor TUDCA was administered. Surprisingly, mitochondrial markers COX-I, COX-IV, and PGC-1α protein levels were augmented up to 1.5-fold above that of vehicle-treated cells. Similar results were obtained in myotubes undergoing CCA in which biogenesis was enhanced by ~2-3-fold, along with elevated UPR(MT) markers Sirt3 and CPN10. To verify whether the findings were attributable to the terminal UPRER branch directed by the transcription factor CHOP, cells were transfected with CHOP siRNA. Basally, COX-I levels increased (~20%) and COX-IV decreased (~30%), suggesting that CHOP influences mitochondrial composition. This effect was fully restored by CCA. Therefore, our results suggest that mitochondrial biogenesis is independent of the terminal UPR(ER) Under basal conditions CHOP is required for the maintenance of mitochondrial composition, but not for differentiation- or CCA-induced mitochondrial biogenesis.

  3. Light adaptation increases response latency of alpha ganglion cells via a threshold-like nonlinearity.

    PubMed

    Chang, L; He, S

    2014-01-03

    Adaptation is an important process of sensory systems to adjust sensitivity to ensure the appropriate information encoding. Sensitivity and kinetics of retinal ganglion cell (RGC) responses have been studied extensively using a brief flash superimposed on different but steady backgrounds. However, it is still unclear if light adaptation exerts any effect on more complex response properties, such as response nonlinearity. In this study, we found that the latency of spike responses to a repeated flashing spot stimulation increased by 30 ms in the mouse ON α RGCs (An ON-type RGC is excited when a spot is turned on in the center of its receptive field). A single dimming event preceding the test flash on a steady adapting background could also produce similar effect in increasing latency of light responses. A simple computational model with a linear transformation of the light stimulus and a threshold-like nonlinearity could account for the experimental data. Moreover, the strength of the measured nonlinearity and the response latency were affected by the duration of light adaptation. The possible biological processes underlying this nonlinearity were explored. Voltage clamp recording revealed the presence of the increase in latency and threshold-like nonlinearity in the excitatory input of RGCs. However, no comparable nonlinearity was observed in the light responses of the ON cone bipolar cells. We further excluded GABAergic and glycinergic inhibition, N-methyl-D-aspartate receptor rectification and voltage-gated Na(+) channels as potential sources of this nonlinearity by pharmacological experiments. Our results indicate the bipolar cell terminals as the potential site of nonlinearity. Computational modeling constrained by experimental data supports that conclusion and suggests the voltage-sensitive Ca(++) channels and Ca(++)-dependent vesicle release in the bipolar cell terminals as mechanistic basis.

  4. Context-Specific Adaptation of Gravity-Dependent Vestibular Reflex Responses (NSBRI Neurovestibular Project 1)

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark; Goldberg, Jefim; Minor, Lloyd B.; Paloski, William H.; Young, Laurence R.; Zee, David S.

    1999-01-01

    Impairment of gaze and head stabilization reflexes can lead to disorientation and reduced performance in sensorimotor tasks such as piloting of spacecraft. Transitions between different gravitoinertial force (gif) environments - as during different phases of space flight - provide an extreme test of the adaptive capabilities of these mechanisms. We wish to determine to what extent the sensorimotor skills acquired in one gravity environment will transfer to others, and to what extent gravity serves as a context cue for inhibiting such transfer. We use the general approach of adapting a response (saccades, vestibuloocular reflex: VOR, or vestibulocollic reflex: VCR) to a particular change in gain or phase in one gif condition, adapting to a different gain or phase in a second gif condition, and then seeing if gif itself - the context cue - can recall the previously-learned adapted responses. Previous evidence indicates that unless there is specific training to induce context-specificity, reflex adaptation is sequential rather than simultaneous. Various experiments in this project investigate the behavioral properties, neurophysiological basis, and anatomical substrate of context-specific learning, using otolith (gravity) signals as a context cue. In the following, we outline the methods for all experiments in this project, and provide details and results on selected experiments.

  5. Global protein expression profile response of planktonic Aeromonas hydrophila exposed to chlortetracycline.

    PubMed

    Li, Wanxin; Yao, Zujie; Zhang, Xiangyu; Huang, Fang; Lin, Wenxiong; Lin, Xiangmin

    2017-04-01

    The antibiotics resistance phenomena of Aeromonas hydrophila has become serious economic and public health problems for the world aquaculture industry and human health care. In this study, to investigate the instinct antibiotics adaptive mechanism of this pathogen, iTRAQ (Isobaric Tags for Relative and Absolute Quantitation) based quantitative proteomics technologies were performed to compare the differential expression of A. hydrophila in planktonic status in response to chlortetracycline (CTC) stress and then identified total 1552 proteins including 285 altered proteins with 90 increasing and 195 decreasing abundance proteins. The following bioinformatics analysis showed that many metabolic metabolism pathways such as carbon metabolism, pyruvate metabolism, and glycolysis/gluconeogenesis were trend to down-regulated whereas β-Lactam resistance, RNA degradation, and amino acids biosynthesis processes were more likely to increase in CTC stress. The related pyruvate metabolism and β-Lactam resistance processes in mRNA level were further measured using the q-PCR method. Thus, an understanding of the behaviors of A. hydrophila in response to CTC would be helpful to reveal the antibiotics adaptive mechanism and for the development of novel antibiotics therapy.

  6. Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation Potentially Involved in the Adaptive Response of Cancer Cells to Oxygen-Deficient Conditions

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed with the aryl hydrocarbon receptor nuclear translocator, bind to and activate target genes as enhancers of transcription. In addition to this common mechanism, the induction of the unfolded protein response and mTOR signaling in response to endoplasmic reticulum stress is also known to be involved in the adaptation to hypoxia conditions. Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition to the well-characterized stress response mechanisms described above, increasing experimental evidence suggests that Sp1 and HIFs collaborate to drive gene expression in cancer cells in response to hypoxia, thereby regulating additional adaptive responses to cellular oxygen deficiency. However, these characteristics of Sp1 and their biological merits have not been summarized. In this review, we will discuss the diverse mechanisms of transcriptional regulation by Sp1 and their potential involvement in the adaptive response of cancer cells to hypoxic tumor microenvironments. PMID:26703734

  7. Substrate adaptabilities of Thermotogae mannan binding proteins as a function of their evolutionary histories.

    PubMed

    Boucher, Nathalie; Noll, Kenneth M

    2016-09-01

    The Thermotogae possess a large number of ATP-binding cassette (ABC) transporters, including two mannan binding proteins, ManD and CelE (previously called ManE). We show that a gene encoding an ancestor of these was acquired by the Thermotogae from the archaea followed by gene duplication. To address the functional evolution of these proteins as a consequence of their evolutionary histories, we measured the binding affinities of ManD and CelE orthologs from representative Thermotogae. Both proteins bind cellobiose, cellotriose, cellotetraose, β-1,4-mannotriose, and β-1,4-mannotetraose. The CelE orthologs additionally bind β-1,4-mannobiose, laminaribiose, laminaritriose and sophorose while the ManD orthologs additionally only weakly bind β-1,4-mannobiose. The CelE orthologs have higher unfolding temperatures than the ManD orthologs. An examination of codon sites under positive selection revealed that many of these encode residues located near or in the binding site, suggesting that the proteins experienced selective pressures in regions that might have changed their functions. The gene arrangement, phylogeny, binding properties, and putative regulatory networks suggest that the ancestral mannan binding protein was a CelE ortholog which gave rise to the ManD orthologs. This study provides a window on how one class of proteins adapted to new functions and temperatures to fit the physiologies of their new hosts.

  8. Massively parallel sampling of lattice proteins reveals foundations of thermal adaptation

    NASA Astrophysics Data System (ADS)

    Venev, Sergey V.; Zeldovich, Konstantin B.

    2015-08-01

    Evolution of proteins in bacteria and archaea living in different conditions leads to significant correlations between amino acid usage and environmental temperature. The origins of these correlations are poorly understood, and an important question of protein theory, physics-based prediction of types of amino acids overrepresented in highly thermostable proteins, remains largely unsolved. Here, we extend the random energy model of protein folding by weighting the interaction energies of amino acids by their frequencies in protein sequences and predict the energy gap of proteins designed to fold well at elevated temperatures. To test the model, we present a novel scalable algorithm for simultaneous energy calculation for many sequences in many structures, targeting massively parallel computing architectures such as graphics processing unit. The energy calculation is performed by multiplying two matrices, one representing the complete set of sequences, and the other describing the contact maps of all structural templates. An implementation of the algorithm for the CUDA platform is available at http://www.github.com/kzeldovich/galeprot and calculates protein folding energies over 250 times faster than a single central processing unit. Analysis of amino acid usage in 64-mer cubic lattice proteins designed to fold well at different temperatures demonstrates an excellent agreement between theoretical and simulated values of energy gap. The theoretical predictions of temperature trends of amino acid frequencies are significantly correlated with bioinformatics data on 191 bacteria and archaea, and highlight protein folding constraints as a fundamental selection pressure during thermal adaptation in biological evolution.

  9. Degree of adaptive response in urban tolerant birds shows influence of habitat-of-origin

    PubMed Central

    2014-01-01

    Urban exploiters and adapters are often coalesced under a term of convenience as ‘urban tolerant’. This useful but simplistic characterisation masks a more nuanced interplay between and within assemblages of birds that are more or less well adapted to a range of urban habitats. I test the hypotheses that objectively-defined urban exploiter and suburban adapter assemblages within the broad urban tolerant grouping in Melbourne vary in their responses within the larger group to predictor variables, and that the most explanatory predictor variables vary between the two assemblages. A paired, partitioned analysis of exploiter and adapter preferences for points along the urban–rural gradient was undertaken to decompose the overall trend into diagnosable parts for each assemblage. In a similar way to that in which time since establishment has been found to be related to high urban densities of some bird species and biogeographic origin predictive of urban adaptation extent, habitat origins of members of bird assemblages influence the degree to which they become urban tolerant. Bird species that objectively classify as urban tolerant will further classify as either exploiters or adapters according to the degree of openness of their habitats-of-origin. PMID:24688881

  10. Identification of Differentially Expressed Proteins and Phosphorylated Proteins in Rice Seedlings in Response to Strigolactone Treatment

    PubMed Central

    Chen, Fangyu; Jiang, Liangrong; Zheng, Jingsheng; Huang, Rongyu; Wang, Houcong; Hong, Zonglie; Huang, Yumin

    2014-01-01

    Strigolactones (SLs) are recently identified plant hormones that inhibit shoot branching and control various aspects of plant growth, development and interaction with parasites. Previous studies have shown that plant D10 protein is a carotenoid cleavage dioxygenase that functions in SL biosynthesis. In this work, we used an allelic SL-deficient d10 mutant XJC of rice (Oryza sativa L. spp. indica) to investigate proteins that were responsive to SL treatment. When grown in darkness, d10 mutant seedlings exhibited elongated mesocotyl that could be rescued by exogenous application of SLs. Soluble protein extracts were prepared from d10 mutant seedlings grown in darkness in the presence of GR24, a synthetic SL analog. Soluble proteins were separated on two-dimensional gels and subjected to proteomic analysis. Proteins that were expressed differentially and phosphoproteins whose phosphorylation status changed in response to GR24 treatment were identified. Eight proteins were found to be induced or down-regulated by GR24, and a different set of 8 phosphoproteins were shown to change their phosphorylation intensities in the dark-grown d10 seedlings in response to GR24 treatment. Analysis of these proteins revealed that they are important enzymes of the carbohydrate and amino acid metabolic pathways and key components of the cellular energy generation machinery. These proteins may represent potential targets of the SL signaling pathway. This study provides new insight into the complex and negative regulatory mechanism by which SLs control shoot branching and plant development. PMID:24699514

  11. Mineral proximity influences mechanical response of proteins in biological mineral-protein hybrid systems.

    PubMed

    Ghosh, Pijush; Katti, Dinesh R; Katti, Kalpana S

    2007-03-01

    The organic phase of nacre, which is composed primarily of proteins, has an extremely high elastic modulus as compared to that of bulk proteins, and also undergoes large deformation before failure. One reason for this unusually high modulus could be the mineral-organic interactions. In this work, we elucidate the specific role of mineral proximity on the structural response of proteins in biological structural composites such as nacre through molecular modeling. The "glycine-serine" domain of a nacre protein Lustrin A has been used as a model system. It is found that the amount of work needed to unfold is significantly higher when the GS domain is pulled in the proximity of aragonite. These results indicate that the proximity of aragonite has a significant effect on the unfolding mechanisms of proteins when pulled. These results will provide very useful information in designing synthetic biocomposites, as well as further our understanding of mechanical response in structural composites in nature.

  12. Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response

    PubMed Central

    Liliensiek, Birgit; Weigand, Markus A.; Bierhaus, Angelika; Nicklas, Werner; Kasper, Michael; Hofer, Stefan; Plachky, Jens; Gröne, Herman-Josef; Kurschus, Florian C.; Schmidt, Ann Marie; Yan, Shi Du; Martin, Eike; Schleicher, Erwin; Stern, David M.; Hämmerling, Günter J.; Nawroth, Peter P.; Arnold, Bernd

    2004-01-01

    While the initiation of the adaptive and innate immune response is well understood, less is known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these animal models RAGE does not play a role in the adaptive immune response. However, deletion of RAGE provides protection from the lethal effects of septic shock caused by cecal ligation and puncture. Such protection is reversed by reconstitution of RAGE in endothelial and hematopoietic cells. These results indicate that the innate immune response is controlled by pattern-recognition receptors not only at the initiating steps but also at the phase of perpetuation. PMID:15173891

  13. An adaptive two-stage dose-response design method for establishing Proof of Concept

    PubMed Central

    Franchetti, Yoko; Anderson, Stewart J.; Sampson, Allan R.

    2013-01-01

    We propose an adaptive two-stage dose-response design where a pre-specified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish ‘global’ PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs. PMID:23957520

  14. A cascade reaction network mimicking the basic functional steps of adaptive immune response

    NASA Astrophysics Data System (ADS)

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-10-01

    Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

  15. Adaptive urn designs for estimating several percentiles of a dose--response curve.

    PubMed

    Mugno, Raymond; Zhus, Wei; Rosenberger, William F

    2004-07-15

    Dose--response experiments are crucial in biomedical studies. There are usually multiple objectives in such experiments and among the goals is the estimation of several percentiles on the dose--response curve. Here we present the first non-parametric adaptive design approach to estimate several percentiles simultaneously via generalized Pólya urns. Theoretical properties of these designs are investigated and their performance is gaged by the locally compound optimal designs. As an example, we re-investigated a psychophysical experiment where one of the goals was to estimate the three quartiles. We show that these multiple-objective adaptive designs are more efficient than the original single-objective adaptive design targeting the median only. We also show that urn designs which target the optimal designs are slightly more efficient than those which target the desired percentiles directly. Guidelines are given as to when to use which type of design. Overall we are pleased with the efficiency results and hope compound adaptive designs proposed in this work or their variants may prove to be a viable non-parametric alternative in multiple-objective dose--response studies.

  16. Adaptive all the way down: building responsive materials from hierarchies of chemomechanical feedback.

    PubMed

    Grinthal, Alison; Aizenberg, Joanna

    2013-09-07

    A living organism is a bundle of dynamic, integrated adaptive processes: not only does it continuously respond to constant changes in temperature, sunlight, nutrients, and other features of its environment, but it does so by coordinating hierarchies of feedback among cells, tissues, organs, and networks all continuously adapting to each other. At the root of it all is one of the most fundamental adaptive processes: the constant tug of war between chemistry and mechanics that interweaves chemical signals with endless reconfigurations of macromolecules, fibers, meshworks, and membranes. In this tutorial we explore how such chemomechanical feedback - as an inherently dynamic, iterative process connecting size and time scales - can and has been similarly evoked in synthetic materials to produce a fascinating diversity of complex multiscale responsive behaviors. We discuss how chemical kinetics and architecture can be designed to generate stimulus-induced 3D spatiotemporal waves and topographic patterns within a single bulk material, and how feedback between interior dynamics and surface-wide instabilities can further generate higher order buckling and wrinkling patterns. Building on these phenomena, we show how yet higher levels of feedback and spatiotemporal complexity can be programmed into hybrid materials, and how these mechanisms allow hybrid materials to be further integrated into multicompartmental systems capable of hierarchical chemo-mechano-chemical feedback responses. These responses no doubt represent only a small sample of the chemomechanical feedback behaviors waiting to be discovered in synthetic materials, and enable us to envision nearly limitless possibilities for designing multiresponsive, multifunctional, self-adapting materials and systems.

  17. Context-Specific Adaptation of Gravity-Dependent Vestibular Reflex Responses

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark J.

    1999-01-01

    Stabilization of the eyes and head during body movements is important for maintaining balance and keeping the images of objects stationary on our retinas. Impairment of this ability can lead to disorientation and reduced performance in sensorimotor tasks such as piloting of spacecraft. In the absence of a normal earth gravity field, the dynamics of head stabilization, and the interpretation of vestibular signals that sense gravity and linear acceleration, are subject to change. Transitions between different gravitoinertial force environments - as during different phases of space flight - provide an extreme test of the adaptive mechanisms that maintain these reflexive abilities. It is vitally important to determine human adaptive capabilities in such a circumstance, so that we can know to what extent the sensorimotor skills acquired in one gravity environment will transfer to others. Our work lays the foundation for understanding these capabilities, and for determining how we can aid the processes of adaptation and readaptation. An integrated set of experiments addresses this issue. We use the general approach of adapting some type of reflexive eye movement (saccades, the angular vestibulo-ocular reflex (AVOR), the linear vestibulo-ocular reflex (LVOR)), or the vestibulo-collic reflex (VCR), to a particular change in gain or phase in one condition of gravitoiner-tial force, and adapting to a different gain or phase (or asking for no change) in a second gravitoinertial force condition, and then seeing if the gravitoinertial force itself - the context cue - can recall the previously learned adapted responses. The majority of the experiments in the laboratory use the direction of vertical gaze or the direction of gravity (head tilt) as the context cue. This allows us to study context-specificity in a ground-based setting. One set of experiments, to be performed in parabolic flight, specifically uses the magnitude of gravitoinertial force as a context cue. This is a

  18. Plasma amino acid response to graded levels of escape protein.

    PubMed

    Gibb, D J; Klopfenstein, T J; Britton, R A; Lewis, A J

    1992-09-01

    A trial was conducted to examine the potential of using plasma amino acid responses to graded levels of escape protein to determine limiting amino acids in cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet of corncob:sorghum silage (61:39) and were individually supplemented with distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50, 65, or 80% of the supplemental CP to come from distillers' protein and maintain an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73, or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at the 0% level to 17.3% at the 90% level. Plasma concentration of most essential plasma amino acids responded (P less than .10) linearly and(or) quadratically to increased escape protein. The broken-line response of plasma methionine at low DDG intake suggested that methionine was limiting at low levels of escape protein. An initial decrease followed by a plateau fit by a broken line indicated that histidine became limiting in FTH diets, and lysine eventually became limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached. Results indicate that plasma amino acid responses may identify amino acids that become limiting with increasing escape protein.

  19. Molecular adaptation and salt stress response of Halobacterium salinarum cells revealed by neutron spectroscopy.

    PubMed

    Vauclare, Pierre; Marty, Vincent; Fabiani, Elisa; Martinez, Nicolas; Jasnin, Marion; Gabel, Frank; Peters, Judith; Zaccai, Giuseppe; Franzetti, Bruno

    2015-11-01

    Halobacterium salinarum is an extreme halophile archaeon with an absolute requirement for a multimolar salt environment. It accumulates molar concentrations of KCl in the cytosol to counterbalance the external osmotic pressure imposed by the molar NaCl. As a consequence, cytosolic proteins are permanently exposed to low water activity and highly ionic conditions. In non-adapted systems, such conditions would promote protein aggregation, precipitation, and denaturation. In contrast, in vitro studies showed that proteins from extreme halophilic cells are themselves obligate halophiles. In this paper, adaptation via dynamics to low-salt stress in H. salinarum cells was measured by neutron scattering experiments coupled with microbiological characterization. The molecular dynamic properties of a proteome represent a good indicator for environmental adaptation and the neutron/microbiology approach has been shown to be well tailored to characterize these modifications. In their natural setting, halophilic organisms often have to face important variations in environmental salt concentration. The results showed deleterious effects already occur in the H. salinarum proteome, even when the external salt concentration is still relatively high, suggesting the onset of survival mechanisms quite early when the environmental salt concentration decreases.

  20. Adaptive changes in prey vulnerability shape the response of predator populations to mortality.

    PubMed

    Abrams, Peter A

    2009-11-21

    Simple models are used to explore how adaptive changes in prey vulnerability alter the population response of their predator to increased mortality. If the mortality is an imposed harvest, the change in prey vulnerability also influences the relationship between harvest effort and yield of the predator. The models assume that different prey phenotypes share a single resource, but have different vulnerabilities to the predator. Decreased vulnerability is assumed to decrease resource consumption rate. Adaptive change may occur by phenotypic changes in the traits of a single species or by shifts in the abundances of a pair of coexisting species or morphs. The response of the predator population is influenced by the shape of the predator's functional response, the shape of resource density dependence, and the shape of the tradeoff between vulnerability and food intake in the prey. Given a linear predator functional response, adaptive prey defense tends to produce a decelerating decline in predator population size with increased mortality. Prey defense may also greatly increase the range of mortality rates that allow predator persistence. If the predator has a type-2 response with a significant handling time, adaptive prey defense may have a greater variety of effects on the predator's response to mortality, sometimes producing alternative attractors, population cycles, or increased mean predator density. Situations in which there is disruptive selection on prey defense often imply a bimodal change in yield as a function of harvesting effort, with a minimum at intermediate effort. These results argue against using single-species models of density dependent growth to manage predatory species, and illustrate the importance of incorporating anti-predator behavior into models in applied population ecology.

  1. The Response of the Root Apex in Plant Adaptation to Iron Heterogeneity in Soil

    PubMed Central

    Li, Guangjie; Kronzucker, Herbert J.; Shi, Weiming

    2016-01-01

    Iron (Fe) is an essential micronutrient for plant growth and development, and is frequently limiting. By contrast, over-accumulation of Fe in plant tissues leads to toxicity. In soils, the distribution of Fe is highly heterogeneous. To cope with this heterogeneity, plant roots engage an array of adaptive responses to adjust their morphology and physiology. In this article, we review root morphological and physiological changes in response to low- and high-Fe conditions and highlight differences between these responses. We especially focus on the role of the root apex in dealing with the stresses resulting from Fe shortage and excess. PMID:27047521

  2. Mitogen-Activated Protein Kinase Hog1 Mediates Adaptation to G1 Checkpoint Arrest during Arsenite and Hyperosmotic Stress▿

    PubMed Central

    Migdal, Iwona; Ilina, Yulia; Tamás, Markus J.; Wysocki, Robert

    2008-01-01

    Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast (Saccharomyces cerevisiae) responds to osmotic stress by triggering G1 and G2 checkpoint delays that are dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high-osmolarity glycerol (HOG) pathway is also activated by arsenite, and the hog1Δ mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Δ cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G1 and G2 delays in wild-type cells, whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G1 cell cycle arrest. Elevated levels of intracellular arsenite and “cross talk” between the HOG and pheromone response pathways, observed in arsenite-treated hog1Δ cells, prolonged the G1 delay but did not cause a persistent G1 arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G1 exit in hog1Δ cells. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Δ cells. Interestingly, Sic1-dependent persistent G1 arrest was also observed in hog1Δ cells during hyperosmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G1 cell cycle arrest. PMID:18552285

  3. Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency.

    PubMed

    Zhang, Ji; Friedman, Morton H

    2013-09-15

    Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study (41), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 ± 15 dyn/cm(2) at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay.

  4. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men.

    PubMed

    McGinley, Cian; Bishop, David J

    2016-12-01

    McGinley C, Bishop DJ. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men. J Appl Physiol 121: 1290-1305, 2016. First published October 14, 2016; doi:10.1152/japplphysiol.00630.2016-This study measured the adaptive response to exercise training for each of the acid-base transport protein families, including providing isoform-specific evidence for the monocarboxylate transporter (MCT)1/4 chaperone protein basigin and for the electrogenic sodium-bicarbonate cotransporter (NBCe)1. We investigated whether 4 wk of work-matched, high-intensity interval training (HIIT), performed either just above the lactate threshold (HIITΔ20; n = 8), or close to peak aerobic power (HIITΔ90; n = 8), influenced adaptations in acid-base transport protein abundance, nonbicarbonate muscle buffer capacity (βmin vitro), and exercise capacity in active men. Training intensity did not discriminate between adaptations for most proteins measured, with abundance of MCT1, sodium/hydrogen exchanger (NHE) 1, NBCe1, carbonic anhydrase (CA) II, and CAXIV increasing after 4 wk, whereas there was little change in CAIII and CAIV abundance. βmin vitro also did not change. However, MCT4 protein content only increased for HIITΔ20 [effect size (ES): 1.06, 90% confidence limits × / ÷ 0.77], whereas basigin protein content only increased for HIITΔ90 (ES: 1.49, × / ÷ 1.42). Repeated-sprint ability (5 × 6-s sprints; 24 s passive rest) improved similarly for both groups. Power at the lactate threshold only improved for HIITΔ20 (ES: 0.49; 90% confidence limits ± 0.38), whereas peak O2 uptake did not change for either group. Detraining was characterized by the loss of adaptations for all of the proteins measured and for repeated-sprint ability 6 wk after removing the stimulus of HIIT. In conclusion, 4 wk of HIIT induced improvements in each of the acid-base transport protein families, but, remarkably, a 40

  5. Adaptation of aphid stylectomy for analyses of proteins and mRNAs in barley phloem sap.

    PubMed

    Gaupels, Frank; Buhtz, Anja; Knauer, Torsten; Deshmukh, Sachin; Waller, Frank; van Bel, Aart J E; Kogel, Karl-Heinz; Kehr, Julia

    2008-01-01

    Sieve tubes are transport conduits not only for photoassimilates but also for macromolecules and other compounds that are involved in sieve tube maintenance and systemic signalling. In order to gain sufficient amounts of pure phloem exudates from barley plants for analyses of the protein and mRNA composition, a previously described stylectomy set-up was optimized. Aphids were placed in sealed cages, which, immediately after microcauterization of the stylets, were flooded with water-saturated silicon oil. The exuding phloem sap was collected with a capillary connected to a pump. Using up to 30 plants and 600 aphids (Rhopalosiphum padi) in parallel, an average of 10 mul of phloem sap could be obtained within 6 h of sampling. In first analyses of the macromolecular content, eight so far unknown phloem mRNAs were identified by cDNA-amplified fragment length polymorphism. Transcripts in barley phloem exudates are related to metabolism, signalling, and pathogen defence, for example coding for a protein kinase and a pathogen- and insect-responsive WIR1A (wheat-induced resistance 1A)-like protein. Further, one-dimensional gel electrophoresis and subsequent partial sequencing by mass spectrometry led to the identification of seven major proteins with putative functions in stress responses and transport of mRNAs, proteins, and sugars. Two of the discovered proteins probably represent isoforms of a new phloem-mobile sucrose transporter. Notably, two-dimensional electrophoresis confirmed that there are >250 phloem proteins awaiting identification in future studies.

  6. A thermo-responsive protein treatment for dry eyes

    PubMed Central

    Wang, Wan; Jashnani, Aarti; Aluri, Suhaas R.; Gustafson, Joshua A.; Hsueh, Pang-Yu; Yarber, Frances; McKown, Robert L.; Laurie, Gordon W.; Hamm-Alvarez, Sarah F.; MacKay, J. Andrew

    2015-01-01

    Millions of Americans suffer from dry eye disease, and there are few effective therapies capable of treating these patients. A decade ago, an abundant protein component of human tears was discovered and named lacritin(Lacrt). Lacrt has prosecretory activity in the lacrimal gland and mitogenic activity at the corneal epithelium. Similar to other proteins placed on the ocular surface, the durability of its effect is limited by rapid tear turnover. Motivated by the rationale that a thermo-responsive coacervate containing Lacrt would have better retention upon administration, we have constructed and tested the activity of a thermo-responsive Lacrt fused to an Elastin-like polypeptide (ELP). Inspired from the human tropoelastin protein, ELP protein polymers reversibly phase separate into viscous coacervates above a tunable transition temperature. This fusion construct exhibited the prosecretory function of native Lacrt as illustrated by its ability to stimulate β-hexosaminidase secretion from primary rabbit lacrimal gland acinar cells. It also increased tear secretion from non-obese diabetic (NOD) mice, a model of autoimmune dacryoadenitis, when administered via intra-lacrimal injection. Lacrt ELP fusion proteins undergo temperature-mediated assembly to form a depot inside the lacrimal gland. We propose that these Lacrt ELP fusion proteins represent a potential therapy for dry eye disease and the strategy of ELP-mediated phase separation may have applicability to other diseases of the ocular surface. PMID:25481446

  7. Enzyme-Responsive Delivery of Multiple Proteins with Spatiotemporal Control

    PubMed Central

    Zhu, Suwei; Nih, Lina; Carmichael, S. Thomas; Lu, Yunfeng; Segura, Tatiana

    2015-01-01

    The growth of tissues and organs is regulated by orchestrated signals from biomolecules such as enzymes and growth factors. The ability to deliver signal molecules in response to particular biological events (e.g., enzyme expression and activation) holds great promise towards tissue healing and regeneration. The current delivery vehicles mainly rely on hydrolysable scaffolds and thin films of protein-containing polymers, which cannot be programmed to respond to biological signals. We report herein an injectable delivery platform based on enantiomeric protein nanocapsules, which can deliver multiple proteins with spatiotemporal control in response to the tissue proteases secreted during wound healing. Exemplified by stroke and diabetic wound healing in mice, sequential delivery of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) greatly enhances tissue revascularization and vessel maturation, providing effective delivery vehicles for tissue engineering and reparative medicine. PMID:25962336

  8. Multiscale biomechanical responses of adapted bone-periodontal ligament-tooth fibrous joints

    PubMed Central

    Jang, Andrew T.; Merkle, Arno; Fahey, Kevin; Gansky, Stuart A.; Ho, Sunita P.

    2015-01-01

    Reduced functional loads cause adaptations in organs. In this study, temporal adaptations of bone-ligament-tooth fibrous joints to reduced functional loads were mapped using a holistic approach. Systematic studies were performed to evaluate organ-level and tissue-level adaptations in specimens harvested periodically from rats given powder food for 6 months (N = 60 over 8,12,16,20, and 24 weeks). Bone-periodontal ligament (PDL)-tooth fibrous joint adaptation was evaluated by comparing changes in joint stiffness with changes in functional space between the tooth and alveolar bony socket. Adaptations in tissues included mapping changes in the PDL and bone architecture as observed from collagen birefringence, bone hardness and volume fraction in rats fed soft foods (soft diet, SD) compared to those fed hard pellets as a routine diet (hard diet, HD). In situ biomechanical testing on harvested fibrous joints revealed increased stiffness in SD groups (SD:239-605 N/mm) (p<0.05) at 8 and 12 weeks. Increased joint stiffness in early development phase was due to decreased functional space (at 8wks change in functional space was −33 µm, at 12wks change in functional space was −30 µm) and shifts in tissue quality as highlighted by birefringence, architecture and hardness. These physical changes were not observed in joints that were well into function, that is, in rodents older than 12 weeks of age. Significant adaptations in older groups were highlighted by shifts in bone growth (bone volume fraction 24wks: Δ-0.06) and bone hardness (8wks: Δ−0.04 GPa, 16 wks: Δ−0.07 GPa, 24wks: Δ−0.06 GPa). The response rate (N/s) of joints to mechanical loads decreased in SD groups. Results from the study showed that joint adaptation depended on age. The initial form-related adaptation (observed change in functional space) can challenge strain-adaptive nature of tissues to meet functional demands with increasing age into adulthood. The coupled effect between functional space in

  9. Water Demands with Two Adaptation Responses to Climate Change in a Mexican Irrigation District

    NASA Astrophysics Data System (ADS)

    Ojeda, W.; Iñiguez-Covarrubias, M.; Rojano, A.

    2012-12-01

    It is well documented that climate change is inevitable and that farmers need to adapt to changes in projected climate. Changes in water demands for a Mexican irrigation district were assessed using an irrigation scheduling model. The impact of two adaptations actions on water demands were estimated and compared with a baseline scenario. Wet and dry cropping plans were selected from the last 15 water years with actual climatology (1961-1990) taken as reference and three A1B climate change projection periods P1, P2 and P3 (2011-2040, 2041-2070, and 2071-2098). Projected precipitation and air temperature (medium, maximum and minimum) data were obtained through weighted averages of the best CGCM projections for Mexico, available at the IPCC data distribution center, using the Reliability Ensemble Averaging method (REA). Two adaptation farmers' responses were analyzed: use of longer season varieties and reduction of planting dates toward colder season as warming intensifies in the future. An annual accumulated ETo value of 1554 mm was estimated for the base period P0. Cumulative and Daily irrigations demands were generated for each agricultural season using the four climate projection series and considering adaptations actions. Figure 1 integrates in a unique net flow curve for the Fall-Winter season under selected adaptations actions. The simulation results indicated that for mid century (Period P2), the use of longer-season cultivars (AV) will have more pronounced effect in daily net flow based than the reduction of planting season (APS) as climate change intensifies during present century. Without adaptation (WA), the increase in temperature will shorten the growing season of all annual crops, generating a peak shift with respect to reference case (WA-P0). Combined adoptions of adaptation actions (AP+V) can generate higher, peak and cumulative, crop water requirements than actual values as Figure 1 shows. There are clear trends that without adaptations, water

  10. Multiscale biomechanical responses of adapted bone-periodontal ligament-tooth fibrous joints.

    PubMed

    Jang, Andrew T; Merkle, Arno P; Fahey, Kevin P; Gansky, Stuart A; Ho, Sunita P

    2015-12-01

    Reduced functional loads cause adaptations in organs. In this study, temporal adaptations of bone-ligament-tooth fibrous joints to reduced functional loads were mapped using a holistic approach. Systematic studies were performed to evaluate organ-level and tissue-level adaptations in specimens harvested periodically from rats (N=60) given powder food for 6 months over 8,12,16,20, and 24 weeks. Bone-periodontal ligament (PDL)-tooth fibrous joint adaptation was evaluated by comparing changes in joint stiffness with changes in functional space between the tooth and alveolar bony socket. Adaptations in tissues included mapping changes in the PDL and bone architecture as observed from collagen birefringence, bone hardness and volume fraction in rats fed soft foods (soft diet, SD) compared to those fed hard pellets as a routine diet (hard diet, HD). In situ biomechanical testing on harvested fibrous joints revealed increased stiffness in SD groups (SD:239-605 N/mm) (p<0.05) at 8 and 12 weeks. Increased joint stiffness in early development phase was due to decreased functional space (at 8 weeks change in functional space was -33 μm, at 12 weeks change in functional space was -30 μm) and shifts in tissue quality as highlighted by birefringence, architecture and hardness. These physical changes were not observed in joints that were well into function, that is, in rodents older than 12 weeks of age. Significant adaptations in older groups were highlighted by shifts in bone growth (bone volume fraction 24 weeks: Δ-0.06) and bone hardness (8 weeks: Δ-0.04 GPa, 16 weeks: Δ-0.07 GPa, 24 weeks: Δ-0.06 GPa). The response rate (N/s) of joints to mechanical loads decreased in SD groups. Results from the study showed that joint adaptation depended on age. The initial form-related adaptation (observed change in functional space) can challenge strain-adaptive nature of tissues to meet functional demands with increasing age into adulthood. The coupled effect between functional

  11. The unfolded protein response in immunity and inflammation

    PubMed Central

    Grootjans, Joep; Kaser, Arthur; Kaufman, Randal J.; Blumberg, Richard S.

    2017-01-01

    The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses. PMID:27346803

  12. The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 α-enhancer activity

    PubMed Central

    Kim, Yeha; Lim, Soyeon; Ha, Taejeong; Song, You-Hyang; Sohn, Young-In; Park, Dae-Jin; Paik, Sun-Sook; Kim-Kaneyama, Joo-ri; Song, Mi-Ryoung; Leung, Amanda; Levine, Edward M; Kim, In-Beom; Goo, Yong Sook; Lee, Seung-Hee; Kang, Kyung Hwa; Kim, Jin Woo

    2017-01-01

    The visual responses of vertebrates are sensitive to the overall composition of retinal interneurons including amacrine cells, which tune the activity of the retinal circuitry. The expression of Paired-homeobox 6 (PAX6) is regulated by multiple cis-DNA elements including the intronic α-enhancer, which is active in GABAergic amacrine cell subsets. Here, we report that the transforming growth factor ß1-induced transcript 1 protein (Tgfb1i1) interacts with the LIM domain transcription factors Lhx3 and Isl1 to inhibit the α-enhancer in the post-natal mouse retina. Tgfb1i1-/- mice show elevated α-enhancer activity leading to overproduction of Pax6ΔPD isoform that supports the GABAergic amacrine cell fate maintenance. Consequently, the Tgfb1i1-/- mouse retinas show a sustained light response, which becomes more transient in mice with the auto-stimulation-defective Pax6ΔPBS/ΔPBS mutation. Together, we show the antagonistic regulation of the α-enhancer activity by Pax6 and the LIM protein complex is necessary for the establishment of an inner retinal circuitry, which controls visual adaptation. DOI: http://dx.doi.org/10.7554/eLife.21303.001 PMID:28139974

  13. Sterol Regulatory Element Binding Protein (Srb1) Is Required for Hypoxic Adaptation and Virulence in the Dimorphic Fungus Histoplasma capsulatum

    PubMed Central

    DuBois, Juwen C.; Smulian, A. George

    2016-01-01

    The Histoplasma capsulatum sterol regulatory element binding protein (SREBP), Srb1 is a member of the basic helix-loop-helix (bHLH), leucine zipper DNA binding protein family of transcription factors that possess a unique tyrosine (Y) residue instead of an arginine (R) residue in the bHLH region. We have determined that Srb1 message levels increase in a time dependent manner during growth under oxygen deprivation (hypoxia). To further understand the role of Srb1 during infection and hypoxia, we silenced the gene encoding Srb1 using RNA interference (RNAi); characterized the resulting phenotype, determined its response to hypoxia, and its ability to cause disease within an infected host. Silencing of Srb1 resulted in a strain of H. capsulatum that is incapable of surviving in vitro hypoxia. We found that without complete Srb1 expression, H. capsulatum is killed by murine macrophages and avirulent in mice given a lethal dose of yeasts. Additionally, silencing Srb1 inhibited the hypoxic upregulation of other known H. capsulatum hypoxia-responsive genes (HRG), and genes that encode ergosterol biosynthetic enzymes. Consistent with these regulatory functions, Srb1 silenced H. capsulatum cells were hypersensitive to the antifungal azole drug itraconazole. These data support the theory that the H. capsulatum SREBP is critical for hypoxic adaptation and is required for H. capsulatum virulence. PMID:27711233

  14. The use of amphipols as universal molecular adapters to immobilize membrane proteins onto solid supports

    PubMed Central

    Charvolin, Delphine; Perez, Jean-Baptiste; Rouvière, Florent; Giusti, Fabrice; Bazzacco, Paola; Abdine, Alaa; Rappaport, Fabrice; Martinez, Karen L.; Popot, Jean-Luc

    2009-01-01

    Because of the importance of their physiological functions, cell membranes represent critical targets in biological research. Membrane proteins, which make up ≈1/3 of the proteome, interact with a wide range of small ligands and macromolecular partners as well as with foreign molecules such as synthetic drugs, antibodies, toxins, or surface recognition proteins of pathogenic organisms. Whether it is for the sake of basic biomedical or pharmacological research, it is of great interest to develop tools facilitating the study of these interactions. Surface-based in vitro assays are appealing because they require minimum quantities of reagents, and they are suitable for multiplexing and high-throughput screening. We introduce here a general method for immobilizing functional, unmodified integral membrane proteins onto solid supports, thanks to amphipathic polymers called “amphipols.” The key point of this approach is that functionalized amphipols can be used as universal adapters to associate any membrane protein to virtually any kind of support while stabilizing its native state. The generality and versatility of this strategy is demonstrated by using 5 different target proteins, 2 types of supports (chips and beads), 2 types of ligands (antibodies and a snake toxin), and 2 detection methods (surface plasmon resonance and fluorescence microscopy). PMID:19116278

  15. Temperature dependent mistranslation in a hyperthermophile adapts proteins to lower temperatures

    PubMed Central

    Schwartz, Michael H.; Pan, Tao

    2016-01-01

    All organisms universally encode, synthesize and utilize proteins that function optimally within a subset of growth conditions. While healthy cells are thought to maintain high translational fidelity within their natural habitats, natural environments can easily fluctuate outside the optimal functional range of genetically encoded proteins. The hyperthermophilic archaeon Aeropyrum pernix (A. pernix) can grow throughout temperature variations ranging from 70 to 100°C, although the specific factors facilitating such adaptability are unknown. Here, we show that A. pernix undergoes constitutive leucine to methionine mistranslation at low growth temperatures. Low-temperature mistranslation is facilitated by the misacylation of tRNALeu with methionine by the methionyl-tRNA synthetase (MetRS). At low growth temperatures, the A. pernix MetRS undergoes a temperature dependent shift in tRNA charging fidelity, allowing the enzyme to conditionally charge tRNALeu with methionine. We demonstrate enhanced low-temperature activity for A. pernix citrate synthase that is synthesized during leucine to methionine mistranslation at low-temperature growth compared to its high-fidelity counterpart synthesized at high-temperature. Our results show that conditional leucine to methionine mistranslation can make protein adjustments capable of improving the low-temperature activity of hyperthermophilic proteins, likely by facilitating the increasing flexibility required for greater protein function at lower physiological temperatures. PMID:26657639

  16. Increased rate of response of the pituitary-adrenal system in rats adapted to chronic stress

    NASA Technical Reports Server (NTRS)

    Sakellaris, P. C.; Vernikos-Danellis, J.

    1975-01-01

    The response and adaptation of the pituitary-adrenal system to chronic stresses was investigated. These included individual caging, confinement, and exposure to cold for varying periods of time. Studies were carried out demonstrating that during the period of adaptation when plasma corticosterone concentrations returned toward their prestress level despite continued exposure to the stressor, the animals responded to additional stimuli of ether for 1 min, a saline injection, or release from confinement with a faster increase (within 2.5 min) in plasma corticosterone than controls (10 min). It is concluded that during adaptation to a chronic stress the pituitary-adrenal system is not inhibited by the circulating steroid level but is actually hypersensitive to additional stimuli.

  17. Principles of exercise physiology: responses to acute exercise and long-term adaptations to training.

    PubMed

    Rivera-Brown, Anita M; Frontera, Walter R

    2012-11-01

    Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity.

  18. Genetic screening of new genes responsible for cellular adaptation to hypoxia using a genome-wide shRNA library.

    PubMed

    Yoshino, Seiko; Hara, Toshiro; Weng, Jane S; Takahashi, Yuka; Seiki, Motoharu; Sakamoto, Takeharu

    2012-01-01

    Oxygen is a vital requirement for multi-cellular organisms to generate energy and cells have developed multiple compensatory mechanisms to adapt to stressful hypoxic conditions. Such adaptive mechanisms are intricately interconnected with other signaling pathways that regulate cellular functions such as cell growth. However, our understanding of the overall system governing the cellular response to the availability of oxygen remains limited. To identify new genes involved in the response to hypoxic stress, we have performed a genome-wide gene knockdown analysis in human lung carcinoma PC8 cells using an shRNA library carried by a lentiviral vector. The knockdown analysis was performed under both normoxic and hypoxic conditions to identify shRNA sequences enriched or lost in the resulting selected cell populations. Consequently, we identified 56 candidate genes that might contribute to the cellular response to hypoxia. Subsequent individual knockdown of each gene demonstrated that 13 of these have a significant effect upon oxygen-sensitive cell growth. The identification of BCL2L1, which encodes a Bcl-2 family protein that plays a role in cell survival by preventing apoptosis, validates the successful design of our screen. The other selected genes have not previously been directly implicated in the cellular response to hypoxia. Interestingly, hypoxia did not directly enhance the expression of any of the identified genes, suggesting that we have identified a new class of genes that have been missed by conventional gene expression analyses to identify hypoxia response genes. Thus, our genetic screening method using a genome-wide shRNA library and the newly-identified genes represent useful tools to analyze the cellular systems that respond to hypoxic stress.

  19. Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune response in the central nervous system

    PubMed Central

    Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

    2009-01-01

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45highCD11b+) and CD8+ T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8+ T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo. PMID:19264338

  20. Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

    SciTech Connect

    Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

    2009-04-25

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45{sup high}CD11b{sup +}) and CD8{sup +} T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8{sup +} T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

  1. Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system.

    PubMed

    Steel, Christina D; Hahto, Suzanne M; Ciavarra, Richard P

    2009-04-25

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45(high)CD11b(+)) and CD8(+) T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8(+) T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

  2. Physiological Response to Membrane Protein Overexpression in E. coli*

    PubMed Central

    Gubellini, Francesca; Verdon, Grégory; Karpowich, Nathan K.; Luff, Jon D.; Boël, Grégory; Gauthier, Nils; Handelman, Samuel K.; Ades, Sarah E.; Hunt, John F.

    2011-01-01

    Overexpression represents a principal bottleneck in structural and functional studies of integral membrane proteins (IMPs). Although E. coli remains the leading organism for convenient and economical protein overexpression, many IMPs exhibit toxicity on induction in this host and give low yields of properly folded protein. Different mechanisms related to membrane biogenesis and IMP folding have been proposed to contribute to these problems, but there is limited understanding of the physical and physiological constraints on IMP overexpression and folding in vivo. Therefore, we used a variety of genetic, genomic, and microscopy techniques to characterize the physiological responses of Escherichia coli MG1655 cells to overexpression of a set of soluble proteins and IMPs, including constructs exhibiting different levels of toxicity and producing different levels of properly folded versus misfolded product on induction. Genetic marker studies coupled with transcriptomic results indicate only minor perturbations in many of the physiological systems implicated in previous studies of IMP biogenesis. Overexpression of either IMPs or soluble proteins tends to block execution of the standard stationary-phase transcriptional program, although these effects are consistently stronger for the IMPs included in our study. However, these perturbations are not an impediment to successful protein overexpression. We present evidence that, at least for the target proteins included in our study, there is no inherent obstacle to IMP overexpression in E. coli at moderate levels suitable for structural studies and that the biochemical and conformational properties of the proteins themselves are the major obstacles to success. Toxicity associated with target protein activity produces selective pressure leading to preferential growth of cells harboring expression-reducing and inactivating mutations, which can produce chemical heterogeneity in the target protein population, potentially

  3. Rapid Evolution of Coral Proteins Responsible for Interaction with the Environment

    SciTech Connect

    Voolstra, Christian R.; Sunagawa, Shinichi; Matz, Mikhail V.; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; DeSalvo, Michael K.; Lindquist, Erika; Szmant, Alina M.; Coffroth, Mary Alice; Medina, Monica

    2011-01-31

    Background: Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. Methodology/Principal Findings: We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7percent of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineagespecific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. Conclusion/Relevance: This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals? evolutionary response to global climate change.

  4. Rapid Evolution of Coral Proteins Responsible for Interaction with the Environment

    PubMed Central

    Matz, Mikhail V.; Bayer, Till; Aranda, Manuel; Buschiazzo, Emmanuel; DeSalvo, Michael K.; Lindquist, Erika; Szmant, Alina M.; Coffroth, Mary Alice; Medina, Mónica

    2011-01-01

    Background Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. Methodology/Principal Findings We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. Conclusion/Relevance This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change. PMID:21633702

  5. Enhanced Sleep Is an Evolutionarily Adaptive Response to Starvation Stress in Drosophila.

    PubMed

    Slocumb, Melissa E; Regalado, Josue M; Yoshizawa, Masato; Neely, Greg G; Masek, Pavel; Gibbs, Allen G; Keene, Alex C

    2015-01-01

    Animals maximize fitness by modulating sleep and foraging strategies in response to changes in nutrient availability. Wild populations of the fruit fly, Drosophila melanogaster, display highly variable levels of starvation and desiccation resistance that differ in accordance with geographic location, nutrient availability, and evolutionary history. Further, flies potently modulate sleep in response to changes in food availability, and selection for starvation resistance enhances sleep, revealing strong genetic relationships between sleep and nutrient availability. To determine the genetic and evolutionary relationship between sleep and nutrient deprivation, we assessed sleep in flies selected for desiccation or starvation resistance. While starvation resistant flies have higher levels of triglycerides, desiccation resistant flies have enhanced glycogen stores, indicative of distinct physiological adaptations to food or water scarcity. Strikingly, selection for starvation resistance, but not desiccation resistance, leads to increased sleep, indicating that enhanced sleep is not a generalized consequence of higher energy stores. Thermotolerance is not altered in starvation or desiccation resistant flies, providing further evidence for context-specific adaptation to environmental stressors. F2 hybrid flies were generated by crossing starvation selected flies with desiccation selected flies, and the relationship between nutrient deprivation and sleep was examined. Hybrids exhibit a positive correlation between starvation resistance and sleep, while no interaction was detected between desiccation resistance and sleep, revealing that prolonged sleep provides an adaptive response to starvation stress. Therefore, these findings demonstrate context-specific