WorldWideScience

Sample records for chemotaxis gene cheb2

  1. tlpA gene expression is required for arginine and bicarbonate chemotaxis in Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Oscar A Cerda

    2011-01-01

    Full Text Available About half of the human population is infected with Helicobacter pylori, a bacterium causing gastritis, peptic ulcer and progression to gastric cancer. Chemotaxis and flagellar motility are required for colonization and persistence of H. pylori in the gastric mucus layer. It is not completely clear which chemical gradients are used by H. pylori to maintain its position. TlpA, a chemotaxis receptor for arginine/ bicarbonate, has been identified. This study aimed to find out whether tlpA gene expression is required for the chemotactic response to arginine/bicarbonate. Wild-type motile H. pylori ATCC 700392 and H. pylori ATCC 43504, a strain having an interrupted tlpA gene, were used. Also, a tlpA-knockout mutant of H. pylori 700392 (H. pylori 700-tlpA::cat was produced by homologous recombination. Expression of tlpA was assessed by a Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR assay. Chemotaxis was measured as a Relative Chemotaxis Response (RCR by a modified capillary assay. H. pylori 700392 presented chemotaxis to arginine and sodium bicarbonate. H. pylori 700-tlpA::cat showed neither tlpA gene expression nor chemotaxis towards arginine and bicarbonate. Besides confirming that TlpA is a chemotactic receptor for arginine/bicarbonate in H. pylori, this study showed that tlpA gene expression is required for arginine/bicarbonate chemotaxis.

  2. Transport genes and chemotaxis in Laribacter hongkongensis: a genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Lau Susanna KP

    2011-08-01

    Full Text Available Abstract Background Laribacter hongkongensis is a Gram-negative, sea gull-shaped rod associated with community-acquired gastroenteritis. The bacterium has been found in diverse freshwater environments including fish, frogs and drinking water reservoirs. Using the complete genome sequence data of L. hongkongensis, we performed a comprehensive analysis of putative transport-related genes and genes related to chemotaxis, motility and quorum sensing, which may help the bacterium adapt to the changing environments and combat harmful substances. Results A genome-wide analysis using Transport Classification Database TCDB, similarity and keyword searches revealed the presence of a large diversity of transporters (n = 457 and genes related to chemotaxis (n = 52 and flagellar biosynthesis (n = 40 in the L. hongkongensis genome. The transporters included those from all seven major transporter categories, which may allow the uptake of essential nutrients or ions, and extrusion of metabolic end products and hazardous substances. L. hongkongensis is unique among closely related members of Neisseriaceae family in possessing higher number of proteins related to transport of ammonium, urea and dicarboxylate, which may reflect the importance of nitrogen and dicarboxylate metabolism in this assacharolytic bacterium. Structural modeling of two C4-dicarboxylate transporters showed that they possessed similar structures to the determined structures of other DctP-TRAP transporters, with one having an unusual disulfide bond. Diverse mechanisms for iron transport, including hemin transporters for iron acquisition from host proteins, were also identified. In addition to the chemotaxis and flagella-related genes, the L. hongkongensis genome also contained two copies of qseB/qseC homologues of the AI-3 quorum sensing system. Conclusions The large number of diverse transporters and genes involved in chemotaxis, motility and quorum sensing suggested that the bacterium may

  3. DNA Microarray and Gene Ontology Enrichment Analysis Reveals That a Mutation in opsX Affects Virulence and Chemotaxis in Xanthomonas oryzae pv. oryzae

    Science.gov (United States)

    Kim, Hong-Il; Park, Young-Jin

    2016-01-01

    Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial leaf blight (BLB) in rice (Oryza sativa L.). In this study, we investigated the effect of a mutation in opsX (XOO1056), which encodes a saccharide biosynthesis regulatory protein, on the virulence and bacterial chemotaxis of Xoo. We performed DNA microarray analysis, which showed that 63 of 2,678 genes, including genes related to bacterial motility (flagellar and chemotaxis proteins) were significantly downregulated (<−2 log2 fold changes) by the mutation in opsX. Indeed, motility assays showed that the mutant strain was nonmotile on semisolid agar swarm plates. In addition, a mutant strain (opsX::Tn5) showed decreased virulence against the susceptible rice cultivar, IR24. Quantitative real-time RT-PCR reaction was performed to confirm the expression levels of these genes, including those related to flagella and chemotaxis, in the opsX mutant. Our findings revealed that mutation of opsX affects both virulence and bacterial motility. These results will help to improve our understanding of Xoo and provide insight into Xoo-rice interactions. PMID:27298594

  4. Metallothionein mediates leukocyte chemotaxis

    Directory of Open Access Journals (Sweden)

    Lynes Michael A

    2005-09-01

    Full Text Available Abstract Background Metallothionein (MT is a cysteine-rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines Ccl17 and Cx3cl1. Cysteine motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor. Results In the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis. Conclusion These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure.

  5. Chemotaxis signaling systems in model beneficial plant-bacteria associations.

    Science.gov (United States)

    Scharf, Birgit E; Hynes, Michael F; Alexandre, Gladys M

    2016-04-01

    Beneficial plant-microbe associations play critical roles in plant health. Bacterial chemotaxis provides a competitive advantage to motile flagellated bacteria in colonization of plant root surfaces, which is a prerequisite for the establishment of beneficial associations. Chemotaxis signaling enables motile soil bacteria to sense and respond to gradients of chemical compounds released by plant roots. This process allows bacteria to actively swim towards plant roots and is thus critical for competitive root surface colonization. The complete genome sequences of several plant-associated bacterial species indicate the presence of multiple chemotaxis systems and a large number of chemoreceptors. Further, most soil bacteria are motile and capable of chemotaxis, and chemotaxis-encoding genes are enriched in the bacteria found in the rhizosphere compared to the bulk soil. This review compares the architecture and diversity of chemotaxis signaling systems in model beneficial plant-associated bacteria and discusses their relevance to the rhizosphere lifestyle. While it is unclear how controlling chemotaxis via multiple parallel chemotaxis systems provides a competitive advantage to certain bacterial species, the presence of a larger number of chemoreceptors is likely to contribute to the ability of motile bacteria to survive in the soil and to compete for root surface colonization. PMID:26797793

  6. Coupled Oscillators with Chemotaxis

    CERN Document Server

    Sawai, S; Sawai, Satoshi; Aizawa, Yoji

    1998-01-01

    A simple coupled oscillator system with chemotaxis is introduced to study morphogenesis of cellular slime molds. The model successfuly explains the migration of pseudoplasmodium which has been experimentally predicted to be lead by cells with higher intrinsic frequencies. Results obtained predict that its velocity attains its maximum value in the interface region between total locking and partial locking and also suggest possible roles played by partial synchrony during multicellular development.

  7. COUPLED CHEMOTAXIS FLUID MODEL

    KAUST Repository

    LORZ, ALEXANDER

    2010-06-01

    We consider a model system for the collective behavior of oxygen-driven swimming bacteria in an aquatic fluid. In certain parameter regimes, such suspensions of bacteria feature large-scale convection patterns as a result of the hydrodynamic interaction between bacteria. The presented model consist of a parabolicparabolic chemotaxis system for the oxygen concentration and the bacteria density coupled to an incompressible Stokes equation for the fluid driven by a gravitational force of the heavier bacteria. We show local existence of weak solutions in a bounded domain in d, d = 2, 3 with no-flux boundary condition and in 2 in the case of inhomogeneous Dirichlet conditions for the oxygen. © 2010 World Scientific Publishing Company.

  8. Identification and Characterization of a Putative Chemotaxis Protein, CheY, from the Oral Pathogen Campylobacter rectus

    OpenAIRE

    LaGier, Michael J.; Bilokopytov, Ihor; Cockerill, Bradley; Threadgill, Deborah S.

    2014-01-01

    Campylobacter rectus is an understudied oral bacterium that contributes to periodontitis. Processes that contribute to the disease-causing capabilities of pathogens, such as chemotaxis, are largely unknown in C. rectus. The aim of this study was to better understand C. rectus chemotaxis, by examining the C. rectus genome for the presence of a cheY gene. CheY proteins play a part in chemotaxis by acting as two-component response regulators. Significantly, CheY proteins from several pathogens, ...

  9. Dictyostelium Chemotaxis studied with fluorescence fluctuation spectroscopy

    NARCIS (Netherlands)

    Ruchira, A.

    2005-01-01

    The movement of cells in the direction of a chemical gradient, also known as chemotaxis, is a vital biological process. During chemotaxis, minute extracellular signals are translated into complex cellular responses such as change in morphology and motility. To understand the chemotaxis mechanism at

  10. Maze-solving by chemotaxis

    Science.gov (United States)

    Reynolds, A. M.

    2010-06-01

    Here, we report on numerical simulations showing that chemotaxis will take a body through a maze via the shortest possible route to the source of a chemoattractant. This is a robust finding that does not depend on the geometrical makeup of the maze. The predictions are supported by recent experimental studies which have shown that by moving down gradients in pH , a droplet of organic solvent can find the shortest of multiple possible paths through a maze to an acid-soaked exit. They are also consistent with numerical and experimental evidence that plant-parasitic nematodes take the shortest route through the labyrinth of air-filled pores within soil to preferred host plants that produce volatile chemoattractants. The predictions support the view that maze-solving is a robust property of chemotaxis and is not specific to particular kinds of maze or to the fractal structure of air-filled channels within soils.

  11. Chemotaxis of large granular lymphocytes

    International Nuclear Information System (INIS)

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1+ cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML(3H)P, suggesting that LGL bear receptors for the chemotactic peptide

  12. Regulation by Light of Chemotaxis to Nitrite during the Sexual Life Cycle in Chlamydomonas reinhardtii

    OpenAIRE

    Elena Ermilova; Zhanneta Zalutskaya

    2014-01-01

    Nitrite plays an important role in the nitrogen metabolism of most cells, including Chlamydomonas reinhardtii. We have shown that vegetative cells of C. reinhardtii are attracted by nitrite. The Nia1nit2 mutant with defects in genes encoding the nitrate reductase and regulatory protein NIT2 respectively was found to exhibit normal chemotaxis to nitrite. The data suggest that chemotaxis events appear to be specific and independent of those involved in nitrate assimilation. Unlike vegetative ce...

  13. Neutrophil Chemotaxis Dysfunction in Human Periodontitis

    OpenAIRE

    Van Dyke, T. E.; Horoszewicz, H. U.; Cianciola, L. J.; Genco, R J

    1980-01-01

    Polymorphonuclear leukocyte (PMNL) chemotaxis studies of 32 patients with localized juvenile periodontitis (periodontosis or LJP), 10 adult patients with a history of LJP (post-LJP), 8 patients with generalized juvenile periodontitis (GJP), and 23 adults with moderate to severe periodontitis were performed: (i) to determine the prevalence of a PMNL chemotaxis defect in a large group of LJP patients; (ii) to study PMNL chemotaxis in patients with other forms of severe periodontal disease; and ...

  14. Chemotaxis of Azospirillum Species to Aromatic Compounds

    OpenAIRE

    Lopez-de-Victoria, Geralyne; Lovell, Charles R.

    1993-01-01

    Chemotaxis of Azospirillum lipoferum Sp 59b and Azospirillum brasilense Sp 7 and Sp CD to malate and to the aromatic substrates benzoate, protocatechuate, 4-hydroxybenzoate, and catechol was assayed by the capillary method and direct cell counts. A. lipoferum required induction by growth on 4-hydroxybenzoate for positive chemotaxis to this compound. Chemotaxis of Azospirillum spp. to all other substrates did not require induction. Maximum chemotactic responses for most aromatic compounds occu...

  15. motA基因在空肠弯曲菌致病性相关趋化和定植中的作用%Contribution of motA gene in pathogenesis-associated chemotaxis and colonization of Campylobacter jejuni

    Institute of Scientific and Technical Information of China (English)

    阮萍; 孙爱华; 赵欣; 严杰

    2010-01-01

    Objective To determine the role of flagellar motor protein MotA in the pathogenesisassociated chemotaxis and colonization of Campylobacter jejuni. Methods The motA gene as well as Kan~r gene and plus-motA gene segments for motA gene knock-out were amplified by PCR and the target amplification fragments were sequenced after cloning. A suicide plasmid(pBlueskrit-Ⅱ-SK~(motA-kan)) and a motA gene knock-out mutant (motA~-) were constructed based on homologious recombination. By using semisolid plate migration test, hard agar plus (HAP)-based chemotactic test towards sodium deoxycholate (SDC) in vitro, and jejunal colonization test in BALB/c-ByJ mice were performed to determine the differences of flagellar motility, chemotaxis towards SDC and colonization in murine jejunum between motA~- mutant and wild-type strain. Results The nucleotide and amino acid sequences of the cloned motA gene were 100% identical to the reported corresponding sequences. The results of PCR, sequencing and continuous passage culture in antibiotics-contained medium demonstrated that both suicide plasmid and motA~- mutant were successfully generated. The diameters of clonies on semisolid plate and 0.2 mol/L SDC-induced chemotactic tings in HAP as well as the bacterial numbers adhering to the surface of murine jejunal mucosa and in jejunal content of motA~- mutant were significantly less than those of wild-type strain(P<0.05). Conclusion A motA gene knock-out mutant of C. jejuni was successfully constructed in this study, motA is an essential gene for flagellax motility, pathogenesis-associated chemotaxis and colonization of C. jejuni.%目的 确定鞭毛马达蛋白(flagellar motor protein)MotA编码基因在空肠弯曲菌(Campylobacter jejuni)致病性相关趋化和定植中的作用.方法 采用PCR扩增motA基因以及用于motA基因敲除的Kan~r基因和plus-motA基因片段,目的扩增产物克隆后测序.根据同源重组原理,构建空肠弯曲菌NCTC11168株motA基因自杀质

  16. Role of fliY gene in pathogenicity-associated chemotaxis and colonization of Campylobacter jejuni%fliY基因在空肠弯曲菌致病性相关趋化和定植中的作用

    Institute of Scientific and Technical Information of China (English)

    楼宏强; 葛玉梅; 张金良; 严杰; 赵金方

    2013-01-01

    Objective; To construct a knockout fliY gene mutant strain of Campylobacter jejuni for determining the role of FliY protein in flagellar movement related to bacterial motility, chemotaxis and colonization. Methods; The plasmid pBluescript-Ⅱ-SK was used to construct the suicide plasmid; according to homologous exchange principle, the suicide plasmid was utilized to generate fliY gene knockout mutant(fliY) in Campylobacter jejuni strain NCTC11168. The fliY mutant strain was identified by PCR, sequencing and Western blotting. The chemotactic and colonizing abilities of fliY mutant were determined by colony migration test and bacterial chemotactic test in vitro, and colonization test in jejunum of mice. Results; The fliY- mutant strain showed a growth curve in medium similar to that of wild-type strain. PCR, sequencing and Western blotting assay confirmed that the fliY gene in fliY- mutant was deleted. Compared to the wild-type strain,the colonies of fliY- mutant on semisolid plate were much smaller(P <0. 05) ,the chemotactic ability of fliY mutant towards sodium deoxycholate and bovine bile was significantly attenuated ( P <0. 05 ) ,and the number of fliY mutant(CFU) in jejunal tissue specimens of the infected mice was significantly decreased(P <0.05). Conclusion; The function of C. jejuni fliY gene refers to controlling flagellar movement,which is involved in bacterial chemotaxis and colonization.%目的:构建空肠弯曲菌(Campylobacter jejuni)鞭毛马达开关蛋白FliY编码基因(fliY)敲除突变株,了解FliY蛋白控制细菌鞭毛运动的作用及其与细菌趋化和定植的关系.方法:采用pBluescript-Ⅱ-SK质粒构建用于敲除空肠弯曲菌NCTC11168株fliy基因的自杀质粒.根据同源交换原理,利用自杀质粒构建空肠弯曲菌fliY基因敲除突变株(fliY-).采用PCR、PCR产物测序与Western Blot,对fliY-突变株进行鉴定.采用体外菌落迁徙试验、细菌趋化试验以及小鼠空肠定植试验,检测fliY-突

  17. Bacterial strategies for chemotaxis response.

    Science.gov (United States)

    Celani, Antonio; Vergassola, Massimo

    2010-01-26

    Regular environmental conditions allow for the evolution of specifically adapted responses, whereas complex environments usually lead to conflicting requirements upon the organism's response. A relevant instance of these issues is bacterial chemotaxis, where the evolutionary and functional reasons for the experimentally observed response to chemoattractants remain a riddle. Sensing and motility requirements are in fact optimized by different responses, which strongly depend on the chemoattractant environmental profiles. It is not clear then how those conflicting requirements quantitatively combine and compromise in shaping the chemotaxis response. Here we show that the experimental bacterial response corresponds to the maximin strategy that ensures the highest minimum uptake of chemoattractants for any profile of concentration. We show that the maximin response is the unique one that always outcompetes motile but nonchemotactic bacteria. The maximin strategy is adapted to the variable environments experienced by bacteria, and we explicitly show its emergence in simulations of bacterial populations in a chemostat. Finally, we recast the contrast of evolution in regular vs. complex environments in terms of minimax vs. maximin game-theoretical strategies. Our results are generally relevant to biological optimization principles and provide a systematic possibility to get around the need to know precisely the statistics of environmental fluctuations. PMID:20080704

  18. Bacillus subtilis Hfq: A role in chemotaxis and motility

    Indian Academy of Sciences (India)

    CHANDRAKANT B JAGTAP; PRADEEP KUMAR; K KRISHNAMURTHY RAO

    2016-09-01

    Hfq is a global post-transcriptional regulator that modulates the translation and stability of target mRNAs and therebyregulates pleiotropic functions, such as growth, stress, virulence and motility, in many Gram-negative bacteria.However, comparatively little is known about the regulation and function(s) of Hfq in Gram-positive bacteria.Recently, in Bacillus subtilis, a role for Hfq in stationary phase survival has been suggested, although the possibilityof Hfq having an additional role(s) cannot be ruled out. In this study we show that an ortholog of Hfq in B. subtilis isregulated by the stress sigma factor, σB, in addition to the stationary phase sigma factor, σH. We further demonstratethat Hfq positively regulates the expression of flagellum and chemotaxis genes (fla/che) that control chemotaxis andmotility, thus assigning a new function for Hfq in B. subtilis.

  19. Strenuous physical exercise adversely affects monocyte chemotaxis

    DEFF Research Database (Denmark)

    Czepluch, Frauke S; Barres, Romain; Caidahl, Kenneth;

    2011-01-01

    Physical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating...... in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor...

  20. Fundamental constraints on the abundances of chemotaxis proteins

    CERN Document Server

    Bitbol, Anne-Florence

    2015-01-01

    Flagellated bacteria, such as Escherichia coli, perform directed motion in gradients of concentration of attractants and repellents in a process called chemotaxis. The E. coli chemotaxis signaling pathway is a model for signal transduction, but it has unique features. We demonstrate that the need for fast signaling necessitates high abundances of the proteins involved in this pathway. We show that further constraints on the abundances of chemotaxis proteins arise from the requirements of self-assembly, both of flagellar motors and of chemoreceptor arrays. All these constraints are specific to chemotaxis, and published data confirm that chemotaxis proteins tend to be more highly expressed than their homologs in other pathways. Employing a chemotaxis pathway model, we show that the gain of the pathway at the level of the response regulator CheY increases with overall chemotaxis protein abundances. This may explain why, at least in one E. coli strain, the abundance of all chemotaxis proteins is higher in media w...

  1. Intestinal invasion of Salmonella enterica serovar Typhimurium in the avian host is dose dependent and does not depend on motility and chemotaxis

    DEFF Research Database (Denmark)

    Olsen, John Elmerdahl; Hoegh-Andersen, Kirsten Hobolt; Rosenkrantz, Jesper Tjørnholt;

    2013-01-01

    Salmonella enterica serotype Typhimurium (S. Typhimurium) can invade in the intestine of the avian host, and knowledge on the mechanisms that govern this is potentially important for prevention of disease. This study investigated the invasion of S. Typhimurium in the avian host and to which extent...... it depended on motility and chemotaxis.Wild type and previously well-characterized transposon mutants in flagella genes fliC and fljB and in chemotaxis genes cheA, cheB and cheR were used as challenge strains in intestinal loop experiments. Invasion was shown to be dose dependent, but did not require...... functional flagella or chemotaxis genes. In support of the results from intestinal loop experiments, flagella and chemotaxis genes were not significantly important to the outcome of an oral infection. The results showed that S. Typhimurium invasion in the avian host was dose dependent and was not affected by...

  2. Travelling Waves in Hybrid Chemotaxis Models

    KAUST Repository

    Franz, Benjamin

    2013-12-18

    Hybrid models of chemotaxis combine agent-based models of cells with partial differential equation models of extracellular chemical signals. In this paper, travelling wave properties of hybrid models of bacterial chemotaxis are investigated. Bacteria are modelled using an agent-based (individual-based) approach with internal dynamics describing signal transduction. In addition to the chemotactic behaviour of the bacteria, the individual-based model also includes cell proliferation and death. Cells consume the extracellular nutrient field (chemoattractant), which is modelled using a partial differential equation. Mesoscopic and macroscopic equations representing the behaviour of the hybrid model are derived and the existence of travelling wave solutions for these models is established. It is shown that cell proliferation is necessary for the existence of non-transient (stationary) travelling waves in hybrid models. Additionally, a numerical comparison between the wave speeds of the continuum models and the hybrid models shows good agreement in the case of weak chemotaxis and qualitative agreement for the strong chemotaxis case. In the case of slow cell adaptation, we detect oscillating behaviour of the wave, which cannot be explained by mean-field approximations. © 2013 Society for Mathematical Biology.

  3. Biomixing by chemotaxis and enhancement of biological reactions

    CERN Document Server

    Kiselev, Alexander

    2011-01-01

    Many processes in biology involve both reactions and chemotaxis. However, to the best of our knowledge, the question of interaction between chemotaxis and reactions has not yet been addressed either analytically or numerically. We consider a model with a single density function involving diffusion, advection, chemotaxis, and absorbing reaction. The model is motivated, in particular, by studies of coral broadcast spawning, where experimental observations of the efficiency of fertilization rates significantly exceed the data obtained from numerical models that do not take chemotaxis (attraction of sperm gametes by a chemical secreted by egg gametes) into account. We prove that in the framework of our model, chemotaxis plays a crucial role. There is a rigid limit to how much the fertilization efficiency can be enhanced if there is no chemotaxis but only advection and diffusion. On the other hand, when chemotaxis is present, the fertilization rate can be arbitrarily close to being complete provided that the chemo...

  4. Chemotaxis of crawling and swimming Caenorhabditis Elegans

    Science.gov (United States)

    Patel, Amar; Bilbao, Alejandro; Padmanabhan, Venkat; Khan, Zeina; Armstrong, Andrew; Rumbaugh, Kendra; Vanapalli, Siva; Blawzdziewicz, Jerzy

    2012-11-01

    A soil-dwelling nematode Caenorhabditis Elegans efficiently navigates through complex environments, responding to chemical signals to find food or avoid danger. According to previous studies, the nematode uses both gradual-turn and run-and-tumble strategies to move in the direction of the increasing concentration of chemical attractants. We show that both these chemotaxis strategies can be described using our kinematic model [PLoS ONE, 7: e40121 (2012)] in which harmonic-curvature modes represent elementary nematode movements. In our chemotaxis model, the statistics of mode changes is governed by the time history of the chemoattractant concentration at the position of the nematode head. We present results for both nematodes crawling without transverse slip and for swimming nematodes. This work was supported by NSF grant No. CBET 1059745.

  5. Chemotaxis: new role for Ras revealed

    Institute of Scientific and Technical Information of China (English)

    Jianshe Yan; Dale Hereld; Tian Jin

    2010-01-01

    @@ A recent study of chemotaxis revealed a new role for the proto-oncogene Ras in the social ameba Dictyostelium discoideum.Chemotaxis,the directional movement of cells toward chemokines and other chemoattractants,plays critical roles in diverse physiological processes,such as mobilization of immune cells to fight invading microorganisms,targeting of metastatic cancer cells to specific tissues,and guidance of sperm cells to ova during fertilization.This work,published in the July 26 issue of The Journal of Cell Biology,was conducted in Dr.Devreotes' lab at John Hopkins University and Dr.Parent's lab at National Cancer Institute.This research team demonstrated that RasC functions as an upstream regulator of TORC2 and thereby governs the effects of TORC2-PKB signaling on the cytoskeleton and cell migration.

  6. Travelling waves in hybrid chemotaxis models

    CERN Document Server

    Franz, Benjamin; Painter, Kevin J; Erban, Radek

    2013-01-01

    Hybrid models of chemotaxis combine agent-based models of cells with partial differential equation models of extracellular chemical signals. In this paper, travelling wave properties of hybrid models of bacterial chemotaxis are investigated. Bacteria are modelled using an agent-based (individual-based) approach with internal dynamics describing signal transduction. In addition to the chemotactic behaviour of the bacteria, the individual-based model also includes cell proliferation and death. Cells consume the extracellular nutrient field (chemoattractant) which is modelled using a partial differential equation. Mesoscopic and macroscopic equations representing the behaviour of the hybrid model are derived and the existence of travelling wave solutions for these models is established. It is shown that cell proliferation is necessary for the existence of non-transient (stationary) travelling waves in hybrid models. Additionally, a numerical comparison between the wave speeds of the continuum models and the hybr...

  7. Rho GTPases orient directional sensing in chemotaxis

    OpenAIRE

    Wang, Yu; Senoo, Hiroshi; Sesaki, Hiromi; Iijima, Miho

    2013-01-01

    During chemotaxis, cells recognize an extracellular chemical gradient and produce amplified intracellular responses independently of the actin cytoskeleton. This process is called directional sensing and observed as the activation of Ras GTPase and the production of phosphatidylinositol (3,4,5)-triphosphate (PIP3) toward higher concentrations of chemoattractants. How directional sensing is controlled is largely unknown. In our current study, we demonstrate that a Rho GTPase (RacE) and a Rho g...

  8. Modeling bacterial chemotaxis inside a cell

    OpenAIRE

    Ouannes, Nesrine; Djedi, Noureddine; Luga, Hervé; Duthen, Yves

    2014-01-01

    This paper describes a bacterial system that reproduces a population of bacteria that behave by simulating the internal reactions of each bacterial cell. The chemotaxis network of a cell is modulated by a hybrid approach that uses an algebraic model for the receptor clusters activity and an ordinary differential equation for the adaptation dynamics. The experiments are defined in order to simulate bacterial growth in an environment where nutrients are regularly added to it. The results show a...

  9. Imprecision of Adaptation in Escherichia coli Chemotaxis

    OpenAIRE

    Silke Neumann; Nikita Vladimirov; Krembel, Anna K.; Wingreen, Ned S.; Victor Sourjik

    2014-01-01

    Adaptability is an essential property of many sensory systems, enabling maintenance of a sensitive response over a range of background stimulus levels. In bacterial chemotaxis, adaptation to the preset level of pathway activity is achieved through an integral feedback mechanism based on activity-dependent methylation of chemoreceptors. It has been argued that this architecture ensures precise and robust adaptation regardless of the ambient ligand concentration, making perfect adaptation a cel...

  10. Methylation involved in chemotaxis is regulated during Caulobacter differentiation.

    OpenAIRE

    Shaw, P; Gomes, S L; Sweeney, K; Ely, B; L. Shapiro

    1983-01-01

    Caulobacter crescentus carries a flagellum and is motile only during a limited time in its cell cycle. We have asked if the biochemical machinery that mediates chemotaxis exists coincident with the cell's structural ability to respond to a chemotactic signal. We first demonstrated that one function of the chemotaxis machinery, the ability to methylate the carboxyl side chains of a specific set of membrane proteins (methyl-accepting chemotaxis proteins, MCPs), is present in C. crescentus. This...

  11. The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.

    Directory of Open Access Journals (Sweden)

    Tamding Wangdi

    2014-08-01

    Full Text Available Salmonella enterica serovar Typhi (S. Typhi causes typhoid fever, a disseminated infection, while the closely related pathogen S. enterica serovar Typhimurium (S. Typhimurium is associated with a localized gastroenteritis in humans. Here we investigated whether both pathogens differ in the chemotactic response they induce in neutrophils using a single-cell experimental approach. Surprisingly, neutrophils extended chemotactic pseudopodia toward Escherichia coli and S. Typhimurium, but not toward S. Typhi. Bacterial-guided chemotaxis was dependent on the presence of complement component 5a (C5a and C5a receptor (C5aR. Deletion of S. Typhi capsule biosynthesis genes markedly enhanced the chemotactic response of neutrophils in vitro. Furthermore, deletion of capsule biosynthesis genes heightened the association of S. Typhi with neutrophils in vivo through a C5aR-dependent mechanism. Collectively, these data suggest that expression of the virulence-associated (Vi capsular polysaccharide of S. Typhi obstructs bacterial-guided neutrophil chemotaxis.

  12. Self-similar dynamics of bacterial chemotaxis

    CERN Document Server

    Ngamsaad, Waipot

    2012-01-01

    We investigate the pattern formation of colony generated by chemotactic bacteria through a continuum model. In a simplified case, the dynamics of system is governed by a density-dependent convection-reaction-diffusion equation, $u_t = (u^{m})_{xx} - 2\\kappa(u^m)_{x}+ u - u^{m}$. This equation admits the analytical solutions that show the self-similarity of the bacterial colony's morphogenesis. In addition, we found that the colony evolves long time as the sharp traveling wave. The roles of chemotaxis on the regulation of pattern formation in these results are also discussed.

  13. Highlighting the role of Ras and Rap during Dictyostelium chemotaxis

    NARCIS (Netherlands)

    Kortholt, Arjan; van Haastert, Peter J. M.

    2008-01-01

    Chemotaxis, the directional movement towards a chemical compound, is an essential property of many cells and has been linked to the development and progression of many diseases. Eukaryotic chemotaxis is a complex process involving gradient sensing, cell polarity, remodelling of the cytoskeleton and

  14. Integration of chemotaxis, transport and catabolism in Pseudomonas putida and identification of the aromatic acid chemoreceptor PcaY.

    Science.gov (United States)

    Luu, Rita A; Kootstra, Joshua D; Nesteryuk, Vasyl; Brunton, Ceanne N; Parales, Juanito V; Ditty, Jayna L; Parales, Rebecca E

    2015-04-01

    Aromatic and hydroaromatic compounds that are metabolized through the β-ketoadipate catabolic pathway serve as chemoattractants for Pseudomonas putida F1. A screen of P. putida F1 mutants, each lacking one of the genes encoding the 18 putative methyl-accepting chemotaxis proteins (MCPs), revealed that pcaY encodes the MCP required for metabolism-independent chemotaxis to vanillate, vanillin, 4-hydroxybenzoate, benzoate, protocatechuate, quinate, shikimate, as well as 10 substituted benzoates that do not serve as growth substrates for P. putida F1. Chemotaxis was induced during growth on aromatic compounds, and an analysis of a pcaY-lacZ fusion revealed that pcaY is expressed in the presence of β-ketoadipate, a common intermediate in the pathway. pcaY expression also required the transcriptional activator PcaR, indicating that pcaY is a member of the pca regulon, which includes three unlinked gene clusters that encode five enzymes required for the conversion of 4-hydroxybenzoate to tricarboxylic acid cycle intermediates as well as the major facilitator superfamily transport protein PcaK. The 4-hydroxybenzoate permease PcaK was shown to modulate the chemotactic response by facilitating the uptake of 4-hydroxybenzoate, which leads to the accumulation of β-ketoadipate, thereby increasing pcaY expression. The results show that chemotaxis, transport and metabolism of aromatic compounds are intimately linked in P. putida. PMID:25582673

  15. A Sensitive Chemotaxis Assay Using a Novel Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Chen Zhang

    2013-01-01

    Full Text Available Existing chemotaxis assays do not generate stable chemotactic gradients and thus—over time—functionally measure only nonspecific random motion (chemokinesis. In comparison, microfluidic technology has the capacity to generate a tightly controlled microenvironment that can be stably maintained for extended periods of time and is, therefore, amenable to adaptation for assaying chemotaxis. We describe here a novel microfluidic device for sensitive assay of cellular migration and show its application for evaluating the chemotaxis of smooth muscle cells in a chemokine gradient.

  16. A coupled chemotaxis-fluid model: Global existence

    KAUST Repository

    Liu, Jian-Guo

    2011-09-01

    We consider a model arising from biology, consisting of chemotaxis equations coupled to viscous incompressible fluid equations through transport and external forcing. Global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the chemotaxis-Navier- Stokes system in two space dimensions, we obtain global existence for large data. In three space dimensions, we prove global existence of weak solutions for the chemotaxis-Stokes system with nonlinear diffusion for the cell density.© 2011 Elsevier Masson SAS. All rights reserved.

  17. Application of Coarse Integration to Bacterial Chemotaxis

    CERN Document Server

    Setayeshgar, S; Othmer, H G; Kevrekidis, Yu G

    2003-01-01

    We have developed and implemented a numerical evolution scheme for a class of stochastic problems in which the temporal evolution occurs on widely-separated time scales, and for which the slow evolution can be described in terms of a small number of moments of an underlying probability distribution. We demonstrate this method via a numerical simulation of chemotaxis in a population of motile, independent bacteria swimming in a prescribed gradient of a chemoattractant. The microscopic stochastic model, which is simulated using a Monte Carlo method, uses a simplified deterministic model for excitation/adaptation in signal transduction, coupled to a realistic, stochastic description of the flagellar motor. We show that projective time integration of ``coarse'' variables can be carried out on time scales long compared to that of the microscopic dynamics. Our coarse description is based on the spatial cell density distribution. Thus we are assuming that the system ``closes'' on this variable so that it can be desc...

  18. Chemotaxis of Azospirillum species to aromatic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-de-Victoria, G.; Lovell, C.R. (Univ. of South Carolina, Columbia, SC (United States))

    1993-09-01

    Azospirillum sspeciesare free-living nitrogen fixing bacteria commonly found in soils and in association with plant roots, including important agricultural crops. Rhizosphere colonization my Azospirillum species has been shown to stimulate growth of a variety of plant species. Chemotaxis is one of the properties which may contribute to survival, rhizosphere colonization and the initiation of mutualistic interactions by Azospirillum species. This study evaluates the chemotactic responses of three Azospirillum stains to a variety of aromatic compounds:benzoate, catechol, 4-HB, and PCA. Results indicate that the same aromatic substance can elicit different chemotactic responses from different Azospirillum species, and that Azospirillum can detect aromatic substrates at concentrations similar to those they encounter naturally. 36 refs., 1 fig., 6 tabs.

  19. An Improved Chamber for Direct Visualisation of Chemotaxis

    OpenAIRE

    Andrew J Muinonen-Martin; Douwe M Veltman; Gabriela Kalna; Insall, Robert H.

    2010-01-01

    There has been a growing appreciation over the last decade that chemotaxis plays an important role in cancer migration, invasion and metastasis. Research into the field of cancer cell chemotaxis is still in its infancy and traditional investigative tools have been developed with other cell types and purposes in mind. Direct visualisation chambers are considered the gold standard for investigating the behaviour of cells migrating in a chemotactic gradient. We therefore drew up a list of key at...

  20. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

    OpenAIRE

    Lee, W. L.; Shalita, A R; Suntharalingam, K; Fikrig, S M

    1982-01-01

    The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorph...

  1. An improved chamber for direct visualisation of chemotaxis.

    Directory of Open Access Journals (Sweden)

    Andrew J Muinonen-Martin

    Full Text Available There has been a growing appreciation over the last decade that chemotaxis plays an important role in cancer migration, invasion and metastasis. Research into the field of cancer cell chemotaxis is still in its infancy and traditional investigative tools have been developed with other cell types and purposes in mind. Direct visualisation chambers are considered the gold standard for investigating the behaviour of cells migrating in a chemotactic gradient. We therefore drew up a list of key attributes that a chemotaxis chamber should have for investigating cancer cell chemotaxis. These include (1 compatibility with thin cover slips for optimal optical properties and to allow use of high numerical aperture (NA oil immersion objectives; (2 gradients that are relatively stable for at least 24 hours due to the slow migration of cancer cells; (3 gradients of different steepnesses in a single experiment, with defined, consistent directions to avoid the need for complicated analysis; and (4 simple handling and disposability for use with medical samples. Here we describe and characterise the Insall chamber, a novel direct visualisation chamber. We use it to show GFP-lifeact transfected MV3 melanoma cells chemotaxing using a 60x high NA oil immersion objective, which cannot usually be done with other chemotaxis chambers. Linear gradients gave very efficient chemotaxis, contradicting earlier results suggesting that only polynomial gradients were effective. In conclusion, the chamber satisfies our design criteria, most importantly allowing high NA oil immersion microscopy to track chemotaxing cancer cells in detail over 24 hours.

  2. Bacterial Chemotaxis with a Moving Target

    Science.gov (United States)

    Dominick, Corey

    2015-03-01

    Most chemotaxis studies so far have been conducted in a quiescent fluid with a well-defined chemical gradient. Such experiments may be appropriate for studying enteric bacteria, such as Escherichia coli, but the environment it provides is very different from that typically encountered by marine bacteria. Herein we describe an experiment in which marine bacterium Vibrio alginolyticusis subject to stimulation by a small moving target. A micropipette of the tip size <1 ?m is used to slowly release a chemoattractant, serine, at different concentrations. The pipette is made to move with different patterns and speeds, ranging from 0 to 100 ?m/s; the latter is about twice the bacterial swimming speed. We found that if the pipette is moved slowly, with 1/4 of bacterial swimming speed, cells accumulate near the tip region but when it is moved with speed greater than 1/2 the bacterial swimming speed, cells trail behind the pipette over a large distance. The behaviors observed in V. alginolyticusare significantly different from E. coli, suggesting that the former is a better chemotaxer in a changing environment.

  3. Protein Connectivity in Chemotaxis Receptor Complexes.

    Directory of Open Access Journals (Sweden)

    Stephan Eismann

    2015-12-01

    Full Text Available The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

  4. External and internal constraints on eukaryotic chemotaxis.

    Science.gov (United States)

    Fuller, Danny; Chen, Wen; Adler, Micha; Groisman, Alex; Levine, Herbert; Rappel, Wouter-Jan; Loomis, William F

    2010-05-25

    Chemotaxis, the chemically guided movement of cells, plays an important role in several biological processes including cancer, wound healing, and embryogenesis. Chemotacting cells are able to sense shallow chemical gradients where the concentration of chemoattractant differs by only a few percent from one side of the cell to the other, over a wide range of local concentrations. Exactly what limits the chemotactic ability of these cells is presently unclear. Here we determine the chemotactic response of Dictyostelium cells to exponential gradients of varying steepness and local concentration of the chemoattractant cAMP. We find that the cells are sensitive to the steepness of the gradient as well as to the local concentration. Using information theory techniques, we derive a formula for the mutual information between the input gradient and the spatial distribution of bound receptors and also compute the mutual information between the input gradient and the motility direction in the experiments. A comparison between these quantities reveals that for shallow gradients, in which the concentration difference between the back and the front of a 10-mum-diameter cell is <5%, and for small local concentrations (<10 nM) the intracellular information loss is insignificant. Thus, external fluctuations due to the finite number of receptors dominate and limit the chemotactic response. For steeper gradients and higher local concentrations, the intracellular information processing is suboptimal and results in a smaller mutual information between the input gradient and the motility direction than would have been predicted from the ligand-receptor binding process. PMID:20457897

  5. Signal transduction and chemotaxis in mast cells.

    Science.gov (United States)

    Draber, Petr; Halova, Ivana; Polakovicova, Iva; Kawakami, Toshiaki

    2016-05-01

    Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis. PMID:25941081

  6. Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell chemotaxis

    Institute of Scientific and Technical Information of China (English)

    Ha-young LEE; Eun-ha SHIN; Yoe-sik BAE

    2006-01-01

    Aim: To investigate the effects of Sphingosylphosphorylcholine (SPC) on human monocyte-derived dendritic cell (DC) chemotaxis. Methods: Human DC were generated from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4. The effect of SPC on the DC chemotactic migration was measured by chemotaxis assay. Intracellular signaling event involved in the SPC-induced DC chemotaxis was investigated with several inhibitors for specific kinase. The expression of the SPC receptors was examined by reverse transcription polymerase chain reaction. Results: We found that SPC induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms of SPC-induced signaling events, mitogen activated protein kinase activation and Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3-kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do not express any of these receptors. To examine the involvement of sphin-gosine-1-phosphate (SIP) receptors, we checked the effect of an SIP receptor antagonist (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC chemotaxis. Conclusion: The results suggest that SPC may play a role in regulating DC trafficking during phagocytosis and the T cell-stimulating phase, and the unique SPC receptor, which is different from SIP receptors, is involved in SPC-induced chemotaxis.

  7. 幽门螺杆菌cheA基因在细菌体外趋化和体内定植过程中的作用%Role of Helicobacter pylori cheA gene in chemotaxis in vitro and colonizationin vivo

    Institute of Scientific and Technical Information of China (English)

    陈光; 严杰; 徐丽慧; 吴盛海; 王贤军

    2010-01-01

    Objective To determine the effect of cheA gene of Helicobacter pylori in the bacterial chemotaxis in vitro and colonization in vivo. Methods The entire cheA and cheY genes were amplified and cloned from genomic DNA of H. pylori NCTC11637 strain. Subsequently, the prokaryotic expression systems of cheA and cheY genes were generated and the target recombinant proteins rCheA and rCheY were extracted by Ni-NTA affinity chromatography. Rabbits were immunized with either rCheA or rCheY for obtaining antisera, and rCheA-IgG and rCheY-IgG in the antisera were prepared using ammonium sulfate precipitation plus DEAE-52 column chromatography. A suicide plasmid of cheA gene was constructed and then a cheA gene knock-out mutant ( cheA - ) was generated based on homologous recombinant exchange using the suicide plasmid. The cheA- mutant was identified using PCR and sequencing. The phosphorylation levels of CheA and CheY molecules of cheA - and wild-type strain were determined by using rCheA-IgG and rCheY-IgG anchoring the target proteins and protein phosphorylation detection kit. The differences of chemotaxis in vitro and colonization in vivo between cheA- mutant and wild-type strain were compared using chemotactic model and BALB/c infection model of H. pylori. Results The cheA gene knock-out in genome of cheA- mutant was confirmed by the results of PCR and sequencing. After treated with 0. 001-0. 1 mol/L HCI for 10 min, the phosphorylation levels of CheA and CheY molecules of wild-type strain were rapidly descended from ( 59.6 ±11.5) μmol and (55.5 ± 10.2) μmol to ( 10.8 ± 2.6) and (5. 5 ± 1.2) μmol (P < 0.05 ), while the phosphorylation of CheY molecule of cheA - mutant was no markedly changed with a persistent lower level ( P >0.05). The diameters [(10-20) ± (2-3) mm] of chemotactic aggregative rings of cheA- mutant were significantly less than those [(16-24) ± (2-3)mm] of wild-type strain (P <0.05). The positive isolation rate (90%) of H. pylori in gastric

  8. The sensory transduction pathways in bacterial chemotaxis

    Science.gov (United States)

    Taylor, Barry L.

    1989-01-01

    Bacterial chemotaxis is a useful model for investigating in molecular detail the behavioral response of cells to changes in their environment. Peritrichously flagellated bacteria such as coli and typhimurium swim by rotating helical flagella in a counterclockwise direction. If flagellar rotation is briefly reversed, the bacteria tumble and change the direction of swimming. The bacteria continuously sample the environment and use a temporal sensing mechanism to compare the present and immediate past environments. Bacteria respond to a broad range of stimuli including changes in temperature, oxygen concentration, pH and osmotic strength. Bacteria are attracted to potential sources of nutrition such as sugars and amino acids and are repelled by other chemicals. In the methylation-dependent pathways for sensory transduction and adaptation in E. coli and S. typhimurium, chemoeffectors bind to transducing proteins that span the plasma membrane. The transducing proteins are postulated to control the rate of autophosphorylation of the CheA protein, which in turn phosphorylates the CheY protein. The phospho-CheY protein binds to the switch on the flagellar motor and is the signal for clockwise rotation of the motor. Adaptation to an attractant is achieved by increasing methylation of the transducing protein until the attractant stimulus is cancelled. Responses to oxygen and certain sugars involve methylation-independent pathways in which adaption occurs without methylation of a transducing protein. Taxis toward oxygen is mediated by the electron transport system and changes in the proton motive force. Recent studies have shown that the methylation-independent pathway converges with the methylation-dependent pathway at or before the CheA protein.

  9. Chemotaxis on the Move – Active Learning Teaching Tool

    Directory of Open Access Journals (Sweden)

    Ann H. Williams

    2010-11-01

    Full Text Available In Microbiology courses, concepts such as chemotaxis can be difficult to visualize for students. Described here is a short visual playacting activity where students simulate E.coli moving towards an attractant source using a biased random walk. This short interactive activity is performed in the lecture course of General Microbiology that contains mostly Biology major juniors or seniors prior to the lecture on the subject of chemotaxis and flagellar movements. It is utilized to help students (class of 30–40 understand and visualize the process of chemotaxis and the concepts of random walk, biased random walk, runs, tumbles and directed movement of flagella in response to attractants and repellents.

  10. Single-cell twitching chemotaxis in developing biofilms.

    Science.gov (United States)

    Oliveira, Nuno M; Foster, Kevin R; Durham, William M

    2016-06-01

    Bacteria form surface-attached communities, known as biofilms, which are central to bacterial biology and how they affect us. Although surface-attached bacteria often experience strong chemical gradients, it remains unclear whether single cells can effectively perform chemotaxis on surfaces. Here we use microfluidic chemical gradients and massively parallel automated tracking to study the behavior of the pathogen Pseudomonas aeruginosa during early biofilm development. We show that individual cells can efficiently move toward chemoattractants using pili-based "twitching" motility and the Chp chemosensory system. Moreover, we discovered the behavioral mechanism underlying this surface chemotaxis: Cells reverse direction more frequently when moving away from chemoattractant sources. These corrective maneuvers are triggered rapidly, typically before a wayward cell has ventured a fraction of a micron. Our work shows that single bacteria can direct their motion with submicron precision and reveals the hidden potential for chemotaxis within bacterial biofilms. PMID:27222583

  11. DMPD: Cellular signaling in macrophage migration and chemotaxis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11073096 Cellular signaling in macrophage migration and chemotaxis. Jones GE. J Leu...koc Biol. 2000 Nov;68(5):593-602. (.png) (.svg) (.html) (.csml) Show Cellular signaling in macrophage migration... and chemotaxis. PubmedID 11073096 Title Cellular signaling in macrophage migration and chemotaxis. Autho

  12. Piracy on the molecular level: human herpesviruses manipulate cellular chemotaxis.

    Science.gov (United States)

    Cornaby, Caleb; Tanner, Anne; Stutz, Eric W; Poole, Brian D; Berges, Bradford K

    2016-03-01

    Cellular chemotaxis is important to tissue homeostasis and proper development. Human herpesvirus species influence cellular chemotaxis by regulating cellular chemokines and chemokine receptors. Herpesviruses also express various viral chemokines and chemokine receptors during infection. These changes to chemokine concentrations and receptor availability assist in the pathogenesis of herpesviruses and contribute to a variety of diseases and malignancies. By interfering with the positioning of host cells during herpesvirus infection, viral spread is assisted, latency can be established and the immune system is prevented from eradicating viral infection. PMID:26669819

  13. Chemotaxis plays multiple roles during Helicobacter pylori animal infection

    OpenAIRE

    Terry, K; S. M. Williams; Connolly, L.; Ottemann, K M

    2005-01-01

    Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as specific gastric cancers. H. pylori infects approximately 50% of the world's population, and infections can persist throughout the lifetime of the host. Motility and chemotaxis have been shown to be important in the infection process of H. pylori. We sought to address the specific roles of chemotaxis in infection of a mouse model system. We found that mutants lacking cheW, cheA, or cheY are ...

  14. Sperm chemotaxis promotes individual fertilization success in sea urchins.

    Science.gov (United States)

    Hussain, Yasmeen H; Guasto, Jeffrey S; Zimmer, Richard K; Stocker, Roman; Riffell, Jeffrey A

    2016-05-15

    Reproductive success fundamentally shapes an organism's ecology and evolution, and gamete traits mediate fertilization, which is a critical juncture in reproduction. Individual male fertilization success is dependent on the ability of sperm from one male to outcompete the sperm of other males when searching for a conspecific egg. Sperm chemotaxis, the ability of sperm to navigate towards eggs using chemical signals, has been studied for over a century, but such studies have long assumed that this phenomenon improves individual male fitness without explicit evidence to support this claim. Here, we assessed fertilization changes in the presence of a chemoattractant-digesting peptidase and used a microfluidic device coupled with a fertilization assay to determine the effect of sperm chemotaxis on individual male fertilization success in the sea urchin Lytechinus pictus We show that removing chemoattractant from the gametic environment decreases fertilization success. We further found that individual male differences in chemotaxis to a well-defined gradient of attractant correlate with individual male differences in fertilization success. These results demonstrate that sperm chemotaxis is an important contributor to individual reproductive success. PMID:26994183

  15. Evidence for bacterial chemotaxis to cyanobacteria from a radioassay technique

    International Nuclear Information System (INIS)

    Lyngbya birgei and Aphanizomenon flos-aquae elicited a significant chemotactic attraction of Aeromonas hydrophila compared with controls lacking cyanobacteria. There was a positive exponential relationship between biomass (chlorophyll a) of L. birgei and A. flos-aquae and chemotactic attraction of A. hydrophila. The assay equipment was simple and reliable and could be used to study bacterial chemotaxis in other species in situ

  16. Feedback control architecture and the bacterial chemotaxis network.

    Directory of Open Access Journals (Sweden)

    Abdullah Hamadeh

    2011-05-01

    Full Text Available Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance.

  17. Variation of chemosensory receptor content of Campylobacter jejuni strains and modulation of receptor gene expression under different in vivo and in vitro growth conditions

    OpenAIRE

    Day Christopher J; Hartley-Tassell Lauren E; Shewell Lucy K; King Rebecca M; Tram Greg; Day Serena K; Semchenko Evgeny A; Korolik Victoria

    2012-01-01

    Abstract Background Chemotaxis is crucial for the colonisation/infection of hosts with Campylobacter jejuni. Central to chemotaxis are the group A chemotaxis genes that are responsible for sensing the external environment. The distribution of group A chemoreceptor genes, as found in the C. jejuni sequenced strains, tlp1-4, 7, 10 and 11 were determined in 33 clinical human and avian isolates. Results Group A tlp gene content varied among the strains with genes encoding tlp1 (aspartate receptor...

  18. Feeding ducks, bacterial chemotaxis, and the Gini index

    CERN Document Server

    Peaudecerf, Francois J

    2015-01-01

    Classic experiments on the distribution of ducks around separated food sources found consistency with the `ideal free' distribution in which the local population is proportional to the local supply rate. Motivated by this experiment and others, we examine the analogous problem in the microbial world: the distribution of chemotactic bacteria around multiple nearby food sources. In contrast to the optimization of uptake rate that may hold at the level of a single cell in a spatially varying nutrient field, nutrient consumption by a population of chemotactic cells will modify the nutrient field, and the uptake rate will generally vary throughout the population. Through a simple model we study the distribution of resource uptake in the presence of chemotaxis, consumption, and diffusion of both bacteria and nutrients. Borrowing from the field of theoretical economics, we explore how the Gini index can be used as a means to quantify the inequalities of uptake. The redistributive effect of chemotaxis can lead to a p...

  19. Emergent collective chemotaxis without single-cell gradient sensing

    CERN Document Server

    Camley, Brian A; Levine, Herbert; Rappel, Wouter-Jan

    2015-01-01

    Many eukaryotic cells chemotax, sensing and following chemical gradients. However, even if single cells do not chemotax significantly, small clusters may still follow a gradient; this behavior is observed in neural crest cells and during border cell migration in Drosophila, but its origin remains puzzling. Here, we study this "collective guidance" analytically and computationally. We show collective chemotaxis can exist without single-cell chemotaxis if contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. We present explicit formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. Pairs of cells will have velocities that are strongly dependent on the cell pair's orientation: this provides a simple test for the presence of collective guidance in neural crest cells and other systems. We also study cluster-level adaptation, amplification, and cohesion via co-attraction.

  20. Global Solutions to the Coupled Chemotaxis-Fluid Equations

    KAUST Repository

    Duan, Renjun

    2010-08-10

    In this paper, we are concerned with a model arising from biology, which is a coupled system of the chemotaxis equations and the viscous incompressible fluid equations through transport and external forcing. The global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the Chemotaxis-Navier-Stokes system over three space dimensions, we obtain global existence and rates of convergence on classical solutions near constant states. When the fluid motion is described by the simpler Stokes equations, we prove global existence of weak solutions in two space dimensions for cell density with finite mass, first-order spatial moment and entropy provided that the external forcing is weak or the substrate concentration is small. © Taylor & Francis Group, LLC.

  1. On-Chip Open Microfluidic Devices for Chemotaxis Studies

    OpenAIRE

    Wright, Gus A.; Costa, Lino; Terekhov, Alexander; Jowhar, Dawit; Hofmeister, William; Janetopoulos, Christopher

    2012-01-01

    Microfluidic devices can provide unique control over both the chemoattractant gradient and the migration environment of the cells. Our work incorporates laser-machined micro and nanofluidic channels into bulk fused silica and cover slip-sized silica wafers. We have designed “open” chemotaxis devices that produce passive chemoattractant gradients without an external micropipette system. Since the migration area is unobstructed, cells can be easily loaded and strategically placed into the devic...

  2. Precision and Kinetics of Adaptation in Bacterial Chemotaxis

    OpenAIRE

    Meir, Yigal; Jakovljevic, Vladimir; Oleksiuk, Olga; Sourjik, Victor; Wingreen, Ned S.

    2010-01-01

    The chemotaxis network of the bacterium Escherichia coli is perhaps the most studied model for adaptation of a signaling system to persistent stimuli. Although adaptation in this system is generally considered to be precise, there has been little effort to quantify this precision, or to understand how and when precision fails. Using a Förster resonance energy transfer-based reporter of signaling activity, we undertook a systematic study of adaptation kinetics and precision in E. coli cells ex...

  3. The unique paradigm of spirochete motility and chemotaxis

    OpenAIRE

    Charon, Nyles W.; Cockburn, Andrew; Li, Chunhao; Liu, Jun; Miller, Kelly A.; MILLER, MICHAEL R.; Motaleb, Md.; Wolgemuth, Charles W.

    2012-01-01

    Spirochete motility is enigmatic: It differs from the motility of most other bacteria in that the entire bacterium is involved in translocation in the absence of external appendages. Using the Lyme disease spirochete Borrelia burgdorferi (Bb) as a model system, we explore the current research on spirochete motility and chemotaxis. Bb has periplasmic flagella (PFs) subterminally attached to each end of the protoplasmic cell cylinder, and surrounding the cell is an outer membrane. These interna...

  4. Characterizing asthma from a drop of blood using neutrophil chemotaxis.

    Science.gov (United States)

    Sackmann, Eric Karl-Heinz; Berthier, Erwin; Schwantes, Elizabeth A; Fichtinger, Paul S; Evans, Michael D; Dziadzio, Laura L; Huttenlocher, Anna; Mathur, Sameer K; Beebe, David J

    2014-04-22

    Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient's neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements. PMID:24711384

  5. Denitrification and chemotaxis of Pseudomonas stutzeri KC in porous media.

    Science.gov (United States)

    Roush, Caroline J; Lastoskie, Christian M; Worden, R Mark

    2006-01-01

    Chemotaxis is an important mechanism by which microorganisms are dispersed in porous media. A vigorous chemotactic response to concentration gradients formed by microbial consumption of chemoattractants can accelerate transport of bacteria to highly contaminated regions of soils and sediments, enhancing the efficiency of in situ bioremediation operations. Although chemotaxis plays a key role in establishment of biodegradation zones in the subsurface, the effects of physical heterogeneity on bacterial motility are poorly understood. To investigate the influence of porous media heterogeneity on microbial chemotaxis, swarm plate migration experiments were conducted using Pseudomonas stutzeri strain KC, a denitrifying bacterium used for in situ biodegradation of carbon tetrachloride in groundwater. Swarm plate measurements indicate that strain KC is strongly chemotactic toward both acetate and nitrate. A three-component mathematical model was developed to describe the migration of strain KC. Estimates of chemotactic sensitivity were obtained in the homogeneous (agar) phase and in a heterogeneous medium of aquifer solids extracted from the Schoolcraft bioremediation field site in western Michigan. Interestingly, the motility of strain KC is significantly larger in the porous medium than in the aqueous phase. We hypothesize that chemotactic response is enhanced within the heterogeneous medium because chemoattractant gradients formed by nitrate consumption are larger in the confined spaces of the porous medium than in unconfined agar solution. PMID:16760079

  6. iPLA2β: front and center in human monocyte chemotaxis to MCP-1

    OpenAIRE

    Mishra, Ravi S.; Carnevale, Kevin A.; Cathcart, Martha K.

    2008-01-01

    Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca2+-independent phospholipase (iPLA2β) and cytosolic phospholipase (cPLA2α), and subst...

  7. Perfect and near perfect adaptation in a model of bacterial chemotaxis

    OpenAIRE

    Mello, Bernardo A.; Tu, Yuhai

    2002-01-01

    The signaling apparatus mediating bacterial chemotaxis can adapt to a wide range of persistent external stimuli. In many cases, the bacterial activity returns to its pre-stimulus level exactly and this "perfect adaptability" is robust against variations in various chemotaxis protein concentrations. We model the bacterial chemotaxis signaling pathway, from ligand binding to CheY phosphorylation. By solving the steady-state equations of the model analytically, we derive a full set of conditions...

  8. Extracellular calmodulin regulates growth and cAMP-mediated chemotaxis in Dictyostelium discoideum

    Energy Technology Data Exchange (ETDEWEB)

    O' Day, Danton H., E-mail: danton.oday@utoronto.ca [Department of Cell and Systems Biology, University of Toronto, 25 Harbord St., Toronto, Ontario, Canada M5S 3G5 (Canada); Department of Biology, University of Toronto Mississauga, 3359 Mississauga Rd. N., Mississauga, Ontario, Canada L5L 1C6 (Canada); Huber, Robert J. [Department of Cell and Systems Biology, University of Toronto, 25 Harbord St., Toronto, Ontario, Canada M5S 3G5 (Canada); Suarez, Andres [Department of Biology, University of Toronto Mississauga, 3359 Mississauga Rd. N., Mississauga, Ontario, Canada L5L 1C6 (Canada)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Extracellular calmodulin is present throughout growth and development in Dictyostelium. Black-Right-Pointing-Pointer Extracellular calmodulin localizes within the ECM during development. Black-Right-Pointing-Pointer Extracellular calmodulin inhibits cell proliferation and increases chemotaxis. Black-Right-Pointing-Pointer Extracellular calmodulin exists in eukaryotic microbes. Black-Right-Pointing-Pointer Extracellular calmodulin may be functionally as important as intracellular calmodulin. -- Abstract: The existence of extracellular calmodulin (CaM) has had a long and controversial history. CaM is a ubiquitous calcium-binding protein that has been found in every eukaryotic cell system. Calcium-free apo-CaM and Ca{sup 2+}/CaM exert their effects by binding to and regulating the activity of CaM-binding proteins (CaMBPs). Most of the research done to date on CaM and its CaMBPs has focused on their intracellular functions. The presence of extracellular CaM is well established in a number of plants where it functions in proliferation, cell wall regeneration, gene regulation and germination. While CaM has been detected extracellularly in several animal species, including frog, rat, rabbit and human, its extracellular localization and functions are less well established. In contrast the study of extracellular CaM in eukaryotic microbes remains to be done. Here we show that CaM is constitutively expressed and secreted throughout asexual development in Dictyostelium where the presence of extracellular CaM dose-dependently inhibits cell proliferation but increases cAMP mediated chemotaxis. During development, extracellular CaM localizes within the slime sheath where it coexists with at least one CaMBP, the matricellular CaM-binding protein CyrA. Coupled with previous research, this work provides direct evidence for the existence of extracellular CaM in the Dictyostelium and provides insight into its functions in this model amoebozoan.

  9. FES kinase participates in KIT-ligand induced chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Voisset, Edwige, E-mail: Edwige.Voisset@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Lopez, Sophie, E-mail: Sophie.Lopez@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Chaix, Amandine, E-mail: Amandine.Chaix@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Vita, Marina, E-mail: Marina.Vita@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); George, Coralie, E-mail: Coralie.Georges@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); Dubreuil, Patrice, E-mail: Patrice.Dubreuil@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France); De Sepulveda, Paulo, E-mail: Sepulveda@inserm.fr [INSERM U891, Centre de Recherche en Cancerologie de Marseille (CRCM) (France); Institut Paoli-Calmettes, Marseille (France); Universite de la Mediterranee, Aix-Marseille II (France)

    2010-02-26

    FES is a cytoplasmic tyrosine kinase activated by several membrane receptors, originally identified as a viral oncogene product. We have recently identified FES as a crucial effector of oncogenic KIT mutant receptor. However, FES implication in wild-type KIT receptor function was not addressed. We report here that FES interacts with KIT and is phosphorylated following activation by its ligand SCF. Unlike in the context of oncogenic KIT mutant, FES is not involved in wild-type KIT proliferation signal, or in cell adhesion. Instead, FES is required for SCF-induced chemotaxis. In conclusion, FES kinase is a mediator of wild-type KIT signalling implicated in cell migration.

  10. Exact solutions of certain nonlinear chemotaxis diffusion reaction equations

    Indian Academy of Sciences (India)

    MISHRA AJAY; KAUSHAL R S; PRASAD AWADHESH

    2016-05-01

    Using the auxiliary equation method, we obtain exact solutions of certain nonlinear chemotaxis diffusion reaction equations in the presence of a stimulant. In particular, we account for the nonlinearities arising not only from the density-dependent source terms contributed by the particles and the stimulant but also from the coupling term of the stimulant. In addition to this, the diffusion of the stimulant and the effect of long-range interactions are also accounted for in theconstructed coupled differential equations. The results obtained here could be useful in the studies of several biological systems and processes, e.g., in bacterial infection, chemotherapy, etc.

  11. The Impact of Odor--Reward Memory on Chemotaxis in Larval "Drosophila"

    Science.gov (United States)

    Schleyer, Michael; Reid, Samuel F.; Pamir, Evren; Saumweber, Timo; Paisios, Emmanouil; Davies, Alexander; Gerber, Bertram; Louis, Matthieu

    2015-01-01

    How do animals adaptively integrate innate with learned behavioral tendencies? We tackle this question using chemotaxis as a paradigm. Chemotaxis in the "Drosophila" larva largely results from a sequence of runs and oriented turns. Thus, the larvae minimally need to determine (i) how fast to run, (ii) when to initiate a turn, and (iii)…

  12. A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst

    DEFF Research Database (Denmark)

    Royer, J F; Schratl, P; Lorenz, S;

    2007-01-01

    (2)-induced release of eosinophils from guinea pig bone marrow, and inhibited the chemotaxis of guinea pig bone marrow eosinophils and human peripheral blood eosinophils. Pretreatment with PGD(2) primed eosinophils for chemotaxis towards eotaxin, and this effect was prevented by Cay10471. In contrast...

  13. Inhibition of Escherichia coli chemotaxis by omega-conotoxin, a calcium ion channel blocker.

    OpenAIRE

    Tisa, L S; Olivera, B M; Adler, J

    1993-01-01

    Escherichia coli chemotaxis was inhibited by omega-conotoxin, a calcium ion channel blocker. With Tris-EDTA-permeabilized cells, nanomolar levels of omega-conotoxin inhibited chemotaxis without loss of motility. Cells treated with omega-conotoxin swam with a smooth bias, i.e., tumbling was inhibited.

  14. Normal chemotaxis in Dictyostelium discoideum cells with a depolarized plasma membrane potential

    NARCIS (Netherlands)

    Duijn, Bert van; Vogelzang, Sake A.; Ypey, Dirk L.; Molen, Loek G. van der; Haastert, Peter J.M. van

    1990-01-01

    We examined a possible role for the plasma membrane potential in signal transduction during cyclic AMP-induced chemotaxis in the cellular slime mold Dictyostelium discoideum. Chemotaxis, cyclic GMP and cyclic AMP responses in cells with a depolarized membrane potential were measured. Cells can be co

  15. Huntingtin regulates Ca(2+) chemotaxis and K(+)-facilitated cAMP chemotaxis, in conjunction with the monovalent cation/H(+) exchanger Nhe1, in a model developmental system: insights into its possible role in Huntington׳s disease.

    Science.gov (United States)

    Wessels, Deborah; Lusche, Daniel F; Scherer, Amanda; Kuhl, Spencer; Myre, Michael A; Soll, David R

    2014-10-01

    Huntington׳s disease is a neurodegenerative disorder, attributable to an expanded trinucleotide repeat in the coding region of the human HTT gene, which encodes the protein huntingtin. These mutations lead to huntingtin fragment inclusions in the striatum of the brain. However, the exact function of normal huntingtin and the defect causing the disease remain obscure. Because there are indications that huntingtin plays a role in Ca(2+) homeostasis, we studied the deletion mutant of the HTT ortholog in the model developmental system Dictyostelium discoideum, in which Ca(2+) plays a role in receptor-regulated behavior related to the aggregation process that leads to multicellular morphogenesis. The D. discoideum htt(-)-mutant failed to undergo both K(+)-facilitated chemotaxis in spatial gradients of the major chemoattractant cAMP, and chemotaxis up a spatial gradient of Ca(2+), but behaved normally in Ca(2+)-facilitated cAMP chemotaxis and Ca(2+)-dependent flow-directed motility. This was the same phenotypic profile of the null mutant of Nhel, a monovalent cation/H(+)exchanger. The htt(-)-mutant also failed to orient correctly during natural aggregation, as was the case for the Nhel mutant. Moreover, in a K(+)-based buffer the normal localization of actin was similarly defective in both htt(-) and nhe1(-) cells in a K(+)-based buffer, and the normal localization of Nhe1 was disrupted in the htt(-) mutant. These observations demonstrate that Htt and Nhel play roles in the same specific cation-facilitated behaviors and that Nhel localization is directly or indirectly regulated by Htt. Similar cation-dependent behaviors and a similar relationship between Htt and Nhe1 have not been reported for mammalian neurons and deserves investigation, especially as it may relate to Huntington׳s disease. PMID:25149514

  16. Biomixing by chemotaxis and efficiency of biological reactions: the critical reaction case

    CERN Document Server

    Kiselev, Alexander

    2012-01-01

    Many phenomena in biology involve both reactions and chemotaxis. These processes can clearly influence each other, and chemotaxis can play an important role in sustaining and speeding up the reaction. In continuation of our earlier work, we consider a model with a single density function involving diffusion, advection, chemotaxis, and absorbing reaction. The model is motivated, in particular, by the studies of coral broadcast spawning, where experimental observations of the efficiency of fertilization rates significantly exceed the data obtained from numerical models that do not take chemotaxis (attraction of sperm gametes by a chemical secreted by egg gametes) into account. We consider the case of the weakly coupled quadratic reaction term, which is the most natural from the biological point of view and was left open. The result is that similarly to higher power coupling, the chemotaxis plays a crucial role in ensuring efficiency of reaction. However, mathematically, the picture is quite different in the qua...

  17. Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

    DEFF Research Database (Denmark)

    Nielsen, H; Kharazmi, A; Theander, T G

    1986-01-01

    tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the...... suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No...... significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of...

  18. Noise-Induced Increase of Sensitivity in Bacterial Chemotaxis.

    Science.gov (United States)

    He, Rui; Zhang, Rongjing; Yuan, Junhua

    2016-07-26

    Flagellated bacteria, like Escherichia coli, can swim toward beneficial environments by modulating the rotational direction of their flagellar motors through a chemotaxis signal transduction network. The noise of this network, the random fluctuation of the intracellular concentration of the signal protein CheY-P with time, has been identified in studies of single cell behavioral variability, and found to be important in coordination of multiple motors in a bacterium and in enhancement of bacterial drift velocity in chemical gradients. Here, by comparing the behavioral difference between motors of wild-type E. coli and mutants without signal noise, we measured the magnitude of this noise in wild-type cells, and found that the noise increases the sensitivity of the bacterial chemotaxis network downstream at the level of the flagellar motor. This provided a simple mechanism for the noise-induced enhancement of chemotactic drift, which we confirmed by simulating the E. coli chemotactic motion in various spatial profiles of chemo-attractant concentration. PMID:27463144

  19. Feeding ducks, bacterial chemotaxis, and the Gini index

    Science.gov (United States)

    Peaudecerf, François J.; Goldstein, Raymond E.

    2015-08-01

    Classic experiments on the distribution of ducks around separated food sources found consistency with the "ideal free" distribution in which the local population is proportional to the local supply rate. Motivated by this experiment and others, we examine the analogous problem in the microbial world: the distribution of chemotactic bacteria around multiple nearby food sources. In contrast to the optimization of uptake rate that may hold at the level of a single cell in a spatially varying nutrient field, nutrient consumption by a population of chemotactic cells will modify the nutrient field, and the uptake rate will generally vary throughout the population. Through a simple model we study the distribution of resource uptake in the presence of chemotaxis, consumption, and diffusion of both bacteria and nutrients. Borrowing from the field of theoretical economics, we explore how the Gini index can be used as a means to quantify the inequalities of uptake. The redistributive effect of chemotaxis can lead to a phenomenon we term "chemotactic levelling," and the influence of these results on population fitness are briefly considered.

  20. The Effect Of Chemotaxis On The Swarming Ability Of Bacillus Subtilis Critical Effect Of Glutamic Acid And Lysine

    Directory of Open Access Journals (Sweden)

    Lina Hamouche

    2015-08-01

    Full Text Available Abstract Bacterial cells differentiation constitutes an appropriate and efficient way to respond to an ever-changing environment. Bacillus subtilis are no different where in some conditions planktonic cells differentiate into highly motile swarmer cells. The hyperflagellated swarmer cells located usually at the colony edge move in a cooperative manner in order to reconnoiter new sites for colonization this movement is called swarming. The chemotaxis proteins take a part of several factors playing an essential role in swarmer differentiation hence migration therefore we assumed a connection between chemotaxis and swarming profile of B. subtilis. To this end we examined the effect of amino acids chemoattractants glutamic acid and lysine deprivation on the capability of swarming. Here we show that deprivation of synthetic B-media from glutamic acid result on attenuated defective and random swarming pattern deprivation of lysine lead to an almost normal swarming pattern meanwhile double deprivation of both amino acids result in important reduction of swarming capability. Moreover we developed a method to screen the chemotaxis clearly using swarm plates with concentration gradient. Using this approach we found that B. subtilis manage to swarm completely toward glutamic acid and didnt swarm toward medium lacking this amino acid meanwhile the bacteria manage to swarm in all sides of plates with concentration gradient of lysine. Furthermore our results indicate that these two chemoattractants can reduce the motility by modulating the expression of hag gene. The absence of glutamic acid and lysine decrease the expression of hag during swarming respectively for 36 and 15.

  1. The domain dependence of chemotaxis in two-dimensional turbulence

    Science.gov (United States)

    Tang, Wenbo; Jones, Kimberly; Walker, Phillip

    2015-11-01

    Coherent structures are ubiquitous in environmental and geophysical flows and they affect reaction-diffusion processes in profound ways. In this presentation, we show an example of the domain dependence of chemotaxis process in a two-dimensional turbulent flow. The flow has coherent structures that form barriers that prohibit long-range transport of tracers. Accordingly, the uptake advantage of nutrient by motile and nonmotile species differs significantly if the process start in different locations of the flow. Interestingly, the conventional diagnostic of Finite-time Lyapunov exponents alone is not sufficient to explain the variability -- methods to extract elliptic transport barriers are essential to relate to the explanation. We also offer some explanations of the observed scalar behaviors via analyses of bulk quantities. Support: NSF-DMS-1212144.

  2. Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

    Directory of Open Access Journals (Sweden)

    Liptak Amy R

    2003-11-01

    Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

  3. Computational Chemotaxis in Ants and Bacteria over Dynamic Environments

    CERN Document Server

    Ramos, Vitorino; Rosa, A C; Abraham, A

    2007-01-01

    Chemotaxis can be defined as an innate behavioural response by an organism to a directional stimulus, in which bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food (e.g., glucose) by swimming towards the highest concentration of food molecules, or to flee from poisons. Based on self-organized computational approaches and similar stigmergic concepts we derive a novel swarm intelligent algorithm. What strikes from these observations is that both eusocial insects as ant colonies and bacteria have similar natural mechanisms based on stigmergy in order to emerge coherent and sophisticated patterns of global collective behaviour. Keeping in mind the above characteristics we will present a simple model to tackle the collective adaptation of a social swarm based on real ant colony behaviors (SSA algorithm) for tracking extrema in dynamic environments and highly multimodal complex functions des...

  4. Toward Synthetic Spatial Patterns in Engineered Cell Populations with Chemotaxis.

    Science.gov (United States)

    Duran-Nebreda, Salva; Solé, Ricard V

    2016-07-15

    A major force shaping form and patterns in biology is based in the presence of amplification mechanisms able to generate ordered, large-scale spatial structures out of local interactions and random initial conditions. Turing patterns are one of the best known candidates for such ordering dynamics, and their existence has been proven in both chemical and physical systems. Their relevance in biology, although strongly supported by indirect evidence, is still under discussion. Extensive modeling approaches have stemmed from Turing's pioneering ideas, but further confirmation from experimental biology is required. An alternative possibility is to engineer cells so that self-organized patterns emerge from local communication. Here we propose a potential synthetic design based on the interaction between population density and a diffusing signal, including also directed motion in the form of chemotaxis. The feasibility of engineering such a system and its implications for developmental biology are also assessed. PMID:27009520

  5. Singularity formation in chemotaxis systems with volume-filling effect

    International Nuclear Information System (INIS)

    A parabolic–elliptic model of chemotaxis which takes into account volume-filling effects is considered under the assumption that there is an a priori threshold for the cell density. For a wide range of nonlinear diffusion operators including singular and degenerate ones it is proved that if the taxis force is strong enough with respect to diffusion and the initial data are chosen properly then there exists a classical solution which reaches the threshold at the maximal time of its existence, no matter whether the latter is finite or infinite. Moreover, we prove that the threshold may even be reached in finite time provided the diffusion of cells is non-degenerate

  6. Boundedness in a chemotaxis-haptotaxis model with nonlinear diffusion

    Science.gov (United States)

    Li, Yan; Lankeit, Johannes

    2016-05-01

    This article deals with an initial-boundary value problem for the coupled chemotaxis-haptotaxis system with nonlinear diffusion under homogeneous Neumann boundary conditions in a bounded smooth domain Ω \\subset {{{R}}n} , n  =  2, 3, 4, where χ,ξ and μ are given nonnegative parameters. The diffusivity D(u) is assumed to satisfy D(u)≥slant δ {{u}m-1} for all u  >  0 with some δ >0 . It is proved that for sufficiently regular initial data global bounded solutions exist whenever m>2-\\frac{2}{n} . For the case of non-degenerate diffusion (i.e. D(0)  >  0) the solutions are classical; for the case of possibly degenerate diffusion (D(0)≥slant 0 ), the existence of bounded weak solutions is shown.

  7. Boundedness in a three-dimensional chemotaxis-haptotaxis model

    Science.gov (United States)

    Cao, Xinru

    2016-03-01

    This paper studies the chemotaxis-haptotaxis system left\\{begin{array}{lll} u_t = Δ u - χnabla \\cdot (unabla v) - ξnabla \\cdot (unabla w) + μ u(1 - u - w), &quad(x, t)in Ω × (0, T),\\ v_t = Δ v - v + u, &quad(x, t) in Ω × (0, T),\\ w_t= - vw, &quad(x, t)in Ω × (0,T) right.quadquad(star) under Neumann boundary conditions. Here, {Ω subset {{R}}^3} is a bounded domain with smooth boundary and the parameters {ξ,χ,μ > 0}. We prove that for nonnegative and suitably smooth initial data {(u_0, v_0, w_0)}, if {χ/μ} is sufficiently small, ({star}) possesses a global classical solution, which is bounded in {Ω × (0, infty)}. We underline that the result fully parallels the corresponding parabolic-elliptic-ODE system.

  8. Negative chemotaxis does not control quail neural crest cell dispersion.

    Science.gov (United States)

    Erickson, C A; Olivier, K R

    1983-04-01

    Negative chemotaxis has been proposed to direct dispersion of amphibian neural crest cells away from the neural tube (V. C. Twitty, 1949, Growth 13(Suppl. 9), 133-161). We have reexamined this hypothesis using quail neural crest and do not find evidence for it. When pigmented or freshly isolated neural crest cells are covered by glass shards to prevent diffusion of a "putative" chemotactic agent away from the cells and into the medium, we find a decrease in density of cells beneath the coverslip as did Twitty and Niu (1948, J. Exp. Zool. 108, 405-437). Unlike those investigators, however, we find the covered cells move slower than uncovered cells and that the decrease in density can be attributed to cessation of cell division and increased cell death in older cultures, rather than directed migration away from each other. In cell systems where negative chemotaxis has been demonstrated, a "no man's land" forms between two confronted explants (Oldfield, 1963, Exp. Cell Res. 30, 125-138). No such cell-free space forms between confronted neural crest explants, even if the explants are closely covered to prevent diffusion of the negative chemotactic material. If crest cell aggregates are drawn into capillary tubes to allow accumulation of the putative material, the cells disperse farther, the wider the capillary tube bore. This is contrary to what would be expected if dispersion depended on accumulation of this material. Also, no difference in dispersion is noted between cells in the center of the tubes versus cells near the mouth of the tubes where the tube medium is freely exchanging with external fresh medium. Alternative hypotheses for directionality of crest migration in vivo are discussed. PMID:6832483

  9. PsHint1, associated with the G-protein α subunit PsGPA1, is required for the chemotaxis and pathogenicity of Phytophthora sojae.

    Science.gov (United States)

    Zhang, Xin; Zhai, Chunhua; Hua, Chenlei; Qiu, Min; Hao, Yujuan; Nie, Pingping; Ye, Wenwu; Wang, Yuanchao

    2016-02-01

    Zoospore chemotaxis to soybean isoflavones is essential in the early stages of infection by the oomycete pathogen Phytophthora sojae. Previously, we have identified a G-protein α subunit encoded by PsGPA1 which regulates the chemotaxis and pathogenicity of P. sojae. In the present study, we used affinity purification to identify PsGPA1-interacting proteins, including PsHint1, a histidine triad (HIT) domain-containing protein orthologous to human HIT nucleotide-binding protein 1 (HINT1). PsHint1 interacted with both the guanosine triphosphate (GTP)- and guanosine diphosphate (GDP)-bound forms of PsGPA1. An analysis of the gene-silenced transformants revealed that PsHint1 was involved in the chemotropic response of zoospores to the isoflavone daidzein. During interaction with a susceptible soybean cultivar, PsHint1-silenced transformants displayed significantly reduced infectious hyphal extension and caused a strong cell death in plants. In addition, the transformants displayed defective cyst germination, forming abnormal germ tubes that were highly branched and exhibited apical swelling. These results suggest that PsHint1 not only regulates chemotaxis by interacting with PsGPA1, but also participates in a Gα-independent pathway involved in the pathogenicity of P. sojae. PMID:25976113

  10. Numerical study of plume patterns in the chemotaxis-diffusion-convection coupling system

    CERN Document Server

    Deleuze, Yannick; Thiriet, Marc; Sheu, Tony W H

    2015-01-01

    A chemotaxis-diffusion-convection coupling system for describing a form of buoyant convection in which the fluid develops convection cells and plume patterns will be investigated numerically in this study. Based on the two-dimensional convective chemotaxis-fluid model proposed in the literature, we developed an upwind finite element method to investigate the pattern formation and the hydrodynamical stability of the system. The numerical simulations illustrate different predicted physical regimes in the system. In the convective regime, the predicted plumes resemble B\\'enard instabilities. Our numerical results show how structured layers of bacteria are formed before bacterium rich plumes fall in the fluid. The plumes have a well defined spectrum of wavelengths and have an exponential growth rate, yet their position can only be predicted in very simple examples. In the chemotactic and diffusive regimes, the effects of chemotaxis are investigated. Our results indicate that the chemotaxis can stabilize the overa...

  11. Qualitative analysis of stationary Keller-Segel chemotaxis models with logistic growth

    Science.gov (United States)

    Wang, Qi; Yan, Jingda; Gai, Chunyi

    2016-06-01

    We study the stationary Keller-Segel chemotaxis models with logistic cellular growth over a one-dimensional region subject to the Neumann boundary condition. We show that nonconstant solutions emerge in the sense of Turing's instability as the chemotaxis rate {χ} surpasses a threshold number. By taking the chemotaxis rate as the bifurcation parameter, we carry out bifurcation analysis on the system to obtain the explicit formulas of bifurcation values and small amplitude nonconstant positive solutions. Moreover, we show that solutions stay strictly positive in the continuum of each branch. The stabilities of these steady-state solutions are well studied when the creation and degradation rate of the chemical is assumed to be a linear function. Finally, we investigate the asymptotic behaviors of the monotone steady states. We construct solutions with interesting patterns such as a boundary spike when the chemotaxis rate is large enough and/or the cell motility is small.

  12. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

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    Hidekazu Kuwayama

    Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

  13. Helicobacter pylori Requires TlpD-Driven Chemotaxis To Proliferate in the Antrum

    OpenAIRE

    Rolig, Annah S.; Shanks, James; Carter, J. Elliot; Ottemann, Karen M.

    2012-01-01

    Different disease outcomes of Helicobacter pylori infection correlate with distinct inflammation patterns. These different inflammatory distributions may be initiated by differences in bacterial localization. One H. pylori property known to affect murine stomach localization is chemotaxis, the ability to move in response to chemical cues. In this report, we used nonchemotactic mutants (Che−) to analyze whether chemotaxis is required for initial colonization of particular stomach regions or fo...

  14. Assessing the chemotaxis behavior of Physarum polycephalum to a range of simple volatile organic chemicals

    OpenAIRE

    de Lacy Costello, Ben P.J.; Adamatzky, Andrew I.

    2013-01-01

    The chemotaxis behavior of the plasmodial stage of the true slime mold Physarum Polycephalum was assessed when given a binary choice between two volatile organic chemicals (VOCs) placed in its environment. All possible binary combinations were tested between 19 separate VOCs selected due to their prevalence and biological activity in common plant and insect species. The slime mold exhibited positive chemotaxis toward a number of VOCs with the following order of preference:   Farnesene > β-myr...

  15. L-fucose influences chemotaxis and biofilm formation in Campylobacter jejuni.

    Science.gov (United States)

    Dwivedi, Ritika; Nothaft, Harald; Garber, Jolene; Xin Kin, Lin; Stahl, Martin; Flint, Annika; van Vliet, Arnoud H M; Stintzi, Alain; Szymanski, Christine M

    2016-08-01

    Campylobacter jejuni and Campylobacter coli are zoonotic pathogens once considered asaccharolytic, but are now known to encode pathways for glucose and fucose uptake/metabolism. For C. jejuni, strains with the fuc locus possess a competitive advantage in animal colonization models. We demonstrate that this locus is present in > 50% of genome-sequenced strains and is prevalent in livestock-associated isolates of both species. To better understand how these campylobacters sense nutrient availability, we examined biofilm formation and chemotaxis to fucose. C. jejuni NCTC11168 forms less biofilms in the presence of fucose, although its fucose permease mutant (fucP) shows no change. In a newly developed chemotaxis assay, both wild-type and the fucP mutant are chemotactic towards fucose. C. jejuni 81-176 naturally lacks the fuc locus and is unable to swim towards fucose. Transfer of the NCTC11168 locus into 81-176 activated fucose uptake and chemotaxis. Fucose chemotaxis also correlated with possession of the pathway for C. jejuni RM1221 (fuc+) and 81116 (fuc-). Systematic mutation of the NCTC11168 locus revealed that Cj0485 is necessary for fucose metabolism and chemotaxis. This study suggests that components for fucose chemotaxis are encoded within the fuc locus, but downstream signals only in fuc + strains, are involved in coordinating fucose availability with biofilm development. PMID:27145048

  16. Different migration patterns of sea urchin and mouse sperm revealed by a microfluidic chemotaxis device.

    Directory of Open Access Journals (Sweden)

    Haixin Chang

    Full Text Available Chemotaxis refers to a process whereby cells move up or down a chemical gradient. Sperm chemotaxis is known to be a strategy exploited by marine invertebrates such as sea urchins to reach eggs efficiently in moving water. Less is understood about how or whether chemotaxis is used by mammalian sperm to reach eggs, where fertilization takes place within the confinement of a reproductive tract. In this report, we quantitatively assessed sea urchin and mouse sperm chemotaxis using a recently developed microfluidic model and high-speed imaging. Results demonstrated that sea urchin Arbacia punctulata sperm were chemotactic toward the peptide resact with high chemotactic sensitivity, with an average velocity Vx up the chemical gradient as high as 20% of its average speed (238 μm/s, while mouse sperm displayed no statistically significant chemotactic behavior in progesterone gradients, which had been proposed to guide mammalian sperm toward eggs. This work demonstrates the validity of a microfluidic model for quantitative sperm chemotaxis studies, and reveals a biological insight that chemotaxis up a progesterone gradient may not be a universal strategy for mammalian sperm to reach eggs.

  17. Treatment with sulphated galactan inhibits macrophage chemotaxis and reduces intraplaque macrophage content in atherosclerotic mice.

    Science.gov (United States)

    Gomes Quinderé, Ana Luíza; Barros Benevides, Norma Maria; Pelli, Graziano; Lenglet, Sébastien; Burger, Fabienne; Carbone, Federico; Fraga-Silva, Rodrigo A; Stergiopulos, Nikolaos; Pagano, Sabrina; Bertolotto, Maria; Dallegri, Franco; Vuilleumier, Nicolas; Mach, François; Montecucco, Fabrizio

    2015-08-01

    Experimental data from animal models and clinical studies support connections between the haemostasis and inflammation in atherogenesis. These interfaces among inflammation and thrombogenesis have been suggested as targets for pharmacological intervention to reduce disease progression. We hypothesize that the recently discovered antithrombotic drug Sulphated Galactan (SG) (isolated from the red marine alga Acanthophora muscoides) might reduce atherosclerotic plaque vulnerability and inflammatory gene expression in 10-week aged apolipoprotein E deficient (ApoE-/-) mice under high-cholesterol diet for additional 11weeks. Then, the underlying cellular mechanisms were investigated in vitro. SG (10mg/kg) or Vehicle was subcutaneously injected from week 6 until week 11 of the diet. Treatment with SG reduced intraplaque macrophage and Tissue Factor (TF) content as compared to Vehicle-treated animals. Intraplaque TF co-localized and positively correlated with macrophage rich-areas. No changes on atherosclerotic plaque size, and other intraplaque features of vulnerability (such as lipid, neutrophil, MMP-9 and collagen contents) were observed. Moreover, mRNA expression of MMPs, chemokines and genetic markers of Th1/2/reg/17 lymphocyte polarization within mouse aortic arches and spleens was not affected by SG treatment. In vitro, treatment with SG dose-dependently reduced macrophage chemotaxis without affecting TF production. Overall, the chronic SG treatment was well tolerated. In conclusion, our results indicate that SG treatment reduced intraplaque macrophage content (by impacting on cell recruitment) and, concomitantly, intraplaque TF content of potential macrophage origin in atherosclerotic mice. PMID:25869506

  18. Construction and Expression of Eukaryotic Expressing Vector pCH510 of Polypeptide CH50 and Its Chemotaxis and Antitumor Function by in vivo Transfection

    Institute of Scientific and Technical Information of China (English)

    李东; 冯作化; 叶仕桥; 张桂梅; 张慧; 黄波; 肖徽

    2001-01-01

    To construct an eukaryotic expressing vector that expresses CH50, a recombinant CellⅠ-HepⅡ bifunctional-domain polypeptide of human fibronectin, and to investigate the chemotaxis to immune cells and the inhibitory effect on the growth of tumor by the expression of the plasmid in vivo, the plasmid was constructed by DNA recombination. Gene transfection was performed in vitro and in vivo. The expressed product was identified by Western blot. The chemotaxis after gene transfection in vivo was observed by histotomy and staining of muscle tissues. The inhibition of gene transfection on solid tumor was observed in mice. The results showed that plasmid pCH510 was constructed by the recombination of the 5′-terminal noncoding region and signal peptide coding region of human fibronectin cDNA and cDNA fragment coding CH50 polypeptide with a 3′-terminal noncoding region of human FN cDNA, and the insertion of the recombinated fragment into plasmid pcDNA3.1. After transfection with plasmid pCH510, NIH3T3 cells could produce CH50 polypeptide. The transfection of plasmid pCH510 by the injection in muscle of mouse could produce the effects of chemotaxis on immune cells and the inhibition on the growth of solid tumor. It is concluded that plasmid pCH510 can express in cells and in vivo in mouse. The expression of the plasmid in vivo has a chemotactic effect on immune cells and can inhibit the growth of solid tumor.

  19. A PEG-DA microfluidic device for chemotaxis studies

    International Nuclear Information System (INIS)

    The study of cells in a well-defined and chemically programmable microenvironment is essential for a complete and fundamental understanding of the cell behaviors with respect to specific chemical compounds. Flow-free microfluidic devices that generate quasi-steady chemical gradients (spatially varying but temporally constant) have been demonstrated as effective chemotaxis assay platforms due to dissociating the effect of chemical cues from mechanical shear forces caused by fluid flow. In this work, we demonstrate the fabrication and characterization of a flow-free microfluidic platform made of polyethylene glycol diacrylate (PEG-DA) hydrogel. We have demonstrated that the mass transport properties of these devices can be customized by fabricating them from PEG-DA gels of four distinct molecular weights. In contrast to microfluidic devices developed using soft lithography; this class of devices can be realized using a more cost-effective approach of direct photopolymerization with fewer microfabrication steps. This microfluidic platform was tested by conducting a quantitative study of the chemotactic behavior of Escherichia coli (E. coli) RP437, a model microorganism, in presence of the chemo-effector, casamino-acids. Using the microfabrication and characterization methodology presented in this work, microfluidic platforms with well-defined and customizable diffusive properties can be developed to accommodate the study of a wide range of cell types. (paper)

  20. Effective Medium Equations for Chemotaxis in Porous Media

    Science.gov (United States)

    Valdes-Parada, F.; Porter, M.; Wood, B. D.; Narayanaswamy, K.; Ford, R.

    2008-12-01

    Biodegradation is an important mechanism for contaminant reduction in groundwater environments; in fact, in-situ bioremediation and bioaugmentation methods represent alternatives to traditional methods such as pump-and-treat. Chemotaxis has been shown to enhance bacterial transport toward or away from concentration gradients of chemical species in laboratory experiments and may signifficantly increase contaminant flux undergoing degradation at the interfaces of low- and high-permeability regions. In this work, the method of volume averaging is used to upscale the microscale description of chemotactic microbial transport in order to obtain the corresponding macroscale equations for bacteria and the chemoattractant. As a first apprach, cellular growth/death and consumption of the attractant by chemical reaction are assumed negligible with respect to convective and diffusive transport, in both levels of scale. For bacteria, two effective coefficients are introduced, namely a total motility tensor and an effective chemotactic sensitivity tensor. Both coefficients are computed by solving the associated closure problems in a capillary tube. Analysis of breakthrough curves resulting from numerical experiments is also presented.

  1. Colony specificity and chemotaxis in the compound ascidian Botryllus schlosseri.

    Science.gov (United States)

    Cima, Francesca; Sabbadin, Armando; Zaniolo, Giovanna; Ballarin, Loriano

    2006-11-01

    We re-investigated the behavior of hemocytes during the non-fusion (rejection) reaction between genetically incompatible colonies of the ascidian Botryllus schlosseri. In the course of the reaction, hemocytes - mainly morula cells - crowd inside the blind ends of marginal vascular vessels (known as ampullae) of the colonial leading edge (LE) facing the foreign colony which suggests the occurrence of chemotactic attraction of circulating hemocytes towards the ampullar lumen. Then, cells migrate, through the ampullar tips, into the partially fused tunics and contribute to the formation of the necrotic spots along the contact borders which characterize the reaction. Studies on histological sections clearly indicate that, although morula cell concentration is always higher in ampullae of the LE than in those of the lateral (L) part of the colony, their frequency significantly increases in LE ampullae of rejecting colonies with respect to LE ampullae of both fusing and isolated colonies. In addition, in vitro chemotaxis experiments demonstrated that blood plasma from incompatible colonies can stimulate morula cell migration through polycarbonate filters and this passage is inhibited by antibodies raised against mammalian pro-inflammatory cytokines. The possible nature and role of molecules recognized by anti-cytokine antibodies in hemocyte migration are discussed. PMID:16962802

  2. Novel methyl transfer during chemotaxis in Bacillus subtilis

    International Nuclear Information System (INIS)

    If Bacillus subtilis is incubated in radioactive methionine in the absence of protein synthesis, the methyl-accepting chemotaxis proteins (MCPs) become radioactively methylated. If the bacteria are further incubated in excess nonradioactive methionine (cold-chased) and then given the attractant aspartate, the MCPs lose about half of their radioactivity due to turnover, in which lower specific activity methyl groups from S-adenosylmethionine (AdoMet) replace higher specific activity ones. Due to the cold-chase, the specific activity of the AdoMet pool is reduced at least 2-fold. If, later, the attractant is removed, higher specific activity methyl groups return to the MCPs. Thus, there must exist an unidentified methyl carrier than can reversibly receive methyl groups from the MCPs. In a similar experiment, labeled cells were transferred to a flow cell and exposed to addition and removal of attractant and of repellent. All four kinds of stimuli were found to cause methanol production. Bacterial with maximally labeled MCPs were exposed to many cycles of addition and removal of attractant; the maximum amount of radioactive methanol was evolved on the third, not the first, cycle. This result suggests that there is a precursor-product relationship between methyl groups on the MCPs and on the unidentified carrier, which might be the direct source of methanol. However, since no methanol was produced when a methyltransferase mutant, whose MCPs were unmethylated, was exposed to addition and removal of attractant or repellent, the methanol must ultimately derive from methylated MCPs

  3. Theory of optimal information transmission in E. coli chemotaxis pathway

    Science.gov (United States)

    Micali, Gabriele; Endres, Robert G.

    Bacteria live in complex microenvironments where they need to make critical decisions fast and reliably. These decisions are inherently affected by noise at all levels of the signaling pathway, and cells are often modeled as an input-output device that transmits extracellular stimuli (input) to internal proteins (channel), which determine the final behavior (output). Increasing the amount of transmitted information between input and output allows cells to better infer extracellular stimuli and respond accordingly. However, in contrast to electronic devices, the separation into input, channel, and output is not always clear in biological systems. Output might feed back into the input, and the channel, made by proteins, normally interacts with the input. Furthermore, a biological channel is affected by mutations and can change under evolutionary pressure. Here, we present a novel approach to maximize information transmission: given cell-external and internal noise, we analytically identify both input distributions and input-output relations that optimally transmit information. Using E. coli chemotaxis as an example, we conclude that its pathway is compatible with an optimal information transmission device despite the ultrasensitive rotary motors.

  4. Effects of receptor modification and temperature on dynamics of sensory complexes in Escherichia coli chemotaxis

    Directory of Open Access Journals (Sweden)

    Grosse Karin

    2011-10-01

    Full Text Available Abstract Background Extracellular stimuli in chemotaxis of Escherichia coli and other bacteria are processed by large clusters of sensory complexes. The stable core of these clusters is formed by transmembrane receptors, a kinase CheA, and an adaptor CheW, whereas adaptation enzymes CheR and CheB dynamically associate with the clusters via interactions with receptors and/or CheA. Several biochemical studies have indicated the dependence of the sensory complex stability on the adaptive modification state of receptors and/or on temperature, which may potentially allow environment-dependent tuning of its signalling properties. However, the extent of such regulation in vivo and its significance for chemotaxis remained unclear. Results Here we used fluorescence recovery after photobleaching (FRAP to confirm in vivo that the exchange of CheA and CheW shows a modest dependency on the level of receptor modification/activity. An even more dramatic effect was observed for the exchange kinetics of CheR and CheB, indicating that their association with clusters may depend on the ability to bind substrate sites on receptors and on the regulatory phosphorylation of CheB. In contrast, environmental temperature did not have a discernible effect on stability of the cluster core. Strain-specific loss of E. coli chemotaxis at high temperature could instead be explained by a heat-induced reduction in the chemotaxis protein levels. Nevertheless, high basal levels of chemotaxis and flagellar proteins in common wild type strains MG1655 and W3110 enabled these strains to maintain their chemotactic ability up to 42°C. Conclusions Our results confirmed that clusters formed by less modified receptors are more dynamic, which can explain the previously observed adjustment of the chemotaxis response sensitivity according to the level of background stimulation. We further propose that the dependency of CheR exchange on the availability of unmethylated sites on receptors is

  5. Neutrophil adhesion and chemotaxis depend on substrate mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

    2010-05-19

    Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

  6. N-Formylmethionyl Peptide Receptors on Equine Leukocytes Initiate Secretion but not Chemotaxis

    Science.gov (United States)

    Snyderman, Ralph; Pike, Marilyn C.

    1980-07-01

    The chemotaxis of leukocytes appears to be initiated by the binding of chemotactic factors to the surface of these cells. N-Formylated peptides induce chemotaxis and lysosomal enzyme secretion of leukocytes; because these peptides are available in a purified radiolabeled form, they have been useful in the characterization of receptors for chemotactic factors. Equine polymorphonuclear leukocytes secrete lysosomal enzymes but do not exhibit chemotaxis in response to the N-formylated peptides, even though they have a high-affinity cell surface receptor for these agents. The specificity of the equine receptor resembles the specificity of the receptor on chemotactically responsive leukocytes from other species. Equine polymorphonuclear leukocytes may thus be an excellent model for the study of the events that lead to a biological response following receptor occupancy.

  7. Role of motility and chemotaxis in the pathogenesis of Dickeya dadantii 3937 (ex Erwinia chrysanthemi 3937).

    Science.gov (United States)

    Antúnez-Lamas, María; Cabrera-Ordóñez, Ezequiel; López-Solanilla, Emilia; Raposo, Rosa; Trelles-Salazar, Oswaldo; Rodríguez-Moreno, Andrés; Rodríguez-Palenzuela, Pablo

    2009-02-01

    Dickeya dadantii 3937 (ex Erwinia chrysanthemi), a member of the Enterobacteriaceae, causes soft rot in many economically important crops. A successful pathogen has to reach the interior of the plant in order to cause disease. To study the role of motility and chemotaxis in the pathogenicity of D. dadantii 3937, genes involved in the chemotactic signal transduction system (cheW, cheB, cheY and cheZ) and in the structure of the flagellar motor (motA) were mutagenized. All the mutant strains grew like the wild-type in culture media, and the production and secretion of pectolytic enzymes was not affected. As expected, the swimming ability of the mutant strains was reduced with respect to the wild-type: motA (94%), cheY (80%), cheW (74%), cheB (54%) and cheZ (48%). The virulence of the mutant strains was analysed in chicory, Saintpaulia and potato. The mutant strains were also tested for their capability to enter into Arabidopsis leaves. All the mutants showed a significant decrease of virulence in certain hosts; however, the degree of virulence reduction varied depending on the virulence assay. The ability to penetrate Arabidopsis leaves was impaired in all the mutants, whereas the capacity to colonize potato tubers after artificial inoculation was affected in only two mutant strains. In general, the virulence of the mutants could be ranked as motA

  8. Asymptotic dynamics on a singular chemotaxis system modeling onset of tumor angiogenesis

    Science.gov (United States)

    Wang, Zhi-An; Xiang, Zhaoyin; Yu, Pei

    2016-02-01

    The asymptotic behavior of solutions to a singular chemotaxis system modeling the onset of tumor angiogenesis in two and three dimensional whole spaces is investigated in the paper. By a Cole-Hopf type transformation, the singular chemotaxis is converted into a non-singular hyperbolic system. Then we study the transformed system and establish the global existence, asymptotic decay rates and diffusion convergence rate of solutions by the method of energy estimates. The main novelty of our results is the finding of a hidden interactive dissipation structure in the system by which the energy dissipation is established.

  9. Generalized Keller-Segel models of chemotaxis. Analogy with nonlinear mean field Fokker-Planck equations

    CERN Document Server

    Chavanis, Pierre-Henri

    2008-01-01

    We consider a generalized class of Keller-Segel models describing the chemotaxis of biological populations (bacteria, amoebae, endothelial cells, social insects,...). We show the analogy with nonlinear mean field Fokker-Planck equations and generalized thermodynamics. As an illustration, we introduce a new model of chemotaxis incorporating both effects of anomalous diffusion and exclusion principle (volume filling). We also discuss the analogy between biological populations described by the Keller-Segel model and self-gravitating Brownian particles described by the Smoluchowski-Poisson system.

  10. Genetic control of immune response in carriers of ancestral haplotype 8.1: the study of chemotaxis.

    Science.gov (United States)

    Candore, Giuseppina; Balistreri, Carmela R; Campagna, Anna Maria; Colombo, Alfredo; Cuppari, Irene; Di-Carlo, Daniele; Grimaldi, Maria P; Orlando, Valentina; Piazza, Giuseppina; Vasto, Sonya; Lio, Domenico; Caruso, Calogero

    2006-11-01

    In all caucasian populations the association of an impressive number of autoimmune diseases with genes from the HLA-B8, DR3 haplotype that is part of the ancestral haplotype (AH) 8.1 HLA-A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201 has been reported by different research groups. This haplotype, which is more common in northern Europe, is also associated with a number of immune system dysfunctions in healthy subjects. Analyzing the data according to gender, some dysfunctions are observed in women but not in men, in agreement with the role of X-linked genes and/or estrogens in the development and progression of autoimmune diseases. It has been proposed that a small number of genes within the 8.1 AH modify immune responsiveness and hence affect multiple immunopathological diseases. In this article, we demonstrate that neutrophil chemotaxis is significantly decreased in carriers of this AH, suggesting that this impairment may also be related to the increased occurrence of autoimmune diseases in these individuals. PMID:17261794

  11. Lauric acid in crown daisy root exudate potently regulates root-knot nematode chemotaxis and disrupts Mi-flp-18 expression to block infection.

    Science.gov (United States)

    Dong, Linlin; Li, Xiaolin; Huang, Li; Gao, Ying; Zhong, Lina; Zheng, Yuanyuan; Zuo, Yuanmei

    2014-01-01

    Tomato (Solanum lycopersicum) crops can be severely damaged due to parasitism by the root-knot nematode (RKN) Meloidogyne incognita, but are protected when intercropped with crown daisy (Chrysanthemum coronarium L.). Root exudate may be the determining factor for this protection. An experiment using pots linked by a tube and Petri dish experiments were undertaken to confirm that tomato-crown daisy intercropping root exudate decreased the number of nematodes and alleviated nematode damage, and to determine crown daisy root exudate-regulated nematode chemotaxis. Following a gas chromatography-mass spectrometry assay, it was found that the intercropping protection was derived from the potent bioactivity of a specific root exudate component of crown daisy, namely lauric acid. The Mi-flp-18 gene, encoding an FMRFamide-like peptide neuromodulator, regulated nematode chemotaxis and infection by RNA interference. Moreover, it was shown that lauric acid acts as both a lethal trap and a repellent for M. incognita by specifically regulating Mi-flp-18 expression in a concentration-dependent manner. Low concentrations of lauric acid (0.5-2.0mM) attract M. incognita and consequently cause death, while high concentrations (4.0mM) repel M. incognita. This study elucidates how lauric acid in crown daisy root exudate regulates nematode chemotaxis and disrupts Mi-flp-18 expression to alleviate nematode damage, and presents a general methodology for studying signalling systems affected by plant root exudates in the rhizosphere. This could lead to the development of economical and feasible strategies for controlling plant-parasitic nematodes, and provide an alternative to the use of pesticides in farming systems. PMID:24170741

  12. Quantitative investigation of bacterial chemotaxis at the single-cell level

    Science.gov (United States)

    Min, Taejin

    Living cells sense and respond to constantly changing environmental conditions. Depending on the type of stimuli, the cell may response by altering gene expression pattern, secreting molecules, or migrating to a different environment. Directed movement of cells in response to chemical stimuli is called chemotaxis. In bacterial chemotaxis, small extracellular molecules bind receptor proteins embedded in the cell membrane, which then transmit the signal inside the cell through a cascade of protein-protein interactions. This chain of events influences the behavior of motor proteins that drive the rotation of helical filaments called flagella. Individual cells of the gut-dwelling bacteria Escherichia coli (E. coli) have many such flagella, whose collective action results in the swimming behavior of the cell. A recent study found that in absence of chemical stimuli, fluctuations in the protein cascade can cause non-Poissonian switching behavior in the flagellar motor (2). A corollary was that extension of such behavior to the whole-cell swimming level would have implications for E. coli's foraging strategy. However, existence of such behavior at the swimming cell level could not be predicted a priori, since the mapping from single flagellum behavior to the swimming behavior of a multi-flagellated cell is complex and poorly understood (3, 4). Here we characterize the chemotactic behavior of swimming E. coli cells using a novel optical trap-based measurement technique. This technique allows us to trap individual cells and monitor their swimming behavior over long time periods with high temporal resolution. We find that swimming cells exhibit non-Poissonian switching statistics between different swimming states, in a manner similar to the rotational direction-switching behavior seen in individual flagella. Furthermore, we develop a data analysis routine that allows us to characterize higher order swimming features such as reversal of swimming direction and existence of

  13. On convergence to equilibria for the Keller-Segel chemotaxis model

    Czech Academy of Sciences Publication Activity Database

    Feireisl, Eduard; Laurencot, P.; Petzeltová, Hana

    2007-01-01

    Roč. 236, č. 2 (2007), s. 551-569. ISSN 0022-0396 R&D Projects: GA AV ČR(CZ) IAA100190606 Institutional research plan: CEZ:AV0Z10190503 Keywords : Keller-Segel chemotaxis model * convergence to equilibria * Łojasiewicz-Simon theory Subject RIV: BA - General Mathematics Impact factor: 1.097, year: 2007

  14. Effects of Ventriculoperitoneal Shunt on the Neutrophil Chemotaxis and NBT in Hydrocephalic Children

    Directory of Open Access Journals (Sweden)

    F Nejat

    2005-11-01

    Full Text Available Background: Hydrocephalus is a hydrodynamic disturbance of cerebrospinal fluid (CSF that increases the intracranial volume of CSF. Ventriculo-peritoneal shunt, that diverts CSF from the ventricle, is the most common treatment for hydrocephalus. Infection is the most common complication of ventriculo-peritoneal shunt. The role of immune system in shunt infection has been studied before. We did this study to evaluate the effect of shunt catheter on nitro blue tetrazolium (NBT assay and neutrophil chemotaxis. Methods: In this experimental, a before after study was conducted on 24 hydrocephalic children who had underwent ventriculo-peritoneal shunt operation in Children’s Medical Center. Neutrophil count, chemotaxis and NBT were studied before operation and 2 months thereafter. Findings: There was no statistically significant difference in neutrophil count, chemotaxis and NBT in patients before and after shunt operation. The age of patients at the time of surgery, etiology and duration of hydrocephalus, before operation and shunt infection did not have any significant effect on these tests. Conclusion: Ventriculo-peritoneal shunt catheter could not induce systemic effect on neutrophil count, chemotaxis and NBT.

  15. Chemotaxis in the cellular slime molds : I. The effect of temperature

    NARCIS (Netherlands)

    Konijn, Theo M.

    1965-01-01

    The effect of temperature on chemotaxis in the cellular slime mold Dictyostelium discoideum has been studied by incubating small populations of washed myxamoebae at different temperatures. Droplets containing a cell suspension of known density were deposited on a hydrophobic agar surface. The myxamo

  16. The Pseudomonas aeruginosa chemotaxis methyltransferase CheR1 impacts on bacterial surface sampling.

    Directory of Open Access Journals (Sweden)

    Juliane Schmidt

    Full Text Available The characterization of factors contributing to the formation and development of surface-associated bacterial communities known as biofilms has become an area of intense interest since biofilms have a major impact on human health, the environment and industry. Various studies have demonstrated that motility, including swimming, swarming and twitching, seems to play an important role in the surface colonization and establishment of structured biofilms. Thereby, the impact of chemotaxis on biofilm formation has been less intensively studied. Pseudomonas aeruginosa has a very complex chemosensory system with two Che systems implicated in flagella-mediated motility. In this study, we demonstrate that the chemotaxis protein CheR1 is a methyltransferase that binds S-adenosylmethionine and transfers a methyl group from this methyl donor to the chemoreceptor PctA, an activity which can be stimulated by the attractant serine but not by glutamine. We furthermore demonstrate that CheR1 does not only play a role in flagella-mediated chemotaxis but that its activity is essential for the formation and maintenance of bacterial biofilm structures. We propose a model in which motility and chemotaxis impact on initial attachment processes, dispersion and reattachment and increase the efficiency and frequency of surface sampling in P. aeruginosa.

  17. Fluid flow and particle dynamics inside an evaporating droplet containing live bacteria displaying chemotaxis.

    Science.gov (United States)

    Thokchom, Ashish Kumar; Swaminathan, Rajaram; Singh, Anugrah

    2014-10-21

    Evaporation-induced particle deposition patterns like coffee rings provide easy visual identification that is beneficial for developing inexpensive and simple diagnostic devices for detecting pathogens. In this study, the effect of chemotaxis on such pattern formation has been realized experimentally in drying droplets of bacterial suspensions. We have investigated the velocity field, concentration profile, and deposition pattern in the evaporating droplet of Escherichia coli suspension in the presence and absence of nutrients. Flow visualization experiments using particle image velocimetry (PIV) were carried out with E. coli bacteria as biological tracer particles. Experiments were conducted for suspensions of motile (live) as well as nonmotile (dead) bacteria. In the absence of any nutrient gradient like sugar on the substrate, both types of bacterial suspension showed two symmetric convection cells and a ring like deposition of particles after complete evaporation. Interestingly, the droplet containing live bacterial suspension showed a different velocity field when the sugar was placed at the base of the droplet. This can be attributed to the chemoattractant nature of the sugar, which induced chemotaxis among live bacteria targeted toward the nutrient site. Deposition of the suspended bacteria was also displaced toward the nutrient site as the evaporation proceeded. Our experiments demonstrate that both velocity fields and concentration patterns can be altered by chemotaxis to modify the pattern formation in evaporating droplet containing live bacteria. These results highlight the role of bacterial chemotaxis in modifying coffee ring patterns. PMID:25229613

  18. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A

    2010-12-01

    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  19. Transient dynamic phenotypes as criteria for model discrimination: fold-change detection in Rhodobacter sphaeroides chemotaxis.

    Science.gov (United States)

    Hamadeh, Abdullah; Ingalls, Brian; Sontag, Eduardo

    2013-03-01

    The chemotaxis pathway of the bacterium Rhodobacter sphaeroides shares many similarities with that of Escherichia coli. It exhibits robust adaptation and has several homologues of the latter's chemotaxis proteins. Recent theoretical results have correctly predicted that the E. coli output behaviour is unchanged under scaling of its ligand input signal; this property is known as fold-change detection (FCD). In the light of recent experimental results suggesting that R. sphaeroides may also show FCD, we present theoretical assumptions on the R. sphaeroides chemosensory dynamics that can be shown to yield FCD behaviour. Furthermore, it is shown that these assumptions make FCD a property of this system that is robust to structural and parametric variations in the chemotaxis pathway, in agreement with experimental results. We construct and examine models of the full chemotaxis pathway that satisfy these assumptions and reproduce experimental time-series data from earlier studies. We then propose experiments in which models satisfying our theoretical assumptions predict robust FCD behaviour where earlier models do not. In this way, we illustrate how transient dynamic phenotypes such as FCD can be used for the purposes of discriminating between models that reproduce the same experimental time-series data. PMID:23293140

  20. Chemotaxis Increases the Residence Time of Bacteria in Granular Media Containing Distributed Contaminant Sources.

    Science.gov (United States)

    Adadevoh, Joanna S T; Triolo, Sarah; Ramsburg, C Andrew; Ford, Roseanne M

    2016-01-01

    The use of chemotactic bacteria in bioremediation has the potential to increase access to, and the biotransformation of, contaminant mass within the subsurface. This laboratory-scale study aimed to understand and quantify the influence of chemotaxis on the residence times of pollutant-degrading bacteria within homogeneous treatment zones. Focus was placed on a continuous-flow sand-packed column in which a uniform distribution of naphthalene crystals created distributed sources of dissolved-phase contaminant. A 10 mL pulse of Pseudomonas putida G7, which is chemotactic to naphthalene, and Pseudomonas putida G7 Y1, a nonchemotactic mutant strain, were simultaneously introduced into the sand-packed column at equal concentrations. Breakthrough curves obtained from experiments conducted with and without naphthalene were used to quantify the effect of chemotaxis on transport parameters. In the presence of the chemoattractant, longitudinal dispersion of PpG7 increased by a factor of 3, and percent recovery decreased by 43%. In contrast, PpG7 Y1 transport was not influenced by the presence of naphthalene. The results imply that pore-scale chemotaxis responses are evident at an interstitial velocity of 1.8 m/day, which is within the range of typical groundwater flow. Within the context of bioremediation, chemotaxis may work to enhance bacterial residence times in zones of contamination, thereby improving treatment. PMID:26605857

  1. A strain isolated from gas oil-contaminated soil displays chemotaxis towards gas oil and hexadecane.

    Science.gov (United States)

    Lanfranconi, Mariana P; Alvarez, Héctor M; Studdert, Claudia A

    2003-10-01

    In this report we describe the isolation of a strain from soil contaminated with gas oil by taking bacteria from a chemotactic ring on gas oil-containing soft agar plates. Partial 16 S rDNA sequencing of the isolated strain showed 99.1% identity with Flavimonas oryzihabitans. It was not only able to degrade different aliphatic hydrocarbons but it was also chemotactic towards gas oil and hexadecane, as demonstrated by the use of three different chemotaxis methods, such as agarose plug and capillary assays and swarm plate analysis. In addition, the strain was chemotactic to a variety of carbon sources that serve as growth substrates, including glucose, arabinose, mannitol, glycerol, gluconate, acetate, succinate, citrate, malate, lactate and casaminoacids. This is the first report on chemotaxis of a hydrocarbon-degrading bacterium towards a pure alkane, such as hexadecane. The fact that environmental isolates show chemotaxis towards contaminant/s present in the site of isolation suggests that chemotaxis might enhance biodegradation by favouring contact between the degrading microorganism and its substrate. PMID:14510854

  2. Chemotaxis to furan compounds by furan-degrading Pseudomonas strains

    Science.gov (United States)

    Two Pseudomonas strains known to utilize furan derivatives were shown to be attracted to furfural, 5-hydroxymethylfurfural, furfuryl alcohol, and 2-furoic acid in the absence of furan metabolism. In addition, a LysR-family regulatory protein known to regulate furan metabolic genes was found to be i...

  3. Ammonia differentially suppresses the cAMP chemotaxis of anterior-like cells and prestalk cells in Dictyostelium discoideum

    Indian Academy of Sciences (India)

    Ira N Feit; Erika J Medynski; Michael J Rothrock

    2001-06-01

    A drop assay for chemotaxis to cAMP confirms that both anterior-like cells (ALC) and prestalk cells (pst cells) respond to cAMP gradients. We present evidence that the chemotactic response of both ALC and pst cells is suppressed by ammonia, but a higher concentration of ammonia is required to suppress the response in pst cells. ALC show a chemotactic response to cAMP when moving on a substratum of prespore cells in isolated slug posteriors incubated under oxygen. ALC chemotaxis on a prespore cell substratum is suppressed by the same concentration of ammonia that suppresses ALC chemotaxis on the agar substratum in drop assays. Chemotaxis suppression is mediated by the unprotonated (NH3) species of ammonia. The observed suppression, by ammonia, of ALC chemotaxis to cAMP supports our earlier hypothesis that ammonia is the tip-produced suppressor of such chemotaxis. We discuss implications of ammonia sensitivity of pst cells and ALC with regard to the movement and localization of ALC and pst cells in the slug and to the roles played by ALC in fruiting body formation. In addition, we suggest that a progressive decrease in sensitivity to ammonia is an important part of the maturation of ALC into pst cells.

  4. Role of chemotaxis in the transport of bacteria through saturated porous media

    Science.gov (United States)

    Ford, R.M.; Harvey, R.W.

    2007-01-01

    Populations of chemotactic bacteria are able to sense and respond to chemical gradients in their surroundings and direct their migration toward increasing concentrations of chemicals that they perceive to be beneficial to their survival. It has been suggested that this phenomenon may facilitate bioremediation processes by bringing bacteria into closer proximity to the chemical contaminants that they degrade. To determine the significance of chemotaxis in these processes it is necessary to quantify the magnitude of the response and compare it to other groundwater processes that affect the fate and transport of bacteria. We present a systematic approach toward quantifying the chemotactic response of bacteria in laboratory scale experiments by starting with simple, well-defined systems and gradually increasing their complexity. Swimming properties of individual cells were assessed from trajectories recorded by a tracking microscope. These properties were used to calculate motility and chemotaxis coefficients of bacterial populations in bulk aqueous media which were compared to experimental results of diffusion studies. Then effective values of motility and chemotaxis coefficients in single pores, pore networks and packed columns were analyzed. These were used to estimate the magnitude of the chemotactic response in porous media and to compare with dispersion coefficients reported in the field. This represents a compilation of many studies over a number of years. While there are certainly limitations with this approach for ultimately quantifying motility and chemotaxis in granular aquifer media, it does provide insight into what order of magnitude responses are possible and which characteristics of the bacteria and media are expected to be important. ?? 2006 Elsevier Ltd. All rights reserved.

  5. Assessing the chemotaxis behavior of Physarum polycephalum to a range of simple volatile organic chemicals.

    Science.gov (United States)

    de Lacy Costello, Ben P J; Adamatzky, Andrew I

    2013-09-01

    The chemotaxis behavior of the plasmodial stage of the true slime mold Physarum Polycephalum was assessed when given a binary choice between two volatile organic chemicals (VOCs) placed in its environment. All possible binary combinations were tested between 19 separate VOCs selected due to their prevalence and biological activity in common plant and insect species. The slime mold exhibited positive chemotaxis toward a number of VOCs with the following order of preference:   Farnesene > β-myrcene > tridecane > limonene > p-cymene > 3-octanone > β-pinene > m-cresol > benzylacetate > cis-3-hexenylacetate. For the remaining compounds, no positive chemotaxis was observed in any of the experiments, and for most compounds there was an inhibitory effect on the growth of the slime mold. By assessing this lack of growth or failure to propagate, it was possible to produce a list of compounds ranked in terms of their inhibitory effect: nonanal > benzaldehyde > methylbenzoate > linalool > methyl-p-benzoquinone > eugenol > benzyl alcohol > geraniol > 2-phenylethanol. This analysis shows a distinct preference of the slime mold for non-oxygenated terpene and terpene-like compounds (farnesene, β-myrcene, limonene, p-cymene and β-pinene). In contrast, terpene-based alcohols such as geraniol and linalool were found to have a strong inhibitory effect on the slime mold. Both the aldehydes utilized in this study had the strongest inhibitory effect on the slime mold of all the 19 VOCs tested. Interestingly, 3-octanone, which has a strong association with a "fungal odor," was the only compound with an oxygenated functionality where Physarum Polycephalum exhibits distinct positive chemotaxis. PMID:24265848

  6. Weighted weak formulation for a nonlinear degenerate parabolic equation arising in chemotaxis or porous media

    OpenAIRE

    Ibrahim, Moustafa; Saad, Mazen

    2015-01-01

    This paper is devoted to the mathematical analysis of a degenerate nonlinear parabolic equation. This kind of equations stems either from the modeling of a compressible two phase flow in porous media or from the modeling of a chemotaxis-fluid process. In the degenerate equation, the strong nonlinearities are technically difficult to be controlled by the degenerate dissipative term because the equation itself presents degenerate terms of order 0 and of order 1. In the case of the sub-quadratic...

  7. A System of Non-linear Partial Differential Equations Modeling Chemotaxis with Sensitivity Functions

    OpenAIRE

    Post, Katharina

    1999-01-01

    Wir betrachten ein System nichtlinearer parabolischer partieller Differentialgleichungen zur Modellierung des biologischen Phänomens Chemotaxis, das unter anderem in Aggregationsprozessen in Lebenszyklen bestimmter Einzeller eine wichtige Rolle spielt. Unser Chemotaxismodell benutzt Sensitivitäts funktionen, die die vorkommenden biologischen Prozesse genauer spezifizieren. Trotz der durch die Sensitivitätsfunktionen eingebrachten, zusätzlichen Nichtlinearitäten in den Gleichungen erhalten w...

  8. Chemotaxis to aromatic and hydroaromatic acids: comparison of Bradyrhizobium japonicum and Rhizobium trifolii.

    OpenAIRE

    Parke, D; Rivelli, M; Ornston, L N

    1985-01-01

    Rhizobia are bacteria well known for their ability to fix nitrogen in symbiosis with leguminous plants. Members of diverse rhizobial species grow at the expense of hydroaromatic and aromatic compounds commonly found in plant cells and plant litter. Using a quantitative capillary assay to measure chemotaxis, we tested the ability of hydroaromatic acids, selected aromatic acids, and their metabolites to serve as chemoattractants for two distantly related rhizobial species, Bradyrhizobium japoni...

  9. Effects of antimicrobial agents on growth and chemotaxis of Trichomonas vaginalis.

    OpenAIRE

    Sugarman, B; Mummaw, N

    1988-01-01

    The motility of viable Trichomonas vaginalis organisms is readily demonstrable in a clinical wet mount or cultured specimens. We attempted to determine whether migration is a dynamic process such that the organisms move to avoid exposure to toxic antimicrobial agents. With the use of axenic cultures of T. vaginalis that were radiolabeled and assayed for chemotaxis in plastic multiwelled plates with a membrane filter inserted to trap organisms, the response of clinical isolates to various anti...

  10. Two different mechanisms mediate chemotaxis to inorganic phosphate in Pseudomonas aeruginosa

    Science.gov (United States)

    Rico-Jiménez, Miriam; Reyes-Darias, Jose Antonio; Ortega, Álvaro; Díez Peña, Ana Isabel; Morel, Bertrand; Krell, Tino

    2016-01-01

    Inorganic phosphate (Pi) is a central signaling molecule that modulates virulence in various pathogens. In Pseudomonas aeruginosa, low Pi concentrations induce transcriptional alterations that increase virulence. Also, under low Pi levels, P. aeruginosa exhibits Pi chemotaxis—a process mediated by the two non-paralogous receptors CtpH and CtpL. Here we show that the two receptors operate via different mechanisms. We demonstrate that the ligand binding domain (LBD) of CtpH but not CtpL binds Pi directly. We identify the periplasmic ligand binding protein PstS as the protein that binds in its Pi loaded state to CtpL, resulting in receptor stimulation. PstS forms part of the Pi transporter and has thus a double function in Pi transport and chemotaxis. The affinity of Pi for CtpH was modest whereas that for PstS very high, which may explain why CtpH and CtpL mediate chemotaxis to high and low Pi concentrations, respectively. The pstS/ctpH double mutant was almost devoid of Pi taxis, indicating that PstS is the only CtpL Pi-shuttle. Chemotaxis mechanisms based on indirect ligand recognition were unambiguously identified in enterobacteria. The discovery of a similar mechanism in a different bacterial order, involving a different chemoreceptor type and chemoeffector suggests that such systems are widespread. PMID:27353565

  11. Observing Chemotaxis in Vibrio fischeri Using Soft Agar Assays in an Undergraduate Microbiology Laboratory

    Directory of Open Access Journals (Sweden)

    Cindy R. DeLoney-Marino

    2013-08-01

    Full Text Available Chemotaxis, the directed movement of cells towards or away from a chemical, is both an exciting and complicated behavior observed in many bacterial species. Attempting to adequately visualize or demonstrate the chemotaxic response of bacteria in the classroom is difficult at best, with good models to illustrate the concept lacking. The BSL-1 marine bacterium Vibrio fischeri (a.k.a. Aliivibrio fischeri is easy to culture, making it an ideal candidate for experiments in an undergraduate microbiology course. A number of chemoattractants for V. fischeri have been identified, including a variety of sugars, nucleosides, and amino acids (1, 2. Below presents how the soft agar-based chemotaxis assay can be implemented in the undergraduate laboratory. As bacterial cells migrate towards one or more attractants in soft agar, students can directly observe the chemotaxic behavior of V. fischeri without the need to learn complicated techniques or use specialized equipment. Once the bands of bacterial cells are observed, the migration can then be disrupted by the addition of excess attractant to the soft agar, thereby visualizing what happens once cells are no longer in a gradient of attractant. In addition, soft agar plates lacking attractants can be used to visualize the random movements of bacterial cells that are non-chemotaxing. These exercises can be used in the microbiology laboratory to help students understand the complex behavior of bacterial chemotaxis.

  12. Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix.

    Science.gov (United States)

    Stout, David A; Toyjanova, Jennet; Franck, Christian

    2015-01-01

    The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis. PMID:26131645

  13. A population-level model from the microscopic dynamics in Escherichia coli chemotaxis via Langevin approximation

    International Nuclear Information System (INIS)

    Recent extensive studies of Escherichia coli (E. coli) chemotaxis have achieved a deep understanding of its microscopic control dynamics. As a result, various quantitatively predictive models have been developed to describe the chemotactic behavior of E. coli motion. However, a population-level partial differential equation (PDE) that rationally incorporates such microscopic dynamics is still insufficient. Apart from the traditional Keller–Segel (K–S) equation, many existing population-level models developed from the microscopic dynamics are integro-PDEs. The difficulty comes mainly from cell tumbles which yield a velocity jumping process. Here, we propose a Langevin approximation method that avoids such a difficulty without appreciable loss of precision. The resulting model not only quantitatively reproduces the results of pathway-based single-cell simulators, but also provides new inside information on the mechanism of E. coli chemotaxis. Our study demonstrates a possible alternative in establishing a simple population-level model that allows for the complex microscopic mechanisms in bacterial chemotaxis

  14. Chemotaxis study using optical tweezers to observe the strength and directionality of forces of Leishmania amazonensis

    Science.gov (United States)

    Pozzo, Liliana d. Y.; Fontes, Adriana; de Thomaz, André A.; Barbosa, Luiz C.; Ayres, Diana C.; Giorgio, Selma; Cesar, Carlos L.

    2006-08-01

    The displacements of a dielectric microspheres trapped by an optical tweezers (OT) can be used as a force transducer for mechanical measurements in life sciences. This system can measure forces on the 50 femto Newtons to 200 pico Newtons range, of the same order of magnitude of a typical forces induced by flagellar motion. The process in which living microorganisms search for food and run away from poison chemicals is known is chemotaxy. Optical tweezers can be used to obtain a better understanding of chemotaxy by observing the force response of the microorganism when placed in a gradient of attractors and or repelling chemicals. This report shows such observations for the protozoa Leishmania amazomenzis, responsible for the leishmaniasis, a serious tropical disease. We used a quadrant detector to monitor the movement of the protozoa for different chemicals gradient. This way we have been able to observe both the force strength and its directionality. The characterization of the chemotaxis of these parasites can help to understand the infection mechanics and improve the diagnosis and the treatments employed for this disease.

  15. Moment-flux models for bacterial chemotaxis in large signal gradients.

    Science.gov (United States)

    Xue, Chuan; Yang, Xige

    2016-10-01

    Chemotaxis is a fundamental process in the life of many prokaryotic and eukaryotic cells. Chemotaxis of bacterial populations has been modeled by both individual-based stochastic models that take into account the biochemistry of intracellular signaling, and continuum PDE models that track the evolution of the cell density in space and time. Continuum models have been derived from individual-based models that describe intracellular signaling by a system of ODEs. The derivations rely on quasi-steady state approximations of the internal ODE system. While this assumption is valid if cell movement is subject to slowly changing signals, it is often violated if cells are exposed to rapidly changing signals. In the latter case current continuum models break down and do not match the underlying individual-based model quantitatively. In this paper, we derive new PDE models for bacterial chemotaxis in large signal gradients that involve not only the cell density and flux, but also moments of the intracellular signals as a measure of the deviation of cell's internal state from its steady state. The derivation is based on a new moment closure method without calling the quasi-steady state assumption of intracellular signaling. Numerical simulations suggest that the resulting model matches the population dynamics quantitatively for a much larger range of signals. PMID:26922437

  16. Chemotaxis for enhanced immobilization of Escherichia coli and Legionella pneumophila on biofunctionalized surfaces of GaAs.

    Science.gov (United States)

    Hassen, Walid M; Sanyal, Hashimita; Hammood, Manar; Moumanis, Khalid; Frost, Eric H; Dubowski, Jan J

    2016-06-01

    The authors have investigated the effect of chemotaxis on immobilization of bacteria on the surface of biofunctionalized GaAs (001) samples. Escherichia coli K12 bacteria were employed to provide a proof-of-concept of chemotaxis-enhanced bacterial immobilization, and then, these results were confirmed using Legionella pneumophila. The recognition layer was based on a self-assembled monolayer of thiol functionalized with specific antibodies directed toward E. coli or L. pneumophila, together with the enzyme beta-galactosidase (β-gal). The authors hypothesized that this enzyme together with its substrate lactose would produce a gradient of glucose which would attract bacteria toward the biochip surface. The chemotaxis effect was monitored by comparing the number of bacteria bound to the biochip surface with and without attractant. The authors have observed that β-gal plus lactose enhanced the immobilization of bacteria on our biochips with a higher effect at low bacterial concentrations. At 100 and 10 bacteria/ml, respectively, for E. coli and L. pneumophila, the authors observed up to 11 and 8 times more bacteria bound to biochip surfaces assisted with the chemotaxis effect in comparison to biochips without chemotaxis. At 10(4) bacteria/ml, the immobilization enhancement rate did not exceed two times. PMID:27098616

  17. Genetic Circuits and Chemotaxis Induced Bacterial Cloning on Media Plate

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    2016-03-01

    Full Text Available Objective: Synthetic biology demonstrates its broad application perspective in the fields of medicine, chemical synthesis, and the production of energy. Methods: The character that E. coli responding to the stimulus is named as chemo taxis which has widely applications such as measurement efficiency of RBS and promoter, suicide mechanism, oscillation timer etc. Results: A circuit to control the motility of E. coli (run or tumble and form the patterns such as conic curves was constructed. The strength of the promoter and the efficiency of RBS were successfully characterized by using the circuit and chemo taxis that can be used to characterize most of the promoters, the RBS efficiency, terminator efficiency and expression strength of target genes etc. A new suicide mechanism, utilizing the hyperosmotic pressure, was built to induce the growth of E. coli Pattern model is the fundamental force in the coordination of multicellular behavior in the bacterial community or a large complex system. Conclusion: The sources of stress (such as sodium chloride and sucrose be to generate hypertonic very cheap, convenient and environmentally friendly while antibiotics are expensive and have a bad effect on the environment because of drug-resistant microorganisms.

  18. Response coefficient analysis of E. coli chemotaxis to parametric perturbations under the influence of noise

    Directory of Open Access Journals (Sweden)

    Pratap R Patnaik

    2012-08-01

    Full Text Available Escherichia coli and other bacteria navigating through ‘open’ environments are under the impact of noise from the environment and from within the cells. This generates fluctuations in the kinetic parameters that characterize the intra-cellular reactions of the chemosensory network, thus affecting the chemotaxis of the cells. This aspect has been studied here for E. coli synthesizing recombinant glucoamylase in a continuous-flow microreactor. Response coefficient analysis (RCA was applied to a new four-parameter model of the chemotaxis of E. coli. The model considered two types of responses of the cells – linear and adaptive – and two rates of movement of the chemoattractant – slow and fast. Some cells at each position in the microreactor were considered to be moving to the left, some to the right and others in a tumbling state. Striking similarities and differences were observed between the different types of cells, between linear and adaptive responses, and between the kinetic responses to a slow-moving and a fast-moving chemoattractant distribution. One salient observation was that the response coefficients of the left-moving and right-moving sub-populations were mirror images of each other. Tumbling cells either had intermediate characteristics in some situations, as might be expected, or, in other circumstances, resembled the left-moving cells more than they corresponded to the right-moving bacteria. Under certain conditions, cells with normal linear responses exhibited pseudo-adaptive kinetic behavior. Such unexpected observations have been explained. The results offer new insights into possible quantitative effects of environmental noise on the chemotaxis of E. coli and other bacteria.

  19. Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth.

    Directory of Open Access Journals (Sweden)

    Roeland M H Merks

    Full Text Available Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully formed blood vessels organize into a vessel network (vasculogenesis, or by sprouting or splitting of existing blood vessels (angiogenesis. Although they are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting. We present a cell-based, Glazier-Graner-Hogeweg model (also called Cellular Potts Model simulation of the initial patterning before the vascular cords form lumens, based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller-Segel model, chemotaxis by itself causes cells to aggregate into isolated clusters. However, including experimentally observed VE-cadherin-mediated contact inhibition of chemotaxis in the simulation causes randomly distributed cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results. Cells at the surfaces of cell clusters attempting to migrate to the centers of the clusters produce a buckling instability. In a model variant that eliminates the surface-normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattractant and as an inhibitor of pseudopod extension. Both mechanisms would also apply if force transmission through the extracellular matrix rather than chemical signaling mediated cell-cell interactions. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual patterning instabilities.

  20. Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum

    OpenAIRE

    Hsu, Ming-Jen; Lee, Shiuh-Sheng; Lee, Sho Tone; Lin, Wan-Wan

    2003-01-01

    The polysaccharide from Ganoderma lucidum (PS-G) has been reported to enhance immune responses and to elicit antitumor effects. In our previous study, we found that PS-G efficiently inhibited spontaneously and Fas-enhanced neutrophil apoptosis when cultured in vitro. Since phagocytosis and chemotaxis play essential roles in host defense mediated by neutrophils, it is of great interest to know the effect of PS-G on these two cell functions, and the molecular events leading to these actions.Usi...

  1. The chemical-in-plug bacterial chemotaxis assay is prone to false positive responses

    Directory of Open Access Journals (Sweden)

    Ward Mandy J

    2010-03-01

    Full Text Available Abstract Background Chemical-in-plug assays are commonly used to study bacterial chemotaxis, sometimes in the absence of stringent controls. Results We report that non-chemotactic and non-motile mutants in two distinct bacterial species (Shewanella oneidensis and Helicobacter pylori show apparent zones of accumulation or clearing around test plugs containing potential attractants or repellents, respectively. Conclusions Our results suggest that the chemical-in-plug assay should be used with caution, that non-motile or non-chemotactic mutants should be employed as controls, and that results should be confirmed with other types of assays.

  2. Transducer Like Proteins of Campylobacter jejuni 81-176: Role in chemotaxis and colonization of the chicken gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Gireesh eRajashekara

    2015-05-01

    Full Text Available Transducer Like Proteins (Tlps, also known as Methyl accepting chemotaxis proteins (MCP, enable enteric pathogens to respond to changing nutrient levels in the environment by mediating taxis towards or away from specific chemoeffector molecules such as nutrients. Despite recent advances in the characterization of chemotaxis responses in Campylobacter jejuni, the impact of Tlps on the adaptation of this pathogen to disparate niches and hosts is not fully characterized. The latter is particularly evident in the case of C. jejuni 81-176, a strain that is known to be highly invasive. Furthermore, the cytoplasmic group C Tlps (Tlp5, 6, and 8 was not extensively evaluated. Here, we investigated the role of C. jejuni 81-176 Tlps in chemotaxis towards various substrates, biofilm formation, in vitro interaction with human intestinal cells, and chicken colonization. We found that the ∆tlp6 and ∆tlp10 mutants exhibited decreased chemotaxis towards aspartate whereas the ∆tlp6 mutant displayed a decreased chemotaxis towards Tri-Carboxylic Acid (TCA cycle intermediates such as pyruvate, isocitrate, and succinate. Our findings also corroborated that more than one Tlp is involved in mediating chemotaxis towards the same nutrient. The deletion of tlps affected important phenotypes such as motility, biofilm formation, and invasion of human intestinal epithelial cells (INT-407. The ∆tlp8 mutant displayed increased motility in soft agar and showed decreased biofilm formation. The ∆tlp8 and ∆tlp9 mutants were significantly defective in invasion in INT-407 cells. The ∆tlp10 mutant was defective in colonization of the chicken proximal and distal gastrointestinal tract, while the ∆tlp6 and ∆tlp8 mutants showed reduced colonization of the duodenum and jejunum. Our results highlight the importance of Tlps in C. jejuni’s adaptation and pathobiology.

  3. Borrelia burgdorferi CheD Promotes Various Functions in Chemotaxis and the Pathogenic Life Cycle of the Spirochete.

    Science.gov (United States)

    Moon, Ki Hwan; Hobbs, Gerry; Motaleb, M A

    2016-06-01

    Borrelia burgdorferi possesses a sophisticated chemotaxis signaling system; however, the roles of the majority of the chemotaxis proteins in the infectious life cycle have not yet been demonstrated. Specifically, the role of CheD during host colonization has not been demonstrated in any bacterium. Here, we systematically characterized the B. burgdorferi CheD homolog using genetics and biochemical and mouse-tick-mouse infection cycle studies. Bacillus subtilis CheD plays an important role in chemotaxis by deamidation of methyl-accepting chemotaxis protein receptors (MCPs) and by increasing the receptor kinase activity or enhancing CheC phosphatase activity, thereby regulating the levels of the CheY response regulator. Our biochemical analysis indicates that B. burgdorferi CheD significantly enhances CheX phosphatase activity by specifically interacting with the phosphatase. Moreover, CheD specifically binds two of the six MCPs, indicating that CheD may also modulate the receptor proteins. Although the motility of the cheD mutant cells was indistinguishable from that of the wild-type cells, the mutant did exhibit reduced chemotaxis. Importantly, the mutant showed significantly reduced infectivity in C3H/HeN mice via needle inoculation. Mouse-tick-mouse infection assays indicated that CheD is dispensable for acquisition or transmission of spirochetes; however, the viability of cheD mutants in ticks is marginally reduced compared to that of the wild-type or complemented cheD spirochetes. These data suggest that CheD plays an important role in the chemotaxis and pathogenesis of B. burgdorferi We propose potential connections between CheD, CheX, and MCPs and discuss how these interactions play critical roles during the infectious life cycle of the spirochete. PMID:27021244

  4. Computational modeling reveals that a combination of chemotaxis and differential adhesion leads to robust cell sorting during tissue patterning.

    Science.gov (United States)

    Tan, Rui Zhen; Chiam, Keng-Hwee

    2014-01-01

    Robust tissue patterning is crucial to many processes during development. The "French Flag" model of patterning, whereby naïve cells in a gradient of diffusible morphogen signal adopt different fates due to exposure to different amounts of morphogen concentration, has been the most widely proposed model for tissue patterning. However, recently, using time-lapse experiments, cell sorting has been found to be an alternative model for tissue patterning in the zebrafish neural tube. But it remains unclear what the sorting mechanism is. In this article, we used computational modeling to show that two mechanisms, chemotaxis and differential adhesion, are needed for robust cell sorting. We assessed the performance of each of the two mechanisms by quantifying the fraction of correct sorting, the fraction of stable clusters formed after correct sorting, the time needed to achieve correct sorting, and the size variations of the cells having different fates. We found that chemotaxis and differential adhesion confer different advantages to the sorting process. Chemotaxis leads to high fraction of correct sorting as individual cells will either migrate towards or away from the source depending on its cell type. However after the cells have sorted correctly, there is no interaction among cells of the same type to stabilize the sorted boundaries, leading to cell clusters that are unstable. On the other hand, differential adhesion results in low fraction of correct clusters that are more stable. In the absence of morphogen gradient noise, a combination of both chemotaxis and differential adhesion yields cell sorting that is both accurate and robust. However, in the presence of gradient noise, the simple combination of chemotaxis and differential adhesion is insufficient for cell sorting; instead, chemotaxis coupled with delayed differential adhesion is required to yield optimal sorting. PMID:25302949

  5. The Mechanism and Usage for Enhanced Oil Recovery by Chemotaxis of Bacterium BS2

    Institute of Scientific and Technical Information of China (English)

    LiYiqian; JingGuicheng; GaoShusheng; XungWei

    2005-01-01

    Due to its chemotaxis, the motion ability of bacterium BS2 is very strong, and under the microscope, the distribution grads of bacterium concentration can be seen at the oil-water interface. During the experiments in glass box, it can be observed, with eyes, because of the chemotaxis, that muddy gets thicker and thicker at the interface gradually, and it is measured there, from sampling, that the bacterium concentration is 109 cells/mL, pH value 4.4 and the concentration of bio-surfactant 2.87%; The microbial oil-displacement experiments are carried out in emulational network models, and the oil-displacement mechanism by the bacterium and its metabolizing production is studied. And, during oil-displacement experiments in the gravel-input glass models, because of the profile control of thalli and the production, the sweep area of subsequent waterflood becomes wider, which can be seen with eyes and the recovery is enhanced by 13.6%. Finally, the successful field test is introduced in brief: the ratio of response producers is 85.7%, and the water-cut degrades by 6.4%, while 20038t oil has increased in accumulative total in 2 years.

  6. Marangoni-driven chemotaxis, chemotactic collapse, and the Keller-Segel equation

    Science.gov (United States)

    Shelley, Michael; Masoud, Hassan

    2013-11-01

    Almost by definition, chemotaxis involves the biased motion of motile particles along gradients of a chemical concentration field. Perhaps the most famous model for collective chemotaxis in mathematical biology is the Keller-Segel model, conceived to describe collective aggregation of slime mold colonies in response to an intrinsically produced, and diffusing, chemo-attractant. Heavily studied, particularly in 2D where the system is ``super-critical'', it has been proved that the KS model can develop finite-time singularities - so-called chemotactic collapse - of delta-function type. Here, we study the collective dynamics of immotile particles bound to a 2D interface above a 3D fluid. These particles are chemically active and produce a diffusing field that creates surface-tension gradients along the surface. The resultant Marangoni stresses create flows that carry the particles, possibly concentrating them. Remarkably, we show that this system involving 3D diffusion and fluid dynamics, exactly yields the 2D Keller-Segel model for the surface-flow of active particles. We discuss the consequences of collapse on the 3D fluid dynamics, and generalizations of the fluid-dynamical model.

  7. Histamine H3 receptor in primary mouse microglia inhibits chemotaxis, phagocytosis, and cytokine secretion.

    Science.gov (United States)

    Iida, Tomomitsu; Yoshikawa, Takeo; Matsuzawa, Takuro; Naganuma, Fumito; Nakamura, Tadaho; Miura, Yamato; Mohsen, Attayeb S; Harada, Ryuichi; Iwata, Ren; Yanai, Kazuhiko

    2015-07-01

    Histamine is a physiological amine which initiates a multitude of physiological responses by binding to four known G-protein coupled histamine receptor subtypes as follows: histamine H1 receptor (H1 R), H2 R, H3 R, and H4 R. Brain histamine elicits neuronal excitation and regulates a variety of physiological processes such as learning and memory, sleep-awake cycle and appetite regulation. Microglia, the resident macrophages in the brain, express histamine receptors; however, the effects of histamine on critical microglial functions such as chemotaxis, phagocytosis, and cytokine secretion have not been examined in primary cells. We demonstrated that mouse primary microglia express H2 R, H3 R, histidine decarboxylase, a histamine synthase, and histamine N-methyltransferase, a histamine metabolizing enzyme. Both forskolin-induced cAMP accumulation and ATP-induced intracellular Ca(2+) transients were reduced by the H3 R agonist imetit but not the H2 R agonist amthamine. H3 R activation on two ubiquitous second messenger signalling pathways suggests that H3 R can regulate various microglial functions. In fact, histamine and imetit dose-dependently inhibited microglial chemotaxis, phagocytosis, and lipopolysaccharide (LPS)-induced cytokine production. Furthermore, we confirmed that microglia produced histamine in the presence of LPS, suggesting that H3 R activation regulate microglial function by autocrine and/or paracrine signalling. In conclusion, we demonstrate the involvement of histamine in primary microglial functions, providing the novel insight into physiological roles of brain histamine. PMID:25754956

  8. CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a

    Directory of Open Access Journals (Sweden)

    Rachel Vaivoda

    2015-01-01

    Full Text Available CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4. CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9–2.25-fold in knockout cells compared to wild-type (P < 0.01. This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies.

  9. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  10. Effects of thalidomide on neutrophil respiratory burst, chemotaxis, and transmigration of cytokine- and endotoxin-activated endothelium.

    Science.gov (United States)

    Dunzendorfer, S; Schratzberger, P; Reinisch, N; Kähler, C M; Wiedermann, C J

    1997-11-01

    Vascular endothelium activated by endotoxin and cytokines plays an important role in organ inflammation and blood leukocyte recruitment. Neutrophils, which are a homogeneous population of effector cells, are rapidly attracted in large numbers to sites of inflammation where they form an early response to infection or injury. Excessive production of various interleukins, TNF, arachidonic acid metabolites, and other substances by neutrophils and macrophages results in systemic endothelial cell injury, a fundamental problem. In the present study, we investigated in vitro the effects of thalidomide (THD) on activation of endothelial cells for enhanced transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), and interleukin-1 (IL-1). Modulation of endotoxin- and cytokine-induced neutrophil chemotaxis and respiratory burst by THD were also studied. Treatment of HUVEC with THD in combination with LPS, TNF, and IL-1, respectively, antagonized LPS-activated transmigration of neutrophils but stimulated the effects of TNF and IL-1. All of the agents used-THD, LPS, TNF, and IL-1-inhibited neutrophil chemotaxis. Addition of THD to the neutrophils had no effect on LPS-inhibited chemotaxis whereas the TNF- and IL-1-induced chemotaxis was modulated in a bimodal manner. However, THD failed to influence neutrophil respiratory burst activity. Results demonstrate that THD differentially affects mediator-induced activation of HUVEC and neutrophils. PMID:9402031

  11. Induction of chemotaxis to sodium chloride and diacetyl and thermotaxis defects by microcystin-LR exposure in nematode Caenorhabditis elegans

    Institute of Scientific and Technical Information of China (English)

    LI Yunhui; YE Huayue; DU Min; ZHANG Yanfen; YE Boping; PU Yuepu; WANG Dayong

    2009-01-01

    Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin (MC)-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was explored as a model to study the neurotoxicity. In the present study, we provided evidence to indicate the neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure to C. elegans. As a result, higher concentrations of MC-LR caused significantly severe defects of chemotaxis to NaC1 and diacetyl, and thermotaxis. The neurotoxicity on chemotaxis to NaCl and diacetyl, and thennotaxis from MC-LR exposure might be largely mediated by the damage on the corresponding sensory neurons (ASE, AWA, and AFD) and interneuron AIY. The expression levels of che-1 and odr-7 were significantly decreased (P<0.01) in animals exposed to MC-LR at concentrations lower than 10 μg/L, whereas the expression levels of ttx-1 and ttx-3 could be significantly (P<0.01) lowered in animals even exposed to 1 μg/L of MC-LR. Moreover, both the chemotaxis to NaCl and diacetyl and the thermotaxis were more significantly reduced m MC-LR exposed mutants of che-1(p674), odr-7(ky4), ttx-1(p767), and ttx-3(ks5) than those in exposed wild-type N2 animals at the same concentrations.

  12. Structural and Functional Characterization of Two Alternative Splicing Variants of Mouse Endothelial Cell-Specific Chemotaxis Regulator (ECSCR

    Directory of Open Access Journals (Sweden)

    Yongchang Chang

    2012-04-01

    Full Text Available Endothelial cells (ECs that line the lumen of blood vessels are important players in blood vessel formation, and EC migration is a key component of the angiogenic process. Thus, identification of genes that are specifically or preferentially expressed in vascular ECs and in-depth understanding of their biological functions may lead to discovery of new therapeutic targets. We have previously reported molecular characterization of human endothelial cell-specific molecule 2 (ECSM2/endothelial cell-specific chemotaxis regulator (ECSCR. In the present study, we cloned two mouse full-length cDNAs by RT-PCR, which encode two putative ECSCR isoform precursors with considerable homology to the human ECSCR. Nucleotide sequence and exon-intron junction analyses suggested that they are alternative splicing variants (ECSCR isoform-1 and -2, differing from each other in the first and second exons. Quantitative RT-PCR results revealed that isoform-2 is the predominant form, which was most abundant in heart, lung, and muscles, and moderately abundant in uterus and testis. In contrast, the expression of isoform-1 seemed to be more enriched in testis. To further explore their potential cellular functions, we expressed GFP- and FLAG-tagged ECSCR isoforms, respectively, in an ECSCR deficient cell line (HEK293. Interestingly, the actual sizes of either ECSCR-GFP or -FLAG fusion proteins detected by immunoblotting are much larger than their predicted sizes, suggesting that both isoforms are glycoproteins. Fluorescence microscopy revealed that both ECSCR isoforms are localized at the cell surface, which is consistent with the structural prediction. Finally, we performed cell migration assays using mouse endothelial MS1 cells overexpressing GFP alone, isoform-1-GFP, and isoform-2-GFP, respectively. Our results showed that both isoforms significantly inhibited vascular epidermal growth factor (VEGF-induced cell migration. Taken together, we have provided several lines

  13. Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Eitaro Aihara

    2014-07-01

    Full Text Available Helicobacter pylori (H. pylori is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1 significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB or chemotaxis (ΔcheY. ΔmotB (10(6 failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6 colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites

  14. Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils

    Science.gov (United States)

    Fu, Chia-Hsiang; Tsai, Wan-Chun; Lee, Ta-Jen; Huang, Chi-Che; Chang, Po-Hung; Su Pang, Jong-Hwei

    2016-01-01

    IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague–Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis. PMID:27275740

  15. Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients

    DEFF Research Database (Denmark)

    Hjortø, Gertrud Malene; Olsen, Mark Holm; Svane, Inge Marie; Larsen, Niels Bent

    2015-01-01

    relevant to tissue models by two-photon polymerization of linear channel constructs with cross-sections from 10 × 10 μm2 to 20 × 20 μm2 inside commercially available chemotaxis analysis chips. Faster directed migration was observed with decreasing channel dimensions despite substantial cell deformation in...... velocity dependence on channel cross-section. However, added effects due to spatial confinement could not be excluded. The design freedom offered by two-photon polymerization was exploited to minimize the accentuated concentration gradients in cell-blocked channels by introducing “venting slits” to the......2 channel. This result agrees with model predictions of very small concentration gradient variations in slitted channels, thus indicating a strong influence of the concentration gradient steepness, not the channel size, on the directed migration velocity....

  16. Individual-based models for bacterial chemotaxis in the diffusion asymptotics

    CERN Document Server

    Rousset, Mathias

    2011-01-01

    We discuss velocity-jump models for chemotaxis of bacteria with an internal state that allows the velocity jump rate to depend on the memory of the chemoattractant concentration along their path of motion. Using probabilistic techniques, we provide a pathwise result that shows that the considered process converges to an advection-diffusion process in the (long-time) diffusion limit. We also (re-)prove using the same approach that the same limiting equation arises for a related, simpler process with direct sensing of the chemoattractant gradient. Additionally, we propose a time discretization technique that retains these diffusion limits exactly, i.e., without error that depends on the time discretization. In the companion paper \\cite{variance}, these results are used to construct a coupling technique that allows numerical simulation of the process with internal state with asymptotic variance reduction, in the sense that the variance vanishes in the diffusion limit.

  17. Simulating individual-based models of bacterial chemotaxis with asymptotic variance reduction

    CERN Document Server

    Rousset, Mathias

    2011-01-01

    We discuss variance reduced simulations for an individual-based model of chemotaxis of bacteria with internal dynamics. The variance reduction is achieved via a coupling of this model with a simpler process in which the internal dynamics has been replaced by a direct gradient sensing of the chemoattractants concentrations. In the companion paper \\cite{limits}, we have rigorously shown, using a pathwise probabilistic technique, that both processes converge towards the same advection-diffusion process in the diffusive asymptotics. In this work, a direct coupling is achieved between paths of individual bacteria simulated by both models, by using the same sets of random numbers in both simulations. This coupling is used to construct a hybrid scheme with reduced variance. We first compute a deterministic solution of the kinetic density description of the direct gradient sensing model; the deviations due to the presence of internal dynamics are then evaluated via the coupled individual-based simulations. We show th...

  18. Macroscopic dynamics of biological cells interacting via chemotaxis and direct contact

    CERN Document Server

    Lushnikov, Pavel M; Alber, Mark

    2008-01-01

    A connection is established between discrete stochastic model describing microscopic motion of fluctuating cells, and macroscopic equations describing dynamics of cellular density. Cells move towards chemical gradient (process called chemotaxis) with their shapes randomly fluctuating. Nonlinear diffusion equation is derived from microscopic dynamics in dimensions one and two using excluded volume approach. Nonlinear diffusion coefficient depends on cellular volume fraction and it is demonstrated to prevent collapse of cellular density. A very good agreement is shown between Monte Carlo simulations of the microscopic Cellular Potts Model and numerical solutions of the macroscopic equations for relatively large cellular volume fractions. Combination of microscopic and macroscopic models were used to simulate growth of structures similar to early vascular networks.

  19. Chemotaxis of horse polymorphonuclear leukocytes to N-formyl-L-methionyl-L-leucyl-L-phenylalanine.

    Science.gov (United States)

    Zinkl, J G; Brown, P D

    1982-04-01

    Horse polymorphonuclear leukocytes (PMN) isolated from horse blood by sedimentation and isotonic lysis and having about 25% accompanying lymphocytes were as effective at chemotaxis as nearly pure PMN isolated by density gradient techniques. N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), used as a representative of the formylmethionyl peptides (produced by prokaryocytic organisms), was effective as a chemoattractant only at the high concentration of 10(-4) M. When serum was preincubated with FMLP at concentrations as low as 10(-8) M, the serum attracted horse PMN. This activity was not generated when heat-inactivated (56 to 60 C for 30 minutes) serum was used. A combination of FMLP and zymosan was no more effective than zymosan alone in generating serum chemoattractants. The results of this study indicate that the FMLP is a weak chemoattractant for horse PMN, but that FMLP has the capability similar to that of zymosan to activate complement to produce PMN chemoattractants. PMID:7073083

  20. The stochastic dance of circling sperm cells: sperm chemotaxis in the plane

    International Nuclear Information System (INIS)

    Biological systems such as single cells must function in the presence of fluctuations. It has been shown in a two-dimensional experimental setup that sea urchin sperm cells move toward a source of chemoattractant along planar trochoidal swimming paths, i.e. drifting circles. In these experiments, a pronounced variability of the swimming paths is observed. We present a theoretical description of sperm chemotaxis in two dimensions which takes fluctuations into account. We derive a coarse-grained theory of stochastic sperm swimming paths in a concentration field of chemoattractant. Fluctuations enter as multiplicative noise in the equations for the sperm swimming path. We discuss the stochastic properties of sperm swimming and predict a concentration-dependence of the effective diffusion constant of sperm swimming which could be tested in experiments.

  1. Intra-amoeba multiplication induces chemotaxis and biofilm colonization and formation for Legionella.

    Directory of Open Access Journals (Sweden)

    Renaud Bigot

    Full Text Available Legionella pneumophila, a facultative intracellular bacterium, is the causative agent of legionellosis. In the environment this pathogenic bacterium colonizes the biofilms as well as amoebae, which provide a rich environment for the replication of Legionella. When seeded on pre-formed biofilms, L. pneumophila was able to establish and survive and was only found at the surface of the biofilms. Different phenotypes were observed when the L. pneumophila, used to implement pre-formed biofilms or to form mono-species biofilms, were cultivated in a laboratory culture broth or had grown intracellulary within the amoeba. Indeed, the bacteria, which developed within the amoeba, formed clusters when deposited on a solid surface. Moreover, our results demonstrate that multiplication inside the amoeba increased the capacity of L. pneumophila to produce polysaccharides and therefore enhanced its capacity to establish biofilms. Finally, it was shown that the clusters formed by L. pneumophila were probably related to the secretion of a chemotaxis molecular agent.

  2. Intra-amoeba multiplication induces chemotaxis and biofilm colonization and formation for Legionella.

    Science.gov (United States)

    Bigot, Renaud; Bertaux, Joanne; Frere, Jacques; Berjeaud, Jean-Marc

    2013-01-01

    Legionella pneumophila, a facultative intracellular bacterium, is the causative agent of legionellosis. In the environment this pathogenic bacterium colonizes the biofilms as well as amoebae, which provide a rich environment for the replication of Legionella. When seeded on pre-formed biofilms, L. pneumophila was able to establish and survive and was only found at the surface of the biofilms. Different phenotypes were observed when the L. pneumophila, used to implement pre-formed biofilms or to form mono-species biofilms, were cultivated in a laboratory culture broth or had grown intracellulary within the amoeba. Indeed, the bacteria, which developed within the amoeba, formed clusters when deposited on a solid surface. Moreover, our results demonstrate that multiplication inside the amoeba increased the capacity of L. pneumophila to produce polysaccharides and therefore enhanced its capacity to establish biofilms. Finally, it was shown that the clusters formed by L. pneumophila were probably related to the secretion of a chemotaxis molecular agent. PMID:24205008

  3. The stochastic dance of circling sperm cells: sperm chemotaxis in the plane

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, B M; Juelicher, F [Max Planck Institute for the Physics of Complex Systems, Noethnitzer Strasse 38, 01187 Dresden (Germany)], E-mail: ben@pks.mpg.de, E-mail: julicher@pks.mpg.de

    2008-12-15

    Biological systems such as single cells must function in the presence of fluctuations. It has been shown in a two-dimensional experimental setup that sea urchin sperm cells move toward a source of chemoattractant along planar trochoidal swimming paths, i.e. drifting circles. In these experiments, a pronounced variability of the swimming paths is observed. We present a theoretical description of sperm chemotaxis in two dimensions which takes fluctuations into account. We derive a coarse-grained theory of stochastic sperm swimming paths in a concentration field of chemoattractant. Fluctuations enter as multiplicative noise in the equations for the sperm swimming path. We discuss the stochastic properties of sperm swimming and predict a concentration-dependence of the effective diffusion constant of sperm swimming which could be tested in experiments.

  4. A Role for the Chemokine Receptor CCR6 in Mammalian Sperm Motility and Chemotaxis

    Science.gov (United States)

    Caballero-Campo, Pedro; Buffone, Mariano G.; Benencia, Fabian; Conejo-García, José R.; Rinaudo, Paolo F.; Gerton, George L.

    2013-01-01

    Although recent evidence indicates that several chemokines and defensins, well-known as inflammatory mediators, are expressed in the male and female reproductive tracts, the location and functional significance of chemokine networks in sperm physiology and sperm reproductive tract interactions are poorly understood. To address this deficiency in our knowledge, we examined the expression and function in sperm of CCR6, a receptor common to several chemoattractant peptides, and screened several reproductive tract fluids for the presence of specific ligands. CCR6 protein is present in mouse and human sperm and mainly localized in the sperm tail with other minor patterns in sperm from mice (neck and acrosomal region) and men (neck and midpiece regions). As expected from the protein immunoblotting and immunofluorescence results, mouse Ccr6 mRNA is expressed in the testis. Furthermore, the Defb29 mRNA encoding the CCR6 ligand, β-defensin DEFB29, is expressed at high levels in the epididymis. As determined by protein chip analysis, several chemokines (including some that act through CCR6, such as CCL20/MIP-3α (formerly Macrophage Inflammatory Protein 3α) and protein hormones were present in human follicular fluid, endometrial secretions, and seminal plasma. In functional chemotaxis assays, capacitated human sperm exhibited a directional movement towards CCL20, and displayed modifications in motility parameters. Our data indicate that chemokine ligand/receptor interactions in the male and female genital tracts promote sperm motility and chemotaxis under non-inflammatory conditions. Therefore, some of the physiological reactions mediated by CCR6 ligands in male reproduction extend beyond a pro-inflammatory response and might find application in clinical reproduction and/or contraception. PMID:23765988

  5. The photosensor protein Ppr of Rhodocista centenaria is linked to the chemotaxis signalling pathway

    Directory of Open Access Journals (Sweden)

    Kiefer Dorothee

    2010-11-01

    Full Text Available Abstract Background Rhodocista centenaria is a phototrophic α-proteobacterium exhibiting a phototactic behaviour visible as colony movement on agar plates directed to red light. As many phototrophic purple bacteria R. centenaria possesses a soluble photoactive yellow protein (Pyp. It exists as a long fusion protein, designated Ppr, consisting of three domains, the Pyp domain, a putative bilin binding domain (Bbd and a histidine kinase domain (Pph. The Ppr protein is involved in the regulation of polyketide synthesis but it is still unclear, how this is connected to phototaxis and chemotaxis. Results To elucidate the possible role of Ppr and Pph in the chemotactic network we studied the interaction with chemotactic proteins in vitro as well as in vivo. Matrix-assisted coelution experiments were performed to study the possible communication of the different putative binding partners. The kinase domain of the Ppr protein was found to interact with the chemotactic linker protein CheW. The formation of this complex was clearly ATP-dependent. Further results indicated that the Pph histidine kinase domain and CheW may form a complex with the chemotactic kinase CheAY suggesting a role of Ppr in the chemotaxis signalling pathway. In addition, when Ppr or Pph were expressed in Escherichia coli, the chemotactic response of the cells was dramatically affected. Conclusions The Ppr protein of Rhodocista centenaria directly interacts with the chemotactic protein CheW. This suggests a role of the Ppr protein in the regulation of the chemotactic response in addition to its role in chalcone synthesis.

  6. LPS responsiveness and neutrophil chemotaxis in vivo require PMN MMP-8 activity.

    Directory of Open Access Journals (Sweden)

    Angus M Tester

    Full Text Available We identify matrix metalloproteinase (MMP-8, the polymorphonuclear (PMN leukocyte collagenase, as a critical mediator initiating lipopolysaccharide (LPS-responsiveness in vivo. PMN infiltration towards LPS is abrogated in Mmp8-null mice. MMP-8 cleaves LPS-induced CXC chemokine (LIX at Ser(4-Val(5 and Lys(79-Arg(80. LIX bioactivity is increased upon N-terminal cleavage, enhancing intracellular calcium mobilization and chemotaxis upon binding its cognate receptor, CXCR2. As there is no difference in PMN chemotaxis in Mmp8-null mice compared with wild-type mice towards synthetic analogues of MMP-8-cleaved LIX, MMP-8 is not essential for extravasation or cell migration in collagenous matrices in vivo. However, with biochemical redundancy between MMPs 1, 2, 9, and 13, which also cleave LIX at position 4 approximately 5, it was surprising to observe such a markedly reduced PMN infiltration towards LPS and LIX in Mmp8-/- mice. This lack of physiological redundancy in vivo identifies MMP-8 as a key mediator in the regulation of innate immunity. Comparable results were found with CXCL8/IL-8 and CXCL5/ENA-78, the human orthologues of LIX. MMP-8 cleaves CXCL8 at Arg(5-Ser(6 and at Val(7-Leu(8 in CXCL5 to activate respective chemokines. Hence, rather than collagen, these PMN chemoattractants are important MMP-8 substrates in vivo; PMN-derived MMP-8 cleaves and activates LIX to execute an in cis PMN-controlled feed-forward mechanism to orchestrate the initial inflammatory response and promote LPS responsiveness in tissue.

  7. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  8. Inhibitory effects of cryptoporus polysaccharide on airway constriction, eosinophil release, and chemotaxis in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan ZHAO; Qiang-min XIE; Ji-qiang CHEN; Chuan-kui KE

    2004-01-01

    AIM: To study effects of cryptoporus polysaccharide (CP) on antigen-induced bronchoconstriction, eosinophil peroxidase (EPO) release in vivo, and on platelet activating factor (PAF)-induced eosinophil chemotaxis in vitro in guinea pig. METHODS: The asthma model of guinea pig was formed with ovalbumin (OVA). The changes of lung resistance (RL) and dynamic lung compliance (Cdyn), EPO level in bronchoalveolar lavage fluids (BALF) and eosinophil migration were determined. RESULTS: Pretreatment of CP at doses of 3, 9, and 27 mg/kg by intragastric gavage (ig), qd for 10 d, inhibited early asthma response in a dose-dependent manner. Inhibitory rates of mean increase value from 1 to 30 min of RL were 34.8 %, 74.4 % (P<0.05), and 79.6 % (P<0.05), respectively. Inhibitory rate of mean reduction value of Cdyn were 22.9 %, 40.5 % (P<0.01), and 66.5 % (P<0.01), respectively.Pretreatment of CP at doses of 3, 9, and 27 mg/kg also inhibited late asthma response, and the reduction of EPO level in BALF were 3.1%, 16.9 % (P<0.01), and 20.1% (P<0.01), respectively. The inhibitory rates of CP at concentrations of 0.13, 1.3, 13, 130 nmol/L to eosinophil migration induced by PAF were 6.8 %, 17.2 % (P<0.05),29.6 % (P<0.01), and 35.9 % (P<0.01). CONCLUSION: CP protects lung against increase of RL and reduction of Cdyn, decreases EPO level in the asthma model, and inhibits eosinophil chemotaxis induced by PAF. The results suggest that CP may be a novel antiinflammatory agent for the treatment of asthma and allergic diseases.

  9. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.

    Directory of Open Access Journals (Sweden)

    Orion D Weiner

    2006-02-01

    Full Text Available Migrating cells need to make different actin assemblies at the cell's leading and trailing edges and to maintain physical separation of signals for these assemblies. This asymmetric control of activities represents one important form of cell polarity. There are significant gaps in our understanding of the components involved in generating and maintaining polarity during chemotaxis. Here we characterize a family of complexes (which we term leading edge complexes, scaffolded by hematopoietic protein 1 (Hem-1, that organize the neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE2 complex, which mediates activation of actin polymerization by Rac, is only one member of this family. A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins. RNA interference-mediated knockdown of Hem-1-containing complexes in neutrophil-like cells: (a dramatically impairs attractant-induced actin polymerization, polarity, and chemotaxis; (b substantially weakens Rac activation and phosphatidylinositol-(3,4,5-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5-tris-phosphate/Rac/F-actin-mediated feedback circuit that organizes the leading edge; and (c prevents exclusion of activated myosin from the leading edge, perhaps by misregulating leading edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken together, these observations show that versatile Hem-1-containing complexes coordinate diverse regulatory signals at the leading edge of polarized neutrophils, including but not confined to those involving WAVE2-dependent actin polymerization.

  10. Chemotaxis and degradation of organophosphate compound by a novel moderately thermo-halo tolerant Pseudomonas sp. strain BUR11: evidence for possible existence of two pathways for degradation.

    Science.gov (United States)

    Pailan, Santanu; Saha, Pradipta

    2015-01-01

    An organophosphate (OP) degrading chemotactic bacterial strain BUR11 isolated from an agricultural field was identified as a member of Pseudomonas genus on the basis of its 16S rRNA gene sequence. The strain could utilize parathion, chlorpyrifos and their major hydrolytic intermediates as sole source of carbon for its growth and exhibited positive chemotactic response towards most of them. Optimum concentration of parathion for its growth was recorded to be 200 ppm and 62% of which was degraded within 96 h at 37 °C. Growth studies indicated the strain to be moderately thermo-halo tolerant in nature. Investigation based on identification of intermediates of parathion degradation by thin layer chromatography (TLC), high performance liquid chromatography (HPLC), gas chromatography (GC) and liquid chromatography mass spectrometry (LC-MS/MS) provided evidence for possible existence of two pathways. The first pathway proceeds via 4-nitrophenol (4-NP) while the second proceeds through formation of 4-aminoparathion (4-APar), 4-aminophenol (4-AP) and parabenzoquinone (PBQ). This is the first report of chemotaxis towards organophosphate compound by a thermo-halo tolerant bacterium. PMID:26587344

  11. p38 MAPK is involved in human neutrophil chemotaxis induced by L-amino acid oxidase from Calloselasma rhodosthoma.

    Science.gov (United States)

    Pontes, Adriana S; Setúbal, Sulamita da S; Nery, Neriane Monteiro; da Silva, Francisquinha Souza; da Silva, Silvana D; Fernandes, Carla F C; Stábeli, Rodrigo G; Soares, Andreimar M; Zuliani, Juliana P

    2016-09-01

    The action of LAAO, an L-amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, on isolated human neutrophil function was investigated. Cr-LAAO showed no toxicity on neutrophils. Cr-LAAO in its native form induced the neutrophil chemotaxis, suggesting that its primary structure is essential for stimulation the cell. p38 MAPK and PI3K have a role as signaling pathways of CR-LAAO induced chemotaxis. This toxin also induced the production of hydrogen peroxide and stimulated phagocytosis in neutrophils. Furthermore, Cr-LAAO was able to stimulate neutrophils to release IL-6, IL-8, MPO, LTB4 and PGE2. Together, the data showed that the Cr-LAAO triggers relevant proinflammatory events. PMID:27242041

  12. Sinking, merging and stationary plumes in a coupled chemotaxis-fluid model: a high-resolution numerical approach

    KAUST Repository

    Chertock, A.

    2012-02-02

    Aquatic bacteria like Bacillus subtilis are heavier than water yet they are able to swim up an oxygen gradient and concentrate in a layer below the water surface, which will undergo Rayleigh-Taylor-type instabilities for sufficiently high concentrations. In the literature, a simplified chemotaxis-fluid system has been proposed as a model for bio-convection in modestly diluted cell suspensions. It couples a convective chemotaxis system for the oxygen-consuming and oxytactic bacteria with the incompressible Navier-Stokes equations subject to a gravitational force proportional to the relative surplus of the cell density compared to the water density. In this paper, we derive a high-resolution vorticity-based hybrid finite-volume finite-difference scheme, which allows us to investigate the nonlinear dynamics of a two-dimensional chemotaxis-fluid system with boundary conditions matching an experiment of Hillesdon et al. (Bull. Math. Biol., vol. 57, 1995, pp. 299-344). We present selected numerical examples, which illustrate (i) the formation of sinking plumes, (ii) the possible merging of neighbouring plumes and (iii) the convergence towards numerically stable stationary plumes. The examples with stable stationary plumes show how the surface-directed oxytaxis continuously feeds cells into a high-concentration layer near the surface, from where the fluid flow (recurring upwards in the space between the plumes) transports the cells into the plumes, where then gravity makes the cells sink and constitutes the driving force in maintaining the fluid convection and, thus, in shaping the plumes into (numerically) stable stationary states. Our numerical method is fully capable of solving the coupled chemotaxis-fluid system and enabling a full exploration of its dynamics, which cannot be done in a linearised framework. © 2012 Cambridge University Press.

  13. Effect of SXWS/WSXWS peptides on chemotaxis and adhesion of the macrophage-like cell line J774.

    Science.gov (United States)

    Szabó, Rita; Láng, Orsolya; Láng, Júlia; Illyés, Eszter; Kőhidai, László; Hudecz, Ferenc

    2015-04-01

    WSXWS motif is a conserved amino acid sequence that is present in type I cytokine receptors. This motif that can be found both in the ligand binding chains and signal transducer molecule of the receptors with different amino acids at the position "X" plays a role in the receptor folding, ligand binding and signal transduction as well. Structural analysis proved that WSEWS motif of IL-6R is located in a highly accessible location in the protein. Structural properties and chemotaxis of a tetrapeptide library with SXWS sequence, where X was the 19 proteinogenic amino acids except cystein were systematically studied earlier. It has been proved that C-terminal amidation and the identity of amino acid X had a pronounced influence on the chemotactic properties but less of the structure of the peptides. Here, we present our findings on the effect of a tetrapeptide and a pentapeptide library with the sequence of SXWS and WSXWS on the chemotaxis and adhesion of J774 murine macrophage cell line. We studied the effect of the presence/absence of N-terminal tryptophan and the different amino acids at the X position on these physiological responses. Results indicated that amino acid X had a marked influence on chemotaxis, adhesion as well as on proliferation induced by (W)SXWS peptides. Elongation of SXWS sequence with a tryptophan at the N terminus also altered pronouncedly all the physiological responses of the cells studied. A good correlation could be observed between the chemotaxis and the proliferation and physicochemical parameters of the amino acid X. PMID:25683456

  14. N-WASP has the Ability to Compensate for the Loss of WASP in Macrophage Podosome Formation and Chemotaxis

    OpenAIRE

    Isaac, Beth M.; Ishihara, Dan; Nusblat, Leora M.; Gevrey, Jean-Claude; Dovas, Athanassios; Condeelis, John; Cox, Dianne

    2010-01-01

    Wiskott-Aldrich syndrome protein (WASP) and its homologue neural-WASP (N-WASP) are nucleation promoting factors that integrate receptor signaling with actin cytoskeleton rearrangement. While hematopoietic cells express both WASP and N-WASP, WASP deficiency results in altered cell morphology, loss of podosomes and defective chemotaxis. It was determined that cells from a mouse derived monocyte/macrophage cell line and primary cells of myeloid lineage expressed approximately 15-fold higher leve...

  15. Innate positive chemotaxis to pollen from crops and banker plants in predaceous biological control agents: towards new field lures?

    OpenAIRE

    Shu Li; Xiaoling Tan; Nicolas Desneux; Giovanni Benelli; Jing Zhao; Xinhai Li; Fan Zhang; Xiwu Gao; Su Wang

    2015-01-01

    Predator-prey interactions form the core of biological control of arthropod pests. Which tools can be used to monitor and collect carnivorous arthropods in natural habitats and targeted crops? Eco-friendly and effective field lures are urgently needed. In this research, we carried out olfactometer experiments assess innate positive chemotaxis to pollen of seven crop and banker plant by two important predatory biological control agents: the coccinellid Propylea japonica (Thunberg) and the anth...

  16. ELMO1 Directly Interacts with Gβγ Subunit to Transduce GPCR Signaling to Rac1 Activation in Chemotaxis

    Science.gov (United States)

    Wang, Youhong; Xu, Xuehua; Pan, Miao; Jin, Tian

    2016-01-01

    Diverse chemokines bind to G protein-coupled receptors (GPCRs) to activate the small GTPase Rac to regulate F-actin dynamics during chemotaxis. ELMO and Dock proteins form complexes that function as guanine nucleotide exchange factors (GEFs) for Rac activation. However, the linkage between GPCR activation and the ELMO/Dock-mediated Rac activation is not fully understood. In the present study, we show that chemoattractants induce dynamic membrane translocation of ELMO1 in mammalian cells. ELMO1 plays an important role in GPCR-mediated chemotaxis. We also reveal that ELMO1 and Dock1 form a stable complex. Importantly, activation of chemokine GPCR promotes the interaction between ELMO1 and Gβγ. The ELMO1-Gβγ interaction is through the N-terminus of ELMO1 protein and is important for the membrane translocation of ELMO1. ELMO1 is required for Rac1 activation upon chemoattractant stimulation. Our results suggest that chemokine GPCR-mediated interaction between Gβγ and ELMO1/Dock1 complex might serve as an evolutionarily conserved mechanism for Rac activation to regulate actin cytoskeleton for chemotaxis of human cells.

  17. Contribution of Individual Chemoreceptors to Sinorhizobium meliloti Chemotaxis Towards Amino Acids of Host and Nonhost Seed Exudates.

    Science.gov (United States)

    Webb, Benjamin A; Helm, Richard F; Scharf, Birgit E

    2016-03-01

    Plant seeds and roots exude a spectrum of molecules into the soil that attract bacteria to the spermosphere and rhizosphere, respectively. The alfalfa symbiont Sinorhizobium meliloti utilizes eight chemoreceptors (McpT to McpZ and IcpA) to mediate chemotaxis. Using a modified hydrogel capillary chemotaxis assay that allows data quantification and larger throughput screening, we defined the role of S. meliloti chemoreceptors in sensing its host, Medicago sativa, and a closely related nonhost, Medicago arabica. S. meliloti wild type and most single-deletion strains displayed comparable chemotaxis responses to host or nonhost seed exudate. However, while the mcpZ mutant responded like wild type to M. sativa exudate, its reaction to M. arabica exudate was reduced by 80%. Even though the amino acid (AA) amounts released by both plant species were similar, synthetic AA mixtures that matched exudate profiles contributed differentially to the S. meliloti wild-type response to M. sativa (23%) and M. arabica (37%) exudates, with McpU identified as the most important chemoreceptor for AA. Our results show that S. meliloti is equally attracted to host and nonhost legumes; however, AA play a greater role in attraction to M. arabica than to M. sativa, with McpZ being specifically important in sensing M. arabica. PMID:26713349

  18. Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement Component C5a.

    Science.gov (United States)

    Taylor, Lewis; Brodermann, Maximillian Hugo; McCaffary, David; Iqbal, Asif Jilani; Greaves, David R

    2016-01-01

    Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies. Treatment of RAW264.7 macrophages, BMDMs and human monocytes with netrin-1 inhibited their chemotaxis towards C5a, as measured using two different real-time methods. This inhibitory effect was found to be dependent on netrin-1 receptor signalling, as an UNC5b blocking antibody was able to reverse netrin-1 inhibition of C5a induced BMDM migration. Treatment of BMDMs with netrin-1 had no effect on C5aR1 proximal signalling events, as surface C5aR1 expression, internalisation and intracellular Ca2+ release following C5aR1 ligation remained unaffected after netrin-1 exposure. We next examined receptor distal events that occur following C5aR1 activation, but found that netrin-1 was unable to inhibit C5a induced phosphorylation of ERK1/2, Akt and p38, pathways important for cellular migration. Furthermore, netrin-1 treatment had no effect on BMDM cytoskeletal rearrangement following C5a stimulation as determined by microscopy and real-time electrical impedance sensing. Taken together these data highlight that netrin-1 inhibits monocyte and macrophage cell migration, but that the mechanism behind this effect remains unresolved. Nevertheless, netrin-1 and its cognate receptors warrant further investigation as they may represent a potential avenue for the development of

  19. Chemotaxis and Binding of Pseudomonas aeruginosa to Scratch-Wounded Human Cystic Fibrosis Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Christian Schwarzer

    Full Text Available Confocal imaging was used to characterize interactions of Pseudomonas aeruginosa (PA, expressing GFP or labeled with Syto 11 with CF airway epithelial cells (CFBE41o-, grown as confluent monolayers with unknown polarity on coverglasses in control conditions and following scratch wounding. Epithelia and PAO1-GFP or PAK-GFP (2 MOI were incubated with Ringer containing typical extracellular salts, pH and glucose and propidium iodide (PI, to identify dead cells. PAO1 and PAK swam randomly over and did not bind to nonwounded CFBE41o- cells. PA migrated rapidly (began within 20 sec, maximum by 5 mins and massively (10-80 fold increase, termed "swarming", but transiently (random swimming after 15 mins, to wounds, particularly near cells that took up PI. Some PA remained immobilized on cells near the wound. PA swam randomly over intact CFBE41o- monolayers and wounded monolayers that had been incubated with medium for 1 hr. Expression of CFTR and altered pH of the media did not affect PA interactions with CFBE41o- wounds. In contrast, PAO1 swarming and immobilization along wounds was abolished in PAO1 (PAO1ΔcheYZABW, no expression of chemotaxis regulatory components cheY, cheZ, cheA, cheB and cheW and greatly reduced in PAO1 that did not express amino acid receptors pctA, B and C (PAO1ΔpctABC and in PAO1 incubated in Ringer containing a high concentration of mixed amino acids. Non-piliated PAKΔpilA swarmed normally towards wounded areas but bound infrequently to CFBE41o- cells. In contrast, both swarming and binding of PA to CFBE41o- cells near wounds were prevented in non-flagellated PAKΔfliC. Data are consistent with the idea that (i PA use amino acid sensor-driven chemotaxis and flagella-driven swimming to swarm to CF airway epithelial cells near wounds and (ii PA use pili to bind to epithelial cells near wounds.

  20. Maneuverability and chemotaxis of Caenorhabditis elegans in three-dimensional environments

    Science.gov (United States)

    Blawzdziewicz, Jerzy; Bilbao, Alejandro; Patel, Amar; Vanapalli, Siva

    2015-11-01

    Locomotion of the nematode C. elegans in water and complex fluids has recently been investigated to gain insight into neuromuscular control of locomotion and to shed light on nematode evolutionary adaptation to environments with varying mechanical properties. Previous studies focused mainly on locomotion efficiency and on adaptation of the nematode gait to the surrounding medium. Much less attention has been devoted to nematode maneuverability, in spite of its crucial role in the survival of the animal. Recently we have provided a quantitative analysis of turning maneuvers of crawling and swimming nematodes on flat surfaces and in 2D fluid layers. Based on this work, we follow with the first full 3D description of how C. elegans moves in complex 3D environments. We show that by superposing body twist and 2D undulations, a burrowing or swimming nematode can rotate the undulation plane and change the direction of motion within that plane by varying undulation-wave parameters. A combination of these corkscrew maneuvers and 2D turns allows the nematode to explore 3D space. We conclude by analyzing 3D chemotaxis of nematodes burrowing in gel and swimming in water, which demonstrates an important application of our maneuverability model. This work was supported by NSF grant CBET-1059745.

  1. Auto-aggregation in zoospores of Phytophthora infestans: the cooperative roles of bioconvection and chemotaxis.

    Science.gov (United States)

    Savory, Andrew I M; Grenville-Briggs, Laura J; Wawra, Stephan; van West, Pieter; Davidson, Fordyce A

    2014-05-01

    Phytophthora infestans is a highly destructive plant pathogen. It was the cause of the infamous Irish potato famine in the nineteenth century and remains to this day a significant global problem with associated costs estimated at $3 billion annually. Key to the success of this pathogen is the dispersal of free-swimming cells called zoospores. A poorly understood aspect of zoospore behaviour is auto-aggregation--the spontaneous formation of large-scale patterns in cell density. Current competing hypotheses suggest that these patterns are formed by one of two distinct mechanisms: chemotaxis and bioconvection. In this paper, we present mathematical and experimental results that together provide strong evidence that auto-aggregation can only result from a combination of these mechanisms, each having a distinct, time-separated role. A better understanding of the underlying infection mechanisms of P. infestans and potentially other Phytophthora species will in the longer term lead to advances in preventative treatment and thus potentially significant savings in socio-economic costs. PMID:24598206

  2. SLAMF1 regulation of chemotaxis and autophagy determines CLL patient response

    Science.gov (United States)

    Bologna, Cinzia; Buonincontri, Roberta; Serra, Sara; Vaisitti, Tiziana; Audrito, Valentina; Brusa, Davide; Pagnani, Andrea; Coscia, Marta; D’Arena, Giovanni; Mereu, Elisabetta; Piva, Roberto; Furman, Richard R.; Rossi, Davide; Gaidano, Gianluca; Terhorst, Cox; Deaglio, Silvia

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is a variable disease; therefore, markers to identify aggressive forms are essential for patient management. Here, we have shown that expression of the costimulatory molecule and microbial sensor SLAMF1 (also known as CD150) is lost in a subset of patients with an aggressive CLL that associates with a shorter time to first treatment and reduced overall survival. SLAMF1 silencing in CLL-like Mec-1 cells, which constitutively express SLAMF1, modulated pathways related to cell migration, cytoskeletal organization, and intracellular vesicle formation and recirculation. SLAMF1 deficiency associated with increased expression of CXCR4, CD38, and CD44, thereby positively affecting chemotactic responses to CXCL12. SLAMF1 ligation with an agonistic monoclonal antibody increased ROS accumulation and induced phosphorylation of p38, JNK1/2, and BCL2, thereby promoting the autophagic flux. Beclin1 dissociated from BCL2 in response to SLAMF1 ligation, resulting in formation of the autophagy macrocomplex, which contains SLAMF1, beclin1, and the enzyme VPS34. Accordingly, SLAMF1-silenced cells or SLAMF1lo primary CLL cells were resistant to autophagy-activating therapeutic agents, such as fludarabine and the BCL2 homology domain 3 mimetic ABT-737. Together, these results indicate that loss of SLAMF1 expression in CLL modulates genetic pathways that regulate chemotaxis and autophagy and that potentially affect drug responses, and suggest that these effects underlie unfavorable clinical outcome experienced by SLAMF1lo patients. PMID:26619119

  3. A Circuit for Gradient Climbing in C. elegans Chemotaxis

    Directory of Open Access Journals (Sweden)

    Johannes Larsch

    2015-09-01

    Full Text Available Animals have a remarkable ability to track dynamic sensory information. For example, the nematode Caenorhabditis elegans can locate a diacetyl odor source across a 100,000-fold concentration range. Here, we relate neuronal properties, circuit implementation, and behavioral strategies underlying this robust navigation. Diacetyl responses in AWA olfactory neurons are concentration and history dependent; AWA integrates over time at low odor concentrations, but as concentrations rise, it desensitizes rapidly through a process requiring cilia transport. After desensitization, AWA retains sensitivity to small odor increases. The downstream AIA interneuron amplifies weak odor inputs and desensitizes further, resulting in a stereotyped response to odor increases over three orders of magnitude. The AWA-AIA circuit drives asymmetric behavioral responses to odor increases that facilitate gradient climbing. The adaptation-based circuit motif embodied by AWA and AIA shares computational properties with bacterial chemotaxis and the vertebrate retina, each providing a solution for maintaining sensitivity across a dynamic range.

  4. The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis

    Directory of Open Access Journals (Sweden)

    Constant Stephanie

    2011-10-01

    Full Text Available Abstract Background Previous studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp. However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression. Results Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA. Conclusions Our results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.

  5. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

    Science.gov (United States)

    Bhuiyan, Md Saruar; Ellett, Felix; Murray, Gerald L; Kostoulias, Xenia; Cerqueira, Gustavo M; Schulze, Keith E; Mahamad Maifiah, Mohd Hafidz; Li, Jian; Creek, Darren J; Lieschke, Graham J; Peleg, Anton Y

    2016-08-23

    Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease. PMID:27506797

  6. Local Generation of Kynurenines Mediates Inhibition of Neutrophil Chemotaxis by Uropathogenic Escherichia coli.

    Science.gov (United States)

    Loughman, Jennifer A; Yarbrough, Melanie L; Tiemann, Kristin M; Hunstad, David A

    2016-04-01

    During epithelial infections, pathogenic bacteria employ an array of strategies to attenuate and evade host immune responses, including the influx of polymorphonuclear leukocytes (PMN; neutrophils). Among the most common bacterial infections in humans are those of the urinary tract, caused chiefly by uropathogenicEscherichia coli(UPEC). During the establishment of bacterial cystitis, UPEC suppresses innate responses via multiple independent strategies. We recently described UPEC attenuation of PMN trafficking to the urinary bladder through pathogen-specific local induction of indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme previously shown to have regulatory activity only in adaptive immunity. Here, we investigated the mechanism by which IDO induction attenuates PMN migration. Local tryptophan limitation, by which IDO is known to influence T cell longevity and proliferation, was not involved in its effect on PMN trafficking. Instead, metabolites in the IDO pathway, particularlyl-kynurenine, directly suppressed PMN transepithelial migration and induced an attached, spread morphology in PMN both at rest and in the presence of chemotactic stimuli. Finally, kynurenines represent known ligands of the mammalian aryl hydrocarbon receptor (AHR), and UPEC infection ofAhr(-/-)mice recapitulated the derepressed PMN recruitment observed previously inIdo1(-/-)mice. UPEC therefore suppresses neutrophil migration early in bacterial cystitis by eliciting an IDO-mediated increase in local production of kynurenines, which act through the AHR to impair neutrophil chemotaxis. PMID:26857571

  7. Boundedness and decay enforced by quadratic degradation in a three-dimensional chemotaxis-fluid system

    Science.gov (United States)

    Tao, Youshan; Winkler, Michael

    2015-10-01

    The coupled chemotaxis-fluid system &n_t + u\\cdot nabla n = Δ n - nabla \\cdot (n nabla c) +rn-μ n^2, & c_t + u\\cdot nabla c = Δ c-c+n , & u_t + nabla P = Δ u + n nabla φ + g(x,t), & nabla \\cdot u = 0, is considered under no-flux boundary conditions for n and c and no-slip boundary conditions for u in three-dimensional bounded domains with smooth boundary, where {r≥ 0} and {μ > 0} are given constants and {φin W^{1, ∞}(Ω)} and {gin C^1(barΩ× [0, ∞)) \\cap L^∞(Ω× (0,∞))} are prescribed parameter functions. It is shown that under the explicit condition {μ≥ 23} and suitable regularity assumptions on the initial data, the corresponding initial-boundary problem possesses a global classical solution which is bounded. Apart from this, it is proved that if r = 0, then both n(·, t) and c(·, t) decay to zero with respect to the norm in {L^∞(Ω)} as {tto ∞}, and that if, moreover, {int_0^∞ int_Ω |g|^2 < ∞}, then also u(·, t)→ 0 in {L^∞(Ω)} as {tto ∞}.

  8. Polarization of cells and soft objects driven by mechanical interactions: Consequences for migration and chemotaxis

    Science.gov (United States)

    Leoni, M.; Sens, P.

    2015-02-01

    We study a generic model for the polarization and motility of self-propelled soft objects, biological cells, or biomimetic systems, interacting with a viscous substrate. The active forces generated by the cell on the substrate are modeled by means of oscillating force multipoles at the cell-substrate interface. Symmetry breaking and cell polarization for a range of cell sizes naturally "emerge" from long range mechanical interactions between oscillating units, mediated both by the intracellular medium and the substrate. However, the harnessing of cell polarization for motility requires substrate-mediated interactions. Motility can be optimized by adapting the oscillation frequency to the relaxation time of the system or when the substrate and cell viscosities match. Cellular noise can destroy mechanical coordination between force-generating elements within the cell, resulting in sudden changes of polarization. The persistence of the cell's motion is found to depend on the cell size and the substrate viscosity. Within such a model, chemotactic guidance of cell motion is obtained by directionally modulating the persistence of motion, rather than by modulating the instantaneous cell velocity, in a way that resembles the run and tumble chemotaxis of bacteria.

  9. Quantification of chemotaxis during pediatric cardiac surgery by flow and laser scanning cytometry

    Science.gov (United States)

    Tarnok, Attila; Schmid, Joerg W.; Osmancik, Pavel; Lenz, Dominik; Pipek, Michal; Hambsch, Joerg; Gerstner, Andreas O.; Schneider, Peter

    2002-05-01

    Cardiac surgery with cardiopulmonary bypass (CPB) alters the leukocyte composition of the peripheral blood (PB). This response contributes to the sometimes adverse outcome with capillary leakage. Migration of activated cells to sites of inflammation, driven by chemokines is part of this response. In order to determine the chemotactic activity of patients serum during and after surgery we established an assay for PB leukocytes (PBL). PBL from healthy donors were isolated and 250,000 cells were placed into a migration chamber separated by a filter from a second lower chamber filled with patient serum. After incubation cells from top and bottom chamber were removed and stained with a cocktail of monoclonal antibodies for leukocyte subsets and analyzed on a flow cytometer (FCM). Cells at the bottom of the filter belong to the migrating compartment and were quantified by LSC after staining of nucleated cells. Increased chemotactic activity started at onset of anaesthesia followed by a phase of low activity immediately after surgery and a second phase of a high post-operative activity. The in vitro results correlated with results obtained by immunopenotyping of circulating PBL. Manipulation of the chemokine pattern might prove beneficial to prevent extravasation of cells leading to tissue damage. In chemotaxis assays with low amount of available serum the combined use of FCM and Laser Scanning LSC proved as an appropriate analytical tool.

  10. Fractional Adams-Bashforth/Moulton methods: An application to the fractional Keller-Segel chemotaxis system

    Science.gov (United States)

    Zayernouri, Mohsen; Matzavinos, Anastasios

    2016-07-01

    We first formulate a fractional class of explicit Adams-Bashforth (A-B) and implicit Adams-Moulton (A-M) methods of first- and second-order accuracy for the time-integration of t τ 0 CD u (x,t) = g (t ; u), τ ∈ (0 , 1 ], where t τ 0 CD denotes the fractional derivative in the Caputo sense. In this fractional setting and in contrast to the standard Adams methods, an extra history load term emerges and the associated weight coefficients are τ-dependent. However when τ = 1, the developed schemes reduce to the well-known A-B and A-M methods with standard coefficients. Hence, in terms of scientific computing, our approach constitutes a minimal modification of the existing Adams libraries. Next, we develop an implicit-explicit (IMEX) splitting scheme for linear and nonlinear fractional PDEs of a general advection-reaction-diffusion type, and we apply our scheme to the time-space fractional Keller-Segel chemotaxis system. In this context, we evaluate the nonlinear advection term explicitly, employing the fractional A-B method in the prediction step, and we treat the corresponding diffusion term implicitly in the correction step using the fractional A-M scheme. Moreover, we perform the corresponding spatial discretization by employing an efficient and spectrally-accurate fractional spectral collocation method. Our numerical experiments exhibit the efficiency of the proposed IMEX scheme in solving nonlinear fractional PDEs.

  11. ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML.

    Science.gov (United States)

    Capala, Marta E; Vellenga, Edo; Schuringa, Jan Jacob

    2014-01-01

    Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML) cells (n = 46), their more differentiated CD34- leukemic progeny, and normal CD34+ bone marrow cells (n = 31) and focused on differentially expressed genes involved in adhesion and migration. Thus, Engulfment and Motility protein 1 (ELMO1) was identified amongst the top 50 most differentially expressed genes. ELMO1 is a crucial link in the signaling cascade that leads to activation of RAC GTPases and cytoskeleton rearrangements. We confirmed increased ELMO1 expression at the mRNA and protein level in a panel of AML samples and showed that high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK) AML in three large independent patient cohorts. Downmodulation of ELMO1 in human CB CD34+ cells did not significantly alter expansion, progenitor frequency or differentiation in stromal co-cultures, but did result in a decreased frequency of stem cells in LTC-IC assays. In BCR-ABL-transduced human CB CD34+ cells depletion of ELMO1 resulted in a mild decrease in proliferation, but replating capacity of progenitors was severely impaired. Downregulation of ELMO1 in a panel of primary CD34+ AML cells also resulted in reduced long-term growth in stromal co-cultures in two out of three cases. Pharmacological inhibition of the ELMO1 downstream target RAC resulted in a severely impaired proliferation and survival of leukemic cells. Finally, ELMO1 depletion caused a marked decrease in SDF1-induced chemotaxis of leukemic cells. Taken together, these data show that inhibiting the ELMO1-RAC axis might be an alternative way to target leukemic cells. PMID:25360637

  12. Boundedness in a quasilinear chemotaxis-haptotaxis system with logistic source

    Science.gov (United States)

    Liu, Ji; Zheng, Jiashan; Wang, Yifu

    2016-04-01

    In this paper, we consider the quasilinear chemotaxis-haptotaxis system u_t=nabla\\cdot(D(u)nabla u)-nabla\\cdot(S_1(u)nabla v)-nabla\\cdot(S_2(u)nabla w)+uf(u,w),quad xinΩ, t > 0,v_t=Δ v-v+u,quad xinΩ, t > 0,w_t=-vw,quad xinΩ, t > 0 in a bounded smooth domain {Ωsubset R^n (n≥1)} under zero-flux boundary conditions, where the nonlinearities {D, S_1} and {S_2} are assumed to generalize the prototypes D(u)=CD(u+1)^{m-1}, S_1(u)=C_{S_1}u(u+1)^{q_1-1} quad {and} quad S_2(u)=C_{S_2}u(u+1)^{q_2-1} with {C_D,C_{S_1},C_{S_2} > 0, m,q_1,q_2in R} and {f(u,w)in C^1([0,+infty)×[0,+∞))} fulfills f(u,w)≤ r-buquad {for all} ~u≥ 0quad {and} quad w≥ 0, where {r > 0, b > 0.} Assuming nonnegative initial data {u_0(x)in W^{1,∞}(Ω),v_0(x)in W^{1,∞}(Ω)} and {w_0(x)in C^{2,α}(barΩ)} for some {αin(0,1),} we prove that (i) for {n≤2,} if q_1,q_2\\ 2,} if {max{q_1,q_2} 2-2/n} or {max{q_1,q_2} < m+2/n-1} and {m≤ 1,} then {(star)} has a unique nonnegative classical solution which is globally bounded.

  13. Multiple Regulatory Roles of the Mouse Transmembrane Adaptor Protein NTAL in Gene Transcription and Mast Cell Physiology

    Czech Academy of Sciences Publication Activity Database

    Polakovičová, Iva; Dráberová, Lubica; Šimíček, Michal; Dráber, Petr

    2014-01-01

    Roč. 9, č. 8 (2014), e105539. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GBP302/12/G101; GA MŠk LD12073 Institutional support: RVO:68378050 Keywords : mast cells * NTAL * microarray gene-expression profiling * spreading * chemotaxis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  14. Chelation of Free Zn(2+) Impairs Chemotaxis, Phagocytosis, Oxidative Burst, Degranulation, and Cytokine Production by Neutrophil Granulocytes.

    Science.gov (United States)

    Hasan, Rafah; Rink, Lothar; Haase, Hajo

    2016-05-01

    Neutrophil granulocytes are the largest leukocyte population in the blood and major players in the innate immune response. Impaired neutrophil function has been reported in in vivo studies with zinc-deficient human subjects and experimental animals. Moreover, in vitro formation of neutrophil extracellular traps has been shown to depend on free intracellular Zn(2+). This study investigates the requirement of Zn(2+) for several other essential neutrophil functions, such as chemotaxis, phagocytosis, cytokine production, and degranulation. To exclude artifacts resulting from indirect effects of zinc deprivation, such as impaired hematopoietic development and influences of other immune cells, direct effects of zinc deprivation were tested in vitro using cells isolated from healthy human donors. Chelation of Zn(2+) by the membrane permeable chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) reduced granulocyte migration toward N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF) and IL-8, indicating a role of free intracellular Zn(2+) in chemotaxis. However, a direct action of Zn(2+) as a chemoattractant, as previously reported by others, was not observed. Similar to chemotaxis, phagocytosis, oxidative burst, and granule release were also impaired in TPEN-treated granulocytes. Moreover, Zn(2+) contributes to the regulatory role of neutrophil granulocytes in the inflammatory response by affecting the cytokine production by these cells. TPEN inhibited the lipopolysaccharide-induced secretion of chemotactic IL-8 and also anti-inflammatory IL-1ra. In conclusion, free intracellular Zn(2+) plays essential roles in multiple neutrophil functions, affecting extravasation to the site of the infection, uptake and killing of microorganisms, and inflammation. PMID:26400651

  15. Boundedness and global existence in the higher-dimensional parabolic-parabolic chemotaxis system with/without growth source

    Science.gov (United States)

    Xiang, Tian

    2015-06-01

    In this paper, we are concerned with a general class of quasilinear parabolic-parabolic chemotaxis systems with/without growth source, under homogeneous Neumann boundary conditions in a smooth bounded domain Ω ⊂Rn with n ≥ 2. It is recently known that blowup is possible even in the presence of superlinear growth restrictions. Here, we derive new and interesting characterizations on the growth versus the boundedness. We show that the hard task of proving the L∞-boundedness of the cell density can be reduced to proving its Lr-boundedness. In other words, we show that the Lr-boundedness of the cell density can successfully guarantee its L∞-boundedness and hence its global boundedness, where r = n + ɛ or n/2 + ɛ depending on whether the growth restriction is essentially linear (including no growth) or superlinear. Hence, a blowup solution also blows up in Lp-norm for any suitably large p. More detailed information on how the growth source affects the boundedness of the solution is derived. These results reveal deep understandings of blowup mechanism for chemotaxis models. Then we use these criteria to establish uniform boundedness and hence global existence of the underlying models: logistic source in 2-D, cubic source as initially proposed by Mimura and Tsujikawa in 3-D, [ (n - 1) + ɛ ]st source in n-D with n ≥ 4. As a consequence, in a chemotaxis-growth model, blowup is impossible if the growth effect is suitably strong. Finally, we underline that our results remove the commonly assumed convexity on the domain Ω.

  16. Chemotaxis of Ralstonia eutropha JMP134(pJP4) to the Herbicide 2,4-Dichlorophenoxyacetate

    OpenAIRE

    Hawkins, Andrew C.; Harwood, Caroline S.

    2002-01-01

    Ralstonia eutropha JMP134(pJP4) and several other species of motile bacteria can degrade the herbicide 2,4-dichlorophenoxyacetate (2,4-D), but it was not known if bacteria could sense and swim towards 2,4-D by the process of chemotaxis. Wild-type R. eutropha cells were chemotactically attracted to 2,4-D in swarm plate assays and qualitative capillary assays. The chemotactic response was induced by growth with 2,4-D and depended on the presence of the catabolic plasmid pJP4, which harbors the ...

  17. Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

    International Nuclear Information System (INIS)

    Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine (3H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

  18. Mutation of a Src phosphorylation site in the PDGF beta-receptor leads to increased PDGF-stimulated chemotaxis but decreased mitogenesis

    DEFF Research Database (Denmark)

    Hansen, Klaus; Johnell, M; Siegbahn, A; Rorsman, C; Engström, U; Wernstedt, C; Heldin, C H; Rönnstrand, L

    1996-01-01

    phosphorylated by Src. Cell lines expressing a beta-receptor mutant, in which Tyr934 was replaced with a phenyalanine residue, showed reduced mitogenic signaling in response to PDGF-BB. In contrast, the mutant receptor mediated increased signals for chemotaxis and actin reorganization. Whereas the motility...... responses of cells expressing wild-type beta-receptors were attenuated by inhibition of phosphatidylinositol 3'-kinase, those of cells expressing the mutant receptor were only slightly influenced. In contrast, PDGF-BB-induced chemotaxis of the cells with the mutant receptor was attenuated by inhibition of...... protein kinase C, whereas the chemotaxis of cells expressing the wild-type beta-receptor was less affected. Moreover, the PDGF-BB-stimulated tyrosine phosphorylation of phospholipase C-gamma was increased in the mutant receptor cells compared with wild-type receptor cells. In conclusion, the...

  19. Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

    Science.gov (United States)

    Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

    2016-01-01

    Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID:27367541

  20. Neutrophils lacking platelet-endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2-mediated chemotaxis.

    Science.gov (United States)

    Wu, Yue; Stabach, Paul; Michaud, Michael; Madri, Joseph A

    2005-09-15

    Time-lapsed videomicroscopy was used to study the migration of platelet-endothelial cell adhesion molecule-1-deficient (PECAM-1(-/-)) murine neutrophils undergoing chemotaxis in Zigmond chambers containing IL-8, KC, or fMLP gradients. PECAM-1(-/-) neutrophils failed to translocate up the IL-8, KC, and fMLP gradients. Significant reductions in cell motility and cell spreading were also observed in IL-8 or KC gradients. In wild-type neutrophils, PECAM-1 and F-actin were colocalized at the leading fronts of polarized cells toward the gradient. In contrast, in PECAM-1(-/-) neutrophils, although F-actin also localized to the leading front of migrating cells, F-actin polymerization was unstable, and cycling was remarkably increased compared with that of wild-type neutrophils. This may be due to the decreased cytokine-induced mobilization of the actin-binding protein, moesin, into the cytoskeleton of PECAM-1(-/-) neutrophils. PECAM-1(-/-) neutrophils also exhibited intracellularly dislocalized Src homology 2 domain containing phosphatase 1 (SHP-1) and had less IL-8-induced SHP-1 phosphatase activity. These results suggest that PECAM-1 regulates neutrophil chemotaxis by modulating cell motility and directionality, in part through its effects on SHP-1 localization and activation. PMID:16148090

  1. CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.

    Science.gov (United States)

    Anderson, Albert M; Fennema-Notestine, Christine; Umlauf, Anya; Taylor, Michael J; Clifford, David B; Marra, Christina M; Collier, Ann C; Gelman, Benjamin B; McArthur, Justin C; McCutchan, J Allen; Simpson, David M; Morgello, Susan; Grant, Igor; Letendre, Scott L

    2015-10-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R (2) 0.179, p FGM (R (2) 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals. PMID:26069183

  2. Cluster–cluster aggregation with particle replication and chemotaxy: a simple model for the growth of animal cells in culture

    International Nuclear Information System (INIS)

    Aggregation of animal cells in culture comprises a series of motility, collision and adhesion processes of basic relevance for tissue engineering, bioseparations, oncology research and in vitro drug testing. In the present paper, a cluster–cluster aggregation model with stochastic particle replication and chemotactically driven motility is investigated as a model for the growth of animal cells in culture. The focus is on the scaling laws governing the aggregation kinetics. Our simulations reveal that in the absence of chemotaxy the mean cluster size and the total number of clusters scale in time as stretched exponentials dependent on the particle replication rate. Also, the dynamical cluster size distribution functions are represented by a scaling relation in which the scaling function involves a stretched exponential of the time. The introduction of chemoattraction among the particles leads to distribution functions decaying as power laws with exponents that decrease in time. The fractal dimensions and size distributions of the simulated clusters are qualitatively discussed in terms of those determined experimentally for several normal and tumoral cell lines growing in culture. It is shown that particle replication and chemotaxy account for the simplest cluster size distributions of cellular aggregates observed in culture

  3. In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor

    Directory of Open Access Journals (Sweden)

    Anne Silvestre

    2015-07-01

    Full Text Available Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction. The tissue inflammation associated with tumour necrosis factor (TNF secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1 stained the E. histolytica trophozoite surface and (on immunoblots binds to a 150-kDa protein. Proteome screening with the TNFR1 sequence revealed a BspA family protein in E. histolytica that carries a TNFR signature domain and six leucine-rich repeats (named here as "cell surface protein", CSP, in view of its cellular location. Cell surface protein shares structural homologies with Toll-Like receptors, colocalizes with TNF and is internalized in TNF-containing vesicles. Reduction of cellular CSP levels abolished chemotaxis toward TNF and blocked parasite invasion of human colon. Conclusions: there is a clear link between TNF chemotaxis, CSP and pathogenesis.

  4. Selective induction of gene expression and second-messenger accumulation in Dictyostelium discoideum by the partial chemotactic antagonist 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate

    NARCIS (Netherlands)

    Peters, Dorien J.M.; Bominaar, Anthony A.; Snaar-Jagalska, B. Ewa; Brandt, Raymond; Haastert, Peter J.M. van; Ceccarelli, Adriano; Williams, Jeffrey G.; Schaap, Pauline

    1991-01-01

    During development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We describe a cAMP derivative, 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate (8-CPT-cAMP), whic

  5. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Cammer, Michael; Lehman, Jonathan;

    2010-01-01

    . Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA is...

  6. A model invalidation-based approach for elucidating biological signalling pathways, applied to the chemotaxis pathway in R. sphaeroides

    Directory of Open Access Journals (Sweden)

    Hamadeh Abdullah

    2009-10-01

    Full Text Available Abstract Background Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models. Results In this paper, we developed a novel mathematical model/experiment design cycle to help determine the probable network connectivity by iteratively invalidating models corresponding to competing signalling pathways. To do this, we systematically design experiments in silico that discriminate best between models of the competing signalling pathways. The method determines the inputs and parameter perturbations that will differentiate best between model outputs, corresponding to what can be measured/observed experimentally. We applied our method to the unknown connectivities in the chemotaxis pathway of the bacterium Rhodobacter sphaeroides. We first developed several models of R. sphaeroides chemotaxis corresponding to different signalling networks, all of which are biologically plausible. Parameters in these models were fitted so that they all represented wild type data equally well. The models were then compared to current mutant data and some were invalidated. To discriminate between the remaining models we used ideas from control systems theory to determine efficiently in silico an input profile that would result in the biggest difference in model outputs. However, when we applied this input to the models, we found it to be insufficient for discrimination in silico. Thus, to achieve better discrimination, we determined the best change in initial conditions (total protein concentrations as well as the best change in the input profile. The designed experiments were then performed on live cells and the resulting

  7. Microfluidic assay for precise measurements of mouse, rat, and human neutrophil chemotaxis in whole-blood droplets.

    Science.gov (United States)

    Jones, Caroline N; Hoang, Anh N; Martel, Joseph M; Dimisko, Laurie; Mikkola, Amy; Inoue, Yoshitaka; Kuriyama, Naohide; Yamada, Marina; Hamza, Bashar; Kaneki, Masao; Warren, H Shaw; Brown, Diane E; Irimia, Daniel

    2016-07-01

    Animal models of human disease differ in innate immune responses to stress, pathogens, or injury. Precise neutrophil phenotype measurements could facilitate interspecies comparisons. However, such phenotype comparisons could not be performed accurately with the use of current assays, as they require the separation of neutrophils from blood using species-specific protocols, and they introduce distinct artifacts. Here, we report a microfluidic technology that enables robust characterization of neutrophil migratory phenotypes in a manner independent of the donor species and performed directly in a droplet of whole blood. The assay relies on the particular ability of neutrophils to deform actively during chemotaxis through microscale channels that block the advance of other blood cells. Neutrophil migration is measured directly in blood, in the presence of other blood cells and serum factors. Our measurements reveal important differences among migration counts, velocity, and directionality among neutrophils from 2 common mouse strains, rats, and humans. PMID:26819316

  8. Global existence and boundedness of radial solutions to a two dimensional fully parabolic chemotaxis system with general sensitivity

    Science.gov (United States)

    Fujie, Kentarou; Senba, Takasi

    2016-08-01

    This paper deals with positive radially symmetric solutions of the Neumann boundary value problem for the fully parabolic chemotaxis system, {ut=Δu‑∇ṡ(u∇χ(v))in Ω×(0,∞),τvt=Δv‑v+uin Ω×(0,∞), in a ball Ω \\subset {{{R}}2} with general sensitivity function χ (v) satisfying {χ\\prime}>0 and decaying property {χ\\prime}(s)\\to 0 (s\\to ∞ ), parameter τ \\in ≤ft(0,1\\right] and nonnegative radially symmetric initial data. It is shown that if τ \\in ≤ft(0,1\\right] is sufficiently small, then the problem has a unique classical radially symmetric solution, which exists globally and remains uniformly bounded in time. Especially, this result establishes global existence of solutions in the case χ (v)={χ0}log v for all {χ0}>0 , which has been left as an open problem.

  9. Relationship between chemical composition and biological function of Pseudomonas aeruginosa lipopolysaccharide: effect on human neutrophil chemotaxis and oxidative burst

    DEFF Research Database (Denmark)

    Kharazmi, A; Fomsgaard, A; Conrad, R S;

    1991-01-01

    There are conflicting data on the effect of bacterial lipopolysaccharides (LPS) on the function of human neutrophils. The present study was designed to examine the relationship between chemical composition and the modulatory effect of LPS on human neutrophil function. LPS was extracted from five...... strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients by the hot phenol-water method. Chemical characterization included neutral sugars, amino components, and fatty acids. Neutrophils isolated from peripheral blood of healthy individuals were preincubated with different concentrations...... neutrophil function seen as inhibition of neutrophil chemotaxis toward the chemotactic peptide f-Met-Leu-Phe and zymosan-activated serum (ZAS) and priming of the cells for less than or equal to 8-fold enhancement of chemiluminescence response to f-Met-Leu-Phe. Conversely, LPS from strain 1118-O:3 had no...

  10. 4D Tumorigenesis Model for Quantitating Coalescence, Directed Cell Motility and Chemotaxis, Identifying Unique Cell Behaviors, and Testing Anticancer Drugs.

    Science.gov (United States)

    Kuhl, Spencer; Voss, Edward; Scherer, Amanda; Lusche, Daniel F; Wessels, Deborah; Soll, David R

    2016-01-01

    A 4D high-resolution computer-assisted reconstruction and motion analysis system has been developed and applied to the long-term (14-30 days) analysis of cancer cells migrating and aggregating within a 3D matrix. 4D tumorigenesis models more closely approximate the tumor microenvironment than 2D substrates and, therefore, are improved tools for elucidating the interactions within the tumor microenvironment that promote growth and metastasis. The model we describe here can be used to analyze the growth of tumor cells, aggregate coalescence, directed cell motility and chemotaxis, matrix degradation, the effects of anticancer drugs, and the behavior of immune and endothelial cells mixed with cancer cells. The information given in this chapter is also intended to acquaint the reader with computer-assisted methods and algorithms that can be used for high-resolution 3D reconstruction and quantitative motion analysis. PMID:27271907

  11. Twitching motility and cAMP levels: signal transduction through a single methyl-accepting chemotaxis protein.

    Science.gov (United States)

    Jansari, Vibhuti H; Potharla, Vishwakanth Y; Riddell, Geoff T; Bardy, Sonia L

    2016-06-01

    The Pseudomonas aeruginosa Chp chemosensory system regulates twitching motility, intracellular adenosine 3('') 5(')-cyclic monophosphate (cAMP) levels and is postulated to be involved in directional twitching towards phosphatidylethanolamine (PE). Because PilJ is the only methyl-accepting chemotaxis protein (MCP) identified in the Chp system, we determined the role of PilJ in mediating signal transduction for the distinct outputs of this system. Mutants that lack the periplasmic domain of PilJ (pilJΔ74-273) showed lower levels of cAMP but retained directional twitching towards PE. While initial studies revealed reduced twitching motility by PilJΔ74-273, this was due to decreased cAMP levels. Our data illustrate the importance of the periplasmic domain of PilJ in regulating cAMP. This is the first time a defined domain within PilJ has been identified as having a distinct role in signal transduction. PMID:27190147

  12. Induction of macrophage chemotaxis by aortic extracts from patients with Marfan syndrome is related to elastin binding protein.

    Directory of Open Access Journals (Sweden)

    Gao Guo

    Full Text Available Marfan syndrome is an autosomal dominantly inherited disorder of connective tissue with prominent skeletal, ocular, and cardiovascular manifestations. Aortic aneurysm and dissection are the major determinants of premature death in untreated patients. In previous work, we showed that extracts of aortic tissues from the mgR mouse model of Marfan syndrome showed increased chemotactic stimulatory activity related to the elastin-binding protein. Aortic samples were collected from 6 patients with Marfan syndrome and 8 with isolated aneurysms of the ascending aorta. Control samples were obtained from 11 organ donors without known vascular or connective tissue diseases. Soluble proteins extracted from the aortic samples of the two patient groups were compared against buffer controls and against the aortic samples from controls with respect to the ability to induce macrophage chemotaxis as measured using a modified Boyden chamber, as well as the reactivity to a monoclonal antibody BA4 against bioactive elastin peptides using ELISA. Samples from Marfan patients displayed a statistically significant increase in chemotactic inductive activity compared to control samples. Additionally, reactivity to BA4 was significantly increased. Similar statistically significant increases were identified for the samples from patients with idiopathic thoracic aortic aneurysm. There was a significant correlation between the chemotactic index and BA4 reactivity, and the increases in chemotactic activity of extracts from Marfan patients could be inhibited by pretreatment with lactose, VGVAPG peptides, or BA4, which indicates the involvement of EBP in mediating the effects. Our results demonstrate that aortic extracts of patients with Marfan syndrome can elicit macrophage chemotaxis, similar to our previous study on aortic extracts of the mgR mouse model of Marfan syndrome (Guo et al., Circulation 2006; 114:1855-62.

  13. Leishmania amazonensis chemotaxis under glucose gradient studied by the strength and directionality of forces measured with optical tweezers

    Science.gov (United States)

    de Ysasa Pozzo, Liliana; Fontes, Adriana; de Thomaz, André A.; Barbosa, Luiz Carlos; Ayres, Diana Copi; Giorgio, Selma; Cesar, Carlos Lenz

    2007-02-01

    Chemotaxis is the mechanism microorganisms use to sense the environment surrounding them and to direct their movement towards attractive, or away from the repellent, chemicals. The biochemical sensing is almost the only way for communication between unicellular organisms. Prokaryote and Eukaryote chemotaxis has been mechanically studied mainly by observing the directionality and timing of the microorganisms movements subjected to a chemical gradient, but not through the directionality and strength of the forces it generates. To observe the vector force of microorganisms under a chemical gradient we developed a system composed of two large chambers connected by a tiny duct capable to keep the chemical gradient constant for more than ten hours. We also used the displacements of a microsphere trapped in an Optical Tweezers as the force transducer to measure the direction and the strength of the propulsion forces of flagellum of the microorganism under several gradient conditions. A 9μm diameter microsphere particle was trapped with a Nd:YAG laser and its movement was measured through the light scattered focused on a quadrant detector. We observed the behavior of the protozoa Leishmania amazonensis (eukaryote) under several glucose gradients. This protozoa senses the gradient around it by swimming in circles for three to five times following by tumbling, and not by the typical straight swimming/tumbling of bacteria. Our results also suggest that force direction and strength are also used to control its movement, not only the timing of swimming/tumbling, because we observed a higher force strength clearly directed towards the glucose gradient.

  14. Interleukin-17 (IL-17) Expression Is Reduced during Acute Myocardial Infarction: Role on Chemokine Receptor Expression in Monocytes and Their in Vitro Chemotaxis towards Chemokines

    OpenAIRE

    Guro Valen; Maghazachi, Azzam A; Sand, Kristin L; Jarle Vaage; Anton Baysa; Maria Troitskaya

    2012-01-01

    The roles of immune cells and their soluble products during myocardial infarction (MI) are not completely understood. Here, we observed that the percentages of IL-17, but not IL-22, producing cells are reduced in mice splenocytes after developing MI. To correlate this finding with the functional activity of IL-17, we sought to determine its effect on monocytes. In particular, we presumed that this cytokine might affect the chemotaxis of monocytes important for cardiac inflammation and remodel...

  15. Analysis of periplasmic sensor domains from Anaeromyxobacter dehalogenans 2CP-C: Structure of one sensor domain from a histidine kinase and another from a chemotaxis protein

    OpenAIRE

    Pokkuluri, P. Raj; Dwulit-Smith, Jeff; Duke, Norma E; Wilton, Rosemarie; Mack, Jamey C; Bearden, Jessica; Rakowski, Ella; Babnigg, Gyorgy; Szurmant, Hendrik; Joachimiak, Andrzej; Schiffer, Marianne

    2013-01-01

    Anaeromyxobacter dehalogenans is a δ-proteobacterium found in diverse soils and sediments. It is of interest in bioremediation efforts due to its dechlorination and metal-reducing capabilities. To gain an understanding on A. dehalogenans' abilities to adapt to diverse environments we analyzed its signal transduction proteins. The A. dehalogenans genome codes for a large number of sensor histidine kinases (HK) and methyl-accepting chemotaxis proteins (MCP); among these 23 HK and 11 MCP protein...

  16. Chemotaxis in Densely Populated Tissue Determines Germinal Center Anatomy and Cell Motility: A New Paradigm for the Development of Complex Tissues

    OpenAIRE

    Hawkins, Jared B; Jones, Mark T.; Plassmann, Paul E.; Thorley-Lawson, David A.

    2011-01-01

    Germinal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly struct...

  17. Chemotaxis in densely populated tissue determines germinal center anatomy and cell motility: a new paradigm for the development of complex tissues.

    Directory of Open Access Journals (Sweden)

    Jared B Hawkins

    Full Text Available Germinal centers (GCs are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.

  18. Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis

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    Tahtouh Muriel

    2012-02-01

    Full Text Available Abstract Background In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR, which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand. Methods Recombinant HmC1q (rHmC1q was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques. Results rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia. Conclusions A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal

  19. 木葡糖酸醋杆菌趋化性的初步研究%Preliminary Study of Chemotaxis of Gluconacetobacter xylinum

    Institute of Scientific and Technical Information of China (English)

    李晶; 贾士儒; 杨洪江; 闫林; 朱会霞

    2012-01-01

    Capillary assay was used in this research to investigate the chemotaxis of G. Xylinum. The results showed that pH,chemotactic time,temperature,amino acids,carbon resources,acids and metal all ions had influence on chemotaxis of G. Xylinum and the optimal chemotaxis of G. Xylinum happened when pH was 5 .temperature was 25-30 'C and the duration was 60 minutes. Among 7 kinds of amino acids tested, Z.-leucine,Z,-alanine,Z,-glycine,Z,-methionine promoted the chemotaxis of G. Xylinum. Among 6 kinds of carbohydrates, glucose promoted the chemotaxis of G. Xylinum remarkably, whereas sucrose, lactose, maltose, galactose and glycerol inhibited chemotactic response. Among 4 kinds of acids, citric acid inhabited chemotactic response of G. Xylinum significantly. So did Sn2+, Mn2+, Pb2+, Cr2+, Co2+.%采用毛细管法研究了木葡糖酸醋杆菌(Gluconacetobacter xylinum)的趋化性反应,结果显示pH、趋化时间、温度、氨基酸、碳源、酸和重金属离子对木葡糖酸醋杆菌趋化性反应有影响.木葡糖酸醋杆菌在温度25~30℃,pH为5时趋化性反应最高;最佳趋化时间为60 min;在7种氨基酸中L-亮氨酸、L-丙氨酸、L-甘氨酸、L-甲硫氨酸对木葡糖酸醋杆菌的趋化性反应有促进作用;6种碳源中,葡萄糖对趋化性有促进作用,蔗糖、乳糖、麦芽糖、半乳糖、甘油对趋化性反应有抑制作用;4种酸中柠檬酸对趋化性反应有显著的抑制作用;Sn2+、Mn2+、pb2+、Cr2+、Co2+离子都对趋化性反应有抑制作用.

  20. HIV-1 Nef Binds the DOCK2-ELMO1 Complex to Activate Rac and Inhibit Lymphocyte Chemotaxis

    Directory of Open Access Journals (Sweden)

    Janardhan Ajit

    2004-01-01

    Full Text Available The infectious cycle of primate lentiviruses is intimately linked to interactions between cells of the immune system. Nef, a potent virulence factor, alters cellular environments to increase lentiviral replication in the host, yet the mechanisms underlying these effects have remained elusive. Since Nef likely functions as an adaptor protein, we exploited a proteomic approach to directly identify molecules that Nef targets to subvert the signaling machinery in T cells. We purified to near homogeneity a major Nef-associated protein complex from T cells and identified by mass spectroscopy its subunits as DOCK2-ELMO1, a key activator of Rac in antigen- and chemokine-initiated signaling pathways, and Rac. We show that Nef activates Rac in T cell lines and in primary T cells following infection with HIV-1 in the absence of antigenic stimuli. Nef activates Rac by binding the DOCK2-ELMO1 complex, and this interaction is linked to the abilities of Nef to inhibit chemotaxis and promote T cell activation. Our data indicate that Nef targets a critical switch that regulates Rac GTPases downstream of chemokine- and antigen-initiated signaling pathways. This interaction enables Nef to influence multiple aspects of T cell function and thus provides an important mechanism by which Nef impacts pathogenesis by primate lentiviruses.

  1. Cooperative Optimization QoS Cloud Routing Protocol Based on Bacterial Opportunistic Foraging and Chemotaxis Perception for Mobile Internet

    Directory of Open Access Journals (Sweden)

    Shujuan Wang

    2015-01-01

    Full Text Available In order to strengthen the mobile Internet mobility management and cloud platform resources utilization, optimizing the cloud routing efficiency is established, based on opportunistic bacterial foraging bionics, and puts forward a chemotaxis perception of collaborative optimization QoS (Quality of Services cloud routing mechanism. The cloud routing mechanism is based on bacterial opportunity to feed and bacterial motility and to establish the data transmission and forwarding of the bacterial population behavior characteristics. This mechanism is based on the characteristics of drug resistance of bacteria and the structure of the field, and through many iterations of the individual behavior and population behavior the bacteria can be spread to the food gathering area with a certain probability. Finally, QoS cloud routing path would be selected and optimized based on bacterial bionic optimization and hedge mapping relationship between mobile Internet node and bacterial population evolution iterations. Experimental results show that, compared with the standard dynamic routing schemes, the proposed scheme has shorter transmission delay, lower packet error ratio, QoS cloud routing loading, and QoS cloud route request overhead.

  2. Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

    Directory of Open Access Journals (Sweden)

    Kyler B Pallister

    Full Text Available In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

  3. Innate positive chemotaxis to pollen from crops and banker plants in predaceous biological control agents: towards new field lures?

    Science.gov (United States)

    Li, Shu; Tan, Xiaoling; Desneux, Nicolas; Benelli, Giovanni; Zhao, Jing; Li, Xinhai; Zhang, Fan; Gao, Xiwu; Wang, Su

    2015-01-01

    Predator-prey interactions form the core of biological control of arthropod pests. Which tools can be used to monitor and collect carnivorous arthropods in natural habitats and targeted crops? Eco-friendly and effective field lures are urgently needed. In this research, we carried out olfactometer experiments assess innate positive chemotaxis to pollen of seven crop and banker plant by two important predatory biological control agents: the coccinellid Propylea japonica (Thunberg) and the anthocorid Orius sauteri (Poppius). We compared the attractiveness of pollens from crops and banker plants to that of common prey homogenates (aphids and thrips, respectively). Attractiveness of the tested odor sources was checked via field trapping experiments conducted in organic apple orchards and by release-recapture assays in organic greenhouse tomato crops. Maize and canola pollen were attractive to both P. japonica and O. sauteri, in laboratory and field assays. P. japonica was highly attracted by balm mint pollen, whereas O. sauteri was attracted by alfalfa pollen. Our results encourage the use of pollen from crops and banker plants as low-cost and eco-friendly attractors to enhance the monitoring and attraction of arthropod predators in biological control programs. PMID:26235136

  4. The Molecular Identities of the Caenorhabditis elegans Intraflagellar Transport Genes dyf-6, daf-10 and osm-1

    OpenAIRE

    Bell, Leslie R.; Stone, Steven; Yochem, John; Shaw, Jocelyn E.; Herman, Robert K.

    2006-01-01

    The Caenorhabditis elegans genes dyf-6, daf-10, and osm-1 are among the set of genes that affect chemotaxis and the ability of certain sensory neurons to take up fluorescent dyes from the environment. Some genes in this category are known to be required for intraflagellar transport (IFT), which is the bidirectional movement of raft-like particles along the axonemes of cilia and flagella. The cloning of dyf-6, daf-10, and osm-1 are described here. The daf-10 and osm-1 gene products resemble ea...

  5. EFFECT OF FERULIC ACID ON CHEMOTAXIS AND NODULATION OF Bradyrhizobium japonicum

    OpenAIRE

    María C. Nápoles; A. Gutiérrez; E. Bordallo; Hernández, R.

    2001-01-01

    En este trabajo se estudió el efecto de tres concentraciones de ácido ferúlico sobre la quimiotaxis y la nodulación de B. japonicum ICA 8001. También se evaluó el efecto de este ácido hidroxicinámico obtenido a partir de vainillina, así como su capacidad de inducción sobre los genes de nodulación mediante la detección de factores Nod sintetizados. Se obtuvo una actividad quimiotáctica positiva pero no fuerte y solamente 10 mM como componente del medio de cultivo mostró una influencia positiva...

  6. EFFECT OF FERULIC ACID ON CHEMOTAXIS AND NODULATION OF Bradyrhizobium japonicum

    Directory of Open Access Journals (Sweden)

    María C. Nápoles

    2001-01-01

    Full Text Available En este trabajo se estudió el efecto de tres concentraciones de ácido ferúlico sobre la quimiotaxis y la nodulación de B. japonicum ICA 8001. También se evaluó el efecto de este ácido hidroxicinámico obtenido a partir de vainillina, así como su capacidad de inducción sobre los genes de nodulación mediante la detección de factores Nod sintetizados. Se obtuvo una actividad quimiotáctica positiva pero no fuerte y solamente 10 mM como componente del medio de cultivo mostró una influencia positiva sobre la nodulación. El ácido ferúlico sintetizado a partir de vainillina incrementó todos los parámetros de la nodulación. La actividad nod inductora de este ácido se evidenció con la producción de cuatro estructuras de lipoquitinoligosacáridos.

  7. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  8. Site-specific and synergistic stimulation of methylation on the bacterial chemotaxis receptor Tsr by serine and CheW

    Directory of Open Access Journals (Sweden)

    Weis Robert M

    2005-03-01

    Full Text Available Abstract Background Specific glutamates in the methyl-accepting chemotaxis proteins (MCPs of Escherichia coli are modified during sensory adaptation. Attractants that bind to MCPs are known to increase the rate of receptor modification, as with serine and the serine receptor (Tsr, which contributes to an increase in the steady-state (adapted methylation level. However, MCPs form ternary complexes with two cytoplasmic signaling proteins, the kinase (CheA and an adaptor protein (CheW, but their influences on receptor methylation are unknown. Here, the influence of CheW on the rate of Tsr methylation has been studied to identify contributions to the process of adaptation. Results Methyl group incorporation was measured in a series of membrane samples in which the Tsr molecules were engineered to have one available methyl-accepting glutamate residue (297, 304, 311 or 493. The relative rates at these sites (0.14, 0.05, 0.05 and 1, respectively differed from those found previously for the aspartate receptor (Tar, which was in part due to sequence differences between Tar and Tsr near site four. The addition of CheW generated unexpectedly large and site-specific rate increases, equal to or larger than the increases produced by serine. The increases produced by serine and CheW (added separately were the largest at site one, ~3 and 6-fold, respectively, and the least at site four, no change and ~2-fold, respectively. The rate increases were even larger when serine and CheW were added together, larger than the sums of the increases produced by serine and CheW added separately (except site four. This resulted in substantially larger serine-stimulated increases when CheW was present. Also, CheW enhanced methylation rates when either two or all four sites were available. Conclusion The increase in the rate of receptor methylation upon CheW binding contributes significantly to the ligand specificity and kinetics of sensory adaptation. The synergistic effect of

  9. Characterization of Cell Surface and EPS Remodeling of Azospirillum brasilense Chemotaxis-like 1 Signal Transduction Pathway mutants by Atomic Force Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Billings, Amanda N [ORNL; Siuti, Piro [ORNL; Bible, Amber [University of Tennessee, Knoxville (UTK); Alexandre, Gladys [University of Tennessee, Knoxville (UTK); Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL; Morrell-Falvey, Jennifer L [ORNL

    2011-01-01

    To compete in complex microbial communities, bacteria must quickly sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the modulation of multiple cellular responses, including motility, EPS production, and cell-to-cell interactions. Recently, the Che1 chemotaxis-like pathway from Azospirillum brasilense was shown to modulate flocculation. In A. brasilense, cell surface properties, including EPS production, are thought to play a direct role in promoting flocculation. Using atomic force microscopy (AFM), we have detected distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains that are absent in the wild type strain. Whereas the wild type strain produces a smooth mucosal extracellular matrix, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition and lectin-binding assays suggest that the composition of EPS components in the extracellular matrix differs between the cheA1 and cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that mutations in the Che1 pathway that result in increased flocculation are correlated with distinctive changes in the extracellular matrix structure produced by the mutants, including likely changes in the EPS structure and/or composition.

  10. Characterization of cell surface and extracellular matrix remodeling of Azospirillum brasilense chemotaxis-like 1 signal transduction pathway mutants by atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Doktycz, Mitchel John [ORNL; Morrell-Falvey, Jennifer L [ORNL

    2011-01-01

    To compete in complex microbial communities, bacteria must sense environmental changes and adjust cellular functions for optimal growth. Chemotaxis-like signal transduction pathways are implicated in the regulation of multiple behaviors in response to changes in the environment, including motility patterns, exopolysaccharide production, and cell-to-cell interactions. In Azospirillum brasilense, cell surface properties, including exopolysaccharide production, are thought to play a direct role in promoting flocculation. Recently, the Che1 chemotaxis-like pathway from A. brasilense was shown to modulate flocculation, suggesting an associated modulation of cell surface properties. Using atomic force microscopy, distinct changes in the surface morphology of flocculating A. brasilense Che1 mutant strains were detected. Whereas the wild-type strain produces a smooth mucosal extracellular matrix after 24 h, the flocculating Che1 mutant strains produce distinctive extracellular fibril structures. Further analyses using flocculation inhibition, lectin-binding assays, and comparison of lipopolysaccharides profiles suggest that the extracellular matrix differs between the cheA1 and the cheY1 mutants, despite an apparent similarity in the macroscopic floc structures. Collectively, these data indicate that disruption of the Che1 pathway is correlated with distinctive changes in the extracellular matrix, which likely result from changes in surface polysaccharides structure and/or composition.

  11. Enhanced human neutrophil vitamin C status, chemotaxis and oxidant generation following dietary supplementation with vitamin C-rich SunGold kiwifruit.

    Science.gov (United States)

    Bozonet, Stephanie M; Carr, Anitra C; Pullar, Juliet M; Vissers, Margreet C M

    2015-04-01

    Neutrophils are the body's primary defenders against invading pathogens. These cells migrate to loci of infection where they engulf micro-organisms and subject them to an array of reactive oxygen species and antimicrobial proteins to effect killing. Spent neutrophils subsequently undergo apoptosis and are cleared by macrophages, thereby resolving the inflammatory episode. Neutrophils contain high concentrations of vitamin C (ascorbate) and this is thought to be essential for their function. This may be one mechanism whereby vitamin C enhances immune function. The aim of our study was to assess the effect of dietary supplementation with vitamin C-rich SunGold kiwifruit on four important functions of neutrophils: chemotaxis, oxidant generation, extracellular trap formation, and apoptosis. Fourteen young men (aged 18-30 years) with suboptimal plasma vitamin C status (70 μmol/L (p < 0.001) within one week of supplementation and there was a significant increase in neutrophil vitamin C status following four weeks' intervention (p = 0.016). We observed a significant 20% increase in neutrophil chemotaxis post-intervention (p = 0.041) and also a comparable increase in oxidant generation (p = 0.031). Supplementation did not affect neutrophil extracellular trap formation or spontaneous apoptosis. Our data indicate that supplementation with vitamin C-rich kiwifruit is associated with improvement of important neutrophil functions, which would be expected to translate into enhanced immunity. PMID:25912037

  12. Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice

    Directory of Open Access Journals (Sweden)

    Badr Gamal

    2011-11-01

    Full Text Available Abstract Background Long and persistent uncontrolled diabetes tends to degenerate the immune system and leads to an increased incidence of infection. Whey proteins (WPs enhance immunity during early life and have a protective role in some immune disorders. In this study, the effects of camel WP on the chemotaxis of B and T cells to CXCL12 and CCL21 in diabetic mice were investigated. Results Flow cytometric analysis of the surface expressions of CXCR4 (CXCL12 receptor and CCR7 (CCL21 receptor on B and T cells revealed that the surface expressions of CXCR4 and CCR7 were not significantly altered in diabetic and WP-supplemented diabetic mice compared with control mice. Nevertheless, B and T lymphocytes from diabetic mice were found to be in a stunned state, with a marked and significant (P Conclusion Our data revealed the benefits of WP supplementation in enhancing cytoskeletal rearrangement and chemotaxis in B and T cells, and subsequently improving the immune response in diabetic mice.

  13. Variation of chemosensory receptor content of Campylobacter jejuni strains and modulation of receptor gene expression under different in vivo and in vitro growth conditions

    Directory of Open Access Journals (Sweden)

    Day Christopher J

    2012-06-01

    Full Text Available Abstract Background Chemotaxis is crucial for the colonisation/infection of hosts with Campylobacter jejuni. Central to chemotaxis are the group A chemotaxis genes that are responsible for sensing the external environment. The distribution of group A chemoreceptor genes, as found in the C. jejuni sequenced strains, tlp1-4, 7, 10 and 11 were determined in 33 clinical human and avian isolates. Results Group A tlp gene content varied among the strains with genes encoding tlp1 (aspartate receptor, ccaA and tlp7 present in all strains tested, where as tlp11 was present in only one of our international collection clinical isolates, C. jejuni 520, but was more prevalent (9/13 in the freshly isolated clinical stains from patients who required hospitalisation due to C. jejuni infection (GCH1-17. Relative expression levels of the group A tlp genes were also determined in C. jejuni reference strains NCTC 11168-GS, 11168-O and 81116 using cells grown in vitro at 37°C, 42°C and maintained at room temperature and with cells isolated directly from murine and avian hosts by immune magnetic separation without subsequent culture. Gene expression of tlp genes was varied based on strain, growth conditions and in vivo isolation source. Tlp1, although the most conserved, showed the lowest and most varied mRNA expression and protein production under laboratory conditions. Tlp7 was highly expressed at most conditions tested, and gene expression was not influenced by the tlp7 gene encoding a full length protein or one expressed as separate periplasmic and cytoplasmic domains. Conclusion We have shown that chemosensory receptor set variation exists among C. jejuni strains, but is not dependent on the isolation source.

  14. Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

    DEFF Research Database (Denmark)

    Jinquan, T; Frydenberg, Jane; Mukaida, N;

    1995-01-01

    activate neutrophils, whereas it induces chemotaxis, exocytosis, and a respiratory burst in neutrophils. To date, its functions on T lymphocytes have not been well established. We report here that recombinant human (rh)GRO-alpha is a potent chemoattractant for freshly isolated T lymphocytes, but not for...

  15. TGF-β1 blockade of microglial chemotaxis toward Aβ aggregates involves SMAD signaling and down-regulation of CCL5

    Directory of Open Access Journals (Sweden)

    Huang Fong-Lee

    2010-04-01

    Full Text Available Abstract Background Overactivated microglia that cluster at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in Alzheimer's disease (AD. Therefore, attenuating microglial clustering can reduce focal neuroinflammation at neuritic plaques. Previously, we identified CCL5 and CCL2 as prominent chemokines that mediate the chemotaxis of microglia toward beta-amyloid (Aβaggregates. Although transforming growth factor-β1 (TGF-β1 has been shown to down-regulate the expression of chemokines in activated microglia, whether TGF-β1 can reduce the chemotaxis of microglia toward neuritic plaques in AD remains unclear. Methods In the present study, we investigated the effects of TGF-β1 on Aβ-induced chemotactic migration of BV-2 microglia using time-lapse recording, transwell assay, real-time PCR, ELISA, and western blotting. Results The cell tracing results suggest that the morphological characteristics and migratory patterns of BV-2 microglia resemble those of microglia in slice cultures. Using this model system, we discovered that TGF-β1 reduces Aβ-induced BV-2 microglial clustering in a dose-dependent manner. Chemotactic migration of these microglial cells toward Aβ aggregates was significantly attenuated by TGF-β1. However, these microglia remained actively moving without any reduction in migration speed. Pharmacological blockade of TGF-β1 receptor I (ALK5 by SB431542 treatment reduced the inhibitory effects of TGF-β1 on Aβ-induced BV-2 microglial clustering, while preventing TGF-β1-mediated cellular events, including SMAD2 phosphorylation and CCL5 down-regulation. Conclusions Our results suggest that TGF-β1 reduces Aβ-induced microglial chemotaxis via the SMAD2 pathway. The down-regulation of CCL5 by TGF-β1 at least partially contributes to the clustering of microglia at Aβ aggregates. The attenuating effects of SB431542 upon TGF-β1-suppressed microglial clustering may be

  16. Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases

    DEFF Research Database (Denmark)

    Kampen, G T; Stafford, S; Adachi, T;

    2000-01-01

    Eotaxin and other CC chemokines acting via CC chemokine receptor-3 (CCR3) are believed to play an integral role in the development of eosinophilic inflammation in asthma and allergic inflammatory diseases. However, little is known about the intracellular events following agonist binding to CCR3 and...... the relationship of these events to the functional response of the cell. The objectives of this study were to investigate CCR3-mediated activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase-2 (ERK2), p38, and c-jun N-terminal kinase (JNK) in eosinophils and to...... assess the requirement for MAP kinases in eotaxin-induced eosinophil cationic protein (ECP) release and chemotaxis. MAP kinase activation was studied in eotaxin-stimulated eosinophils (more than 97% purity) by Western blotting and immune-complex kinase assays. ECP release was measured by radioimmunoassay...

  17. Evidence of chemotaxis by quantitative measurement of the force vectors of Trypanossoma cruzi in the vicinity of the Rhodnius prolixus midgut wall cell

    Science.gov (United States)

    de Thomaz, A. A.; Almeida, D. B.; Fontes, A.; Stahl, C. V.; Santos-Mallet, J. R.; Gomes, S. A. O.; Feder, D.; Cesar, C. L.

    2009-08-01

    In this work we used a methodology to study chemotaxis of Trypanossoma cruzi (T. Cruzi) in real time using an Optical Tweezers system. Trapped beads were used as a force transducer for measuring forces of the same order of magnitude as typical forces induced by flagellar motion. Optical Tweezers allowed real time measurements of the force vectors, strength and direction, of living parasites under chemical or other kinds of gradients. This seems to be the ideal tool to perform observations of taxis response of cells and microorganisms with high sensitivity to capture instantaneous responses to a given stimulus. We applied this methodology to investigate the T. cruzi under distinct situations: the parasite alone and in the presence of its insect-vector Rhodnius prolixus (R. prolixus).

  18. A computational method for the coupled solution of reaction-diffusion equations on evolving domains and manifolds: Application to a model of cell migration and chemotaxis

    Science.gov (United States)

    MacDonald, G.; Mackenzie, J. A.; Nolan, M.; Insall, R. H.

    2016-03-01

    In this paper, we devise a moving mesh finite element method for the approximate solution of coupled bulk-surface reaction-diffusion equations on an evolving two dimensional domain. Fundamental to the success of the method is the robust generation of bulk and surface meshes. For this purpose, we use a novel moving mesh partial differential equation (MMPDE) approach. The developed method is applied to model problems with known analytical solutions; these experiments indicate second-order spatial and temporal accuracy. Coupled bulk-surface problems occur frequently in many areas; in particular, in the modelling of eukaryotic cell migration and chemotaxis. We apply the method to a model of the two-way interaction of a migrating cell in a chemotactic field, where the bulk region corresponds to the extracellular region and the surface to the cell membrane.

  19. Cross-talk between Tetraspanin CD9 and Transmembrane Adaptor Protein Non-T Cell Activation Linker (NTAL) in Mast Cell Activation and Chemotaxis

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Bambousková, Monika; Machyna, Martin; Stegurová, Lucie; Smrž, Daniel; Dráber, Petr

    2013-01-01

    Roč. 288, č. 14 (2013), s. 9801-9814. ISSN 0021-9258 R&D Projects: GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GD204/09/H084; GA MŠk LD12073; GA TA ČR TA01010436; GA MPO FR-TI3/067 Grant ostatní: European Cooperation in Science and Technology(XE) Action BM1007 Institutional support: RVO:68378050 Keywords : mast cell * chemotaxis * Fc receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.600, year: 2013

  20. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

    Directory of Open Access Journals (Sweden)

    Carolina V Messias

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5. S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts.

  1. Enhanced Human Neutrophil Vitamin C Status, Chemotaxis and Oxidant Generation Following Dietary Supplementation with Vitamin C-Rich SunGold Kiwifruit

    Directory of Open Access Journals (Sweden)

    Stephanie M. Bozonet

    2015-04-01

    Full Text Available Neutrophils are the body’s primary defenders against invading pathogens. These cells migrate to loci of infection where they engulf micro-organisms and subject them to an array of reactive oxygen species and antimicrobial proteins to effect killing. Spent neutrophils subsequently undergo apoptosis and are cleared by macrophages, thereby resolving the inflammatory episode. Neutrophils contain high concentrations of vitamin C (ascorbate and this is thought to be essential for their function. This may be one mechanism whereby vitamin C enhances immune function. The aim of our study was to assess the effect of dietary supplementation with vitamin C-rich SunGold kiwifruit on four important functions of neutrophils: chemotaxis, oxidant generation, extracellular trap formation, and apoptosis. Fourteen young men (aged 18–30 years with suboptimal plasma vitamin C status (<50 μmol/L were supplemented for four weeks with two SunGold kiwifruit/day. Plasma vitamin C status was monitored weekly and neutrophil vitamin C levels were assessed at baseline and post-intervention. Neutrophil function assays were carried out on cells isolated at baseline and post-intervention. Plasma vitamin C levels increased to >70 μmol/L (p < 0.001 within one week of supplementation and there was a significant increase in neutrophil vitamin C status following four weeks’ intervention (p = 0.016. We observed a significant 20% increase in neutrophil chemotaxis post-intervention (p = 0.041 and also a comparable increase in oxidant generation (p = 0.031. Supplementation did not affect neutrophil extracellular trap formation or spontaneous apoptosis. Our data indicate that supplementation with vitamin C-rich kiwifruit is associated with improvement of important neutrophil functions, which would be expected to translate into enhanced immunity.

  2. Artificial Bee Colony with Chemotaxis Behavior for Training Artificial Neural Network%趋药性人工蜂群算法训练神经网络研究

    Institute of Scientific and Technical Information of China (English)

    林晓宇; 钟一文; 王爱荣

    2011-01-01

    A hybird artificial bee colony named ABC-CB (artificial bee colony with chemotaxis behavior) is presented to imporve the local exploitation ability of ABC. Chemotaxis behavior of bacterial foraging optimization algorithm is embedded into ABC in exploitation process to make employed bees and onlookers tumble to the best dimension and swim for several steps just like what the bacteria do while foraging. On the other hand,bees try all dimensions and select the best one to move. The simulation experiments carried out on the training of artificial neural network show that the proposed algorithm has better performance than bee colony optimization algorithm and particle swarm optimization algorithm.%本文设计了一种复合人工蜂群算法,将细菌觅食优化算法中的趋药性行为引入到人工蜂群算法中,使得引领蜂和观察蜂进行局部探查时像细菌觅食时那样翻转到有利的方向上进行游动;另一方面,让蜜蜂尝试在所有维度产生扰动并择优选择,这两种策略大大增强了人工蜂群算法的局部探查能力.将此算法应用于训练人工神经网络,实验表明改进后的算法性能比人工蜂群算法和粒子群算法有很大提高.

  3. The Internal Phosphodiesterase RegA Is Essential for the Suppression of Lateral Pseudopods during Dictyostelium Chemotaxis

    OpenAIRE

    Wessels, Deborah J.; Zhang, Hui; Reynolds, Joshua; Daniels, Karla; Heid, Paul; Lu, Sijie; Kuspa, Adam; Shaulsky, Gad; Loomis, William F.; Soll, David R.

    2000-01-01

    Dictyostelium strains in which the gene encoding the cytoplasmic cAMP phosphodiesterase RegA is inactivated form small aggregates. This defect was corrected by introducing copies of the wild-type regA gene, indicating that the defect was solely the consequence of the loss of the phosphodiesterase. Using a computer-assisted motion analysis system, regA− mutant cells were found to show little sense of direction during aggregation. When labeled wild-type cells wer...

  4. Characterization of che W Genes of Leptospira interrogans and Their Effects in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Zhen-Hong LI; Ke DONG; Jing-Chun SUN; Jian-Ping YUAN; Bao-Yu HU; Jing-Xing LIU; Guo-Ping ZHAO; Xiao-Kui GUO

    2006-01-01

    The motility and chemotaxis systems are critical for the virulence of leptospires. In this study,the phylogenetic profiles method was used to predict the interaction of chemotaxis proteins. It was shown that CheW1 links to CheA1, CheY, CheB and CheW2; CheW3 links to CheA2, MCP (LA2426), CheB3 and CheD1; and CheW2 links only to CheW1. The similarity analysis demonstrated that CheW2 of Leptospira interrogans strain Lai had poor homology with CheW of Escherichia coli in the region of residues 30-50. In order to verify the function of these proteins, the putative cheW genes were cloned into pQE31 vector and expressed in wild-type E. coli strain RP437 or cheW defective strain RP4606. The swarming results indicated that CheW1 and CheW3 could restore swarming of RP4606 while CheW2 could not. Overexpression of CheW1 and CheW3 in RP437 inhibited the swarming of RP437, whereas the inhibitory effect of CheW2 was much lower. Therefore, we presumed that CheW1 and CheW3 might have the function of CheW whileCheW2 does not. The existence of multiple copies of chemotaxis homologue genes suggested that L.interrogans strain Lai might have a more complex chemosensory pathway.

  5. The IplA Ca2+ channel of Dictyostelium discoideum is necessary for chemotaxis mediated through Ca2+, but not through cAMP, and has a fundamental role in natural aggregation

    OpenAIRE

    Lusche, Daniel F.; Wessels, Deborah; Scherer, Amanda; Daniels, Karla; Kuhl, Spencer; Soll, David R.

    2012-01-01

    During aggregation of Dictyostelium discoideum, nondissipating, symmetrical, outwardly moving waves of cAMP direct cells towards aggregation centers. It has been assumed that the spatial and temporal characteristics of the front and back of each cAMP wave regulate both chemokinesis and chemotaxis. However, during the period preceding aggregation, cells acquire not only the capacity to chemotax in a spatial gradient of cAMP, but also in a spatial gradient of Ca2+. The null mutant of the putati...

  6. A model for cell type localization in the migrating slug of Dictyostelium discoideum based on differential chemotactic sensitivity to cAMP and differential sensitivity to suppression of chemotaxis by ammonia

    Indian Academy of Sciences (India)

    Ira N Feit; Jeffrey Pawlikowski; Caroline Zawilski

    2007-03-01

    The three basic cell types in the migrating slug of Dictyostelium discoideum show differential chemotactic response to cyclic AMP (cAMP) and differential sensitivity to suppression of the chemotaxis by ammonia. The values of these parameters indicate a progressive maturation of chemotactic properties during the transdifferentiation of slug cell types. We present a model that explains the localization of the three cell types within the slug based on these chemotactic differences and on the maturation of their chemotactic properties.

  7. Role of Shwachman-Bodian-Diamond syndrome protein in translation machinery and cell chemotaxis: a comparative genomics approach

    OpenAIRE

    Vasieva O

    2011-01-01

    Olga VasievaInstitute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; Fellowship for the Interpretation of Genomes, Burr Ridge, IL, USAAbstract: Shwachman-Bodian-Diamond syndrome (SBDS) is linked to a mutation in a single gene. The SBDS proinvolved in RNA metabolism and ribosome-associated functions, but SBDS mutation is primarily linked to a defect in polymorphonuclear leukocytes unable to orient correctly in a spatial gradient of chemoattractants. Results of data...

  8. "In vivo" leukocyte chemotaxis in experimental mice Schistosoma mansoni infection Quimiotaxia de leucócitos "in vivo" na infecção experimental por Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Kirte Maria Teixeira

    1994-06-01

    Full Text Available The "in vivo" chemotaxis was studied in C57B1/10 mice 10, 30, 50 and 60 days after a Schistosoma mansoni infection in comparison to a control group (uninfected mice. Staphylococcal protein A was injected into a connective tissue air pouch of control and experimental mice and the leukocyte chemotaxis was counted. A decrease in polymorphonuclear (PMN leukocyte response was found in infected mice in comparison to the control group (pA quimiotaxia de leucócitos "in vivo" foi avaliada em camundongos da linhagem C57B1/10 e estudada 10, 30, 50 e 60 dias após a infecção por Schistosoma mansoni. A proteína A foi utilizada como quimiotático e injetada no tecido conjuntivo no dorso dos camundongos dos grupos experimentais e controle. Nos grupos experimentais foi observado uma diminuição na resposta dos leucócitos polimorfonucleares (PMN em comparação com o grupo controle (p<0.05. Os camundongos estudados 10 dias após a infecção, mostraram uma diminuição na resposta quimiotática de leucócitos PMN, comparando com o grupo controle (p<0.05 e este dado tornou-se mais evidente nos grupos experimentais estudados 30 e 50 dias após a infecção. Apesar da resposta quimiotática dos leucócitos PMN nos camundongos estudados 60 dias após a infecção aumentarem em comparação aos animais analisados 50 dias após a infecção, este aumento foi bem menor em relação ao grupo controle. A resposta quimiotática dos mononucleares não apresentou diferença significativa entre camundongos experimentais e controles

  9. HIV-1 infected lymphoid organs upregulate expression and release of the cleaved form of uPAR that modulates chemotaxis and virus expression.

    Directory of Open Access Journals (Sweden)

    Manuela Nebuloni

    Full Text Available Cell-associated receptor for urokinase plasminogen activator (uPAR is released as both full-length soluble uPAR (suPAR and cleaved (c-suPAR form that maintain ability to bind to integrins and other receptors, thus triggering and modulating cell signaling responses. Concerning HIV-1 infection, plasma levels of suPAR have been correlated with the severity of disease, levels of immune activation and ineffective immune recovery also in individuals receiving combination anti-retroviral therapy (cART. However, it is unknown whether and which suPAR forms might contribute to HIV-1 induced pathogenesis and to the related state of immune activation. In this regard, lymphoid organs represent an import site of chronic immune activation and virus persistence even in individuals receiving cART. Lymphoid organs of HIV-1(+ individuals showed an enhanced number of follicular dendritic cells, macrophages and endothelial cells expressing the cell-associated uPAR in comparison to those of uninfected individuals. In order to investigate the potential role of suPAR forms in HIV-1 infection of secondary lymphoid organs, tonsil histocultures were established from HIV-1 seronegative individuals and infected ex vivo with CCR5- and CXCR4-dependent HIV-1 strains. The levels of suPAR and c-suPAR were significantly increased in HIV-infected tonsil histocultures supernatants in comparison to autologous uninfected histocultures. Supernatants from infected and uninfected cultures before and after immunodepletion of suPAR forms were incubated with the chronically infected promonocytic U1 cell line characterized by a state of proviral latency in unstimulated conditions. In the contest of HIV-conditioned supernatants we established that c-suPAR, but not suPAR, inhibited chemotaxis and induced virus expression in U1 cells. In conclusion, lymphoid organs are an important site of production and release of both suPAR and c-suPAR, this latter form being endowed with the capacity of

  10. Overactivation of phospholipase C-gamma1 renders platelet-derived growth factor beta-receptor-expressing cells independent of the phosphatidylinositol 3-kinase pathway for chemotaxis

    DEFF Research Database (Denmark)

    Rönnstrand, L; Siegbahn, A; Rorsman, C;

    1999-01-01

    ., Siegbahn, A. , Rorsman, C., Engström, U., Wernstedt, C., Heldin, C.-H., and Rönnstrand, L. (1996) EMBO J. 15, 5299-5313). Here we show that the increased chemotaxis correlates with increased activation of phospholipase C-gamma1 (PLC-gamma1), measured as inositol-1,4, 5-trisphosphate release. By two......-dimensional phosphopeptide mapping, the increase in phosphorylation of PLC-gamma1 was shown not to be selective for any site, rather a general increase in phosphorylation of PLC-gamma1 was seen. Specific inhibitors of protein kinase C, bisindolylmaleimide (GF109203X), and phosphatidylinositol 3-kinase (PI3-kinase), LY294002......, did not affect the activation of PLC-gamma1. To assess whether increased activation of PLC-gamma1 is the cause of the hyperchemotactic behavior of the Y934F mutant cell line, we constructed cell lines expressing either wild-type or a catalytically compromised version of PLC-gamma1 under a tetracycline...

  11. Quantitative Phosphoproteome Analysis of Lysophosphatidic Acid Induced Chemotaxis applying Dual-step ¹⁸O Labeling Coupled with Immobilized Metal-ion Affinity Chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Shi-Jian; Wang, Yingchun; Jacobs, Jon M.; Qian, Weijun; Yang, Feng; Tolmachev, Aleksey V.; Du, Xiuxia; Wang, Wei; Moore, Ronald J.; Monroe, Matthew E.; Purvine, Samuel O.; Waters, Katrina M.; Heibeck, Tyler H.; Adkins, Joshua N.; Camp, David G.; Klemke, Richard L.; Smith, Richard D.

    2008-10-01

    Reversible protein phosphorylation is a central cellular regulatory mechanism in modulating protein activity and propagating signals within cellular pathways and networks. Development of more effective methods for the simultaneous identification of phosphorylation sites and quantification of temporal changes in protein phosphorylation could provide important insights into molecular signaling mechanisms in a variety of different cellular processes. Here we present an integrated quantitative phosphoproteomics approach and its applications for comparative analysis of Cos-7 cells in response to lysophosphatidic acid (LPA) gradient stimulation. The approach combines trypsin-catalyzed 16O/18O labeling plus 16O/18O-methanol esterification labeling for quantitation, a macro- Immobilized Metal-ion Affinity Chromatography trap for phosphopeptide enrichment, and a monolithic capillary column with integrated electrospray emitter. LC separation and MS/MS is followed by neutral loss-dependent MS/MS/MS for phosphopeptide identification using a linear ion trap (LTQ)-FT mass spectrometer and complementary searching algorithms for interpreting MS/MS spectra. Protein phosphorylation involved in various signaling pathways of cell migration were identified and quantified, such as mitogen-activated protein kinase 1, dual-specificity mitogen-activated protein kinase kinase 2, and dual-specificity tyrosine-phosphorylation regulated kinase 1b, and a number of Rho GTPase-activating proteins. These results demonstrate the efficiency of this quantitative phosphoproteomics approach and its application for rapid discovery of phosphorylation events associated with gradient sensing and cell chemotaxis.

  12. Analysis of periplasmic sensor domains from Anaeromyxobacter dehalogenans 2CP-C: structure of one sensor domain from a histidine kinase and another from a chemotaxis protein.

    Science.gov (United States)

    Pokkuluri, P Raj; Dwulit-Smith, Jeff; Duke, Norma E; Wilton, Rosemarie; Mack, Jamey C; Bearden, Jessica; Rakowski, Ella; Babnigg, Gyorgy; Szurmant, Hendrik; Joachimiak, Andrzej; Schiffer, Marianne

    2013-10-01

    Anaeromyxobacter dehalogenans is a δ-proteobacterium found in diverse soils and sediments. It is of interest in bioremediation efforts due to its dechlorination and metal-reducing capabilities. To gain an understanding on A. dehalogenans' abilities to adapt to diverse environments we analyzed its signal transduction proteins. The A. dehalogenans genome codes for a large number of sensor histidine kinases (HK) and methyl-accepting chemotaxis proteins (MCP); among these 23 HK and 11 MCP proteins have a sensor domain in the periplasm. These proteins most likely contribute to adaptation to the organism's surroundings. We predicted their three-dimensional folds and determined the structures of two of the periplasmic sensor domains by X-ray diffraction. Most of the domains are predicted to have either PAS-like or helical bundle structures, with two predicted to have solute-binding protein fold, and another predicted to have a 6-phosphogluconolactonase like fold. Atomic structures of two sensor domains confirmed the respective fold predictions. The Adeh_2942 sensor (HK) was found to have a helical bundle structure, and the Adeh_3718 sensor (MCP) has a PAS-like structure. Interestingly, the Adeh_3718 sensor has an acetate moiety bound in a binding site typical for PAS-like domains. Future work is needed to determine whether Adeh_3718 is involved in acetate sensing by A. dehalogenans. PMID:23897711

  13. Reduced Expression of Galectin-9 Contributes to a Poor Outcome in Colon Cancer by Inhibiting NK Cell Chemotaxis Partially through the Rho/ROCK1 Signaling Pathway.

    Science.gov (United States)

    Wang, Yang; Sun, Jintang; Ma, Chao; Gao, Wenjuan; Song, Bingfeng; Xue, Hao; Chen, Weiliang; Chen, Xi; Zhang, Yun; Shao, Qianqian; Wang, Qingjie; Zhao, Lei; Liu, Jia; Wang, Xiuwen; Wang, Huayang; Zhang, Yun; Yang, Meixiang; Qu, Xun

    2016-01-01

    Galectin-9 is a widely expressed protein that is involved in immune regulation and tumorpathogenesis and serves as a marker of a poor prognosis in various types of cancers. However, the clinical impact and the precise mechanism by which this protein contributes to colon tumor progression are unclear. In the present study, we detected the expression of galectin-9 and CD56 cells using immunohistochemistry. Spearman's rank correlation was used to clarify the association between galectin-9 expression and natural killer (NK) cell infiltration. The influence of galectin-9 on NK-92 cell migration was evaluated in vitro using transwell chemotaxis assays. The role of rh-galectin-9 in F-actin polarization in NK-92 cells was investigated using laser scanning confocal microscopy. We showed that galectin-9 was expressed in 101 (78.91%) colon tumor tissues and that was expressed at lower levels in these tissues than in para-tumor tissues. Low levels of galectin-9 expression were positively correlated with a poor histological grade and lymph node metastasis (Ppolarization through the Rho/ROCK1 signaling pathway. These results suggest that galectin-9 expression potentially represents a novel mechanism for tumors to escape immune surveillance in colon tumors. PMID:27028892

  14. EphrinB1 and EphrinB2 regulate T cell chemotaxis and migration in experimental autoimmune encephalomyelitis and multiple sclerosis.

    Science.gov (United States)

    Luo, Hongyu; Broux, Bieke; Wang, Xuehai; Hu, Yan; Ghannam, Soufiane; Jin, Wei; Larochelle, Catherine; Prat, Alexandre; Wu, Jiangping

    2016-07-01

    T cells are believed to be key effector cells in multiple sclerosis (MS). In this study, we examined the roles of T cell ephrinB1 (EFNB1) and ephrinB2 (EFNB2) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and MS. We provide evidence that animals with T cell specific double deletion of EFNB1 and EFNB2 (dKO) have reduced proliferation in response to MOG35-55, defective Th1 and Th17 differentiations and significantly lower scores of MOG-induced EAE. We further demonstrate that dKO T cells are compromised in their ability to migrate into the CNS of EAE animals in vivo and towards multiple chemokines in vitro. Using deletion mutations, we identified a critical 11-aa EFNB1 intracellular domain segment that controls T cell chemotaxis towards CCL21. In humans, EFNB1 and EFNB2 are highly expressed in Th1 and Th17 cells and EFNB1- and EFNB2-expressing T cells are found among immune cell infiltrates in MS lesions. Reverse signaling through EFNB1 and EFNB2 in human Th17 cells enhances their migration through a monolayer of blood brain barrier endothelial cells. Our study demonstrates that expression of EFNB1 and EFNB2 is implicated in Th cell differentiation and migration to inflammatory sites in both EAE and MS. PMID:27039370

  15. Enzymes and Genes Involved in Aerobic Alkane Degradation

    Directory of Open Access Journals (Sweden)

    ZongzeShao

    2013-05-01

    Full Text Available Alkanes are major constituents of crude oil. They are also present at low concentrations in diverse non-contaminated because many living organisms produce them as chemo-attractants or as protecting agents against water loss. Alkane degradation is a widespread phenomenon in nature. The numerous microorganisms, both prokaryotic and eukaryotic, capable of utilizing alkanes as a carbon and energy source, have been isolated and characterized. This review summarizes the current knowledge of how bacteria metabolize alkanes aerobically, with a particular emphasis on the oxidation of long-chain alkanes, including factors that are responsible for chemotaxis to alkanes , transport across cell membrane of alkanes , the regulation of alkane degradation gene and initial oxidation.

  16. Gene duplications in prokaryotes can be associated with environmental adaptation

    Directory of Open Access Journals (Sweden)

    Lempicki Richard A

    2010-10-01

    Full Text Available Abstract Background Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes. Results Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis. Conclusions Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive

  17. Expression and contributions of the Kir2.1 inward-rectifier K+ channel to proliferation, migration and chemotaxis of microglia in unstimulated and anti-inflammatory states

    Directory of Open Access Journals (Sweden)

    Lyanne Schlichter

    2015-05-01

    Full Text Available When microglia respond to CNS damage, they can range from pro-inflammatory (classical, M1 to anti-inflammatory, alternative (M2 and acquired deactivation states. It is important to determine how microglial functions are affected by these activation states, and to identify molecules that regulate their behavior. Microglial proliferation and migration are crucial during development and following damage in the adult, and both functions are Ca2+-dependent. In many cell types, the membrane potential and driving force for Ca2+ influx are regulated by inward-rectifier K+ channels, including Kir2.1, which is prevalent in microglia. However, it is not known whether Kir2.1 expression and contributions are altered in anti-inflammatory states. We tested the hypothesis that Kir2.1 contributes to Ca2+ entry, proliferation and migration of rat microglia. Kir2.1 (KCNJ2 transcript expression, current amplitude, and proliferation were comparable in unstimulated microglia and following alternative activation (IL-4 stimulated and acquired deactivation (IL-10 stimulated. To examine functional roles of Kir2.1 in microglia, we first determined that ML133 was more effective than the commonly used blocker, Ba2+; i.e., ML133 was potent (IC50=3.5 M and voltage independent. Both blockers slightly increased proliferation in unstimulated or IL-4 (but not IL-10-stimulated microglia. Stimulation with IL-4 or IL-10 increased migration and ATP-induced chemotaxis, and blocking Kir2.1 greatly reduced both but ML133 was more effective. In all three activation states, blocking Kir2.1 with ML133 dramatically reduced Ca2+ influx through Ca2+-release-activated Ca2+ (CRAC channels. Thus, Kir2.1 channel activity is necessary for microglial Ca2+ signaling and migration under resting and anti-inflammatory states but the channel weakly inhibits proliferation.

  18. Loss of C-terminal α-helix decreased SDF-1α-mediated signaling and chemotaxis without influencing CXCR4 internalization

    Institute of Scientific and Technical Information of China (English)

    Shao-hui CAI; Yi TAN; Xian-da REN; Xiao-hong LI; Shao-xi CAI; Jun DU

    2004-01-01

    AIM: To investigate the possibility that a novel α-helix-defective mutant of stromal cell-derived factor-1α (SDF-1α) (SDF-1/54R) acts as an antagonist of CXC chemokine receptor 4 (CXCR4). METHODS: According to the genetic sequence of natural SDF- 1 α, a recombinant α-helix-defective mutant of SDF- 1 α was designed and some biologic characteristics of this mutant were demonstrated. The migration of Jurkat cells was assessed with chemotactic assay. ERK phosphorylation was analyzed by Western blot with a specific anti-phospho-ERK 1/2 antibody.Intracellular calcium influx was examined by flow cytometer with a calcium indicator dye Fluo-3AM. The CXCR4 on the cell surface was detected by flow cytometer with a PE conjoined anti-human CXCR4 antibody. RESULTS:Compared with native SDF-1α, SDF-1/54R displayed apparent decrease in chemotactic ability, ERK 1/2 activation,and intracellular calcium influx in Jurkat cells. However, the binding to CXCR4 and inducing CXCR4 internalization of SDF-1/54R did not change outstandingly. Moreover, a competitive inhibitory effect of SDF-1/54R on the migration of Jurkat cells induced by native SDF-1 α was confirmed. CONCLUSION: α-helix-defective mutant of SDF-1 α, SDF-1/54R that remained both the N-terminus and the central β-sheet region, decreased SDF-1 α-mediated signaling and chemotaxis but did not influence CXCR4 internalization, which suggested that SDF-1/54R might be developed as an anti-CHIV inhibitor with high biological potency and low side-effect.

  19. Cxcr3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allografts and mediate chemotaxis of T cells at sites of rejection.

    Science.gov (United States)

    Agostini, C; Calabrese, F; Rea, F; Facco, M; Tosoni, A; Loy, M; Binotto, G; Valente, M; Trentin, L; Semenzato, G

    2001-05-01

    The attraction of T lymphocytes into the pulmonary parenchyma represents an essential step in mechanisms ultimately leading to lung allograft rejection. In this study we evaluated whether IP-10 (CXCL10), a chemokine that is induced by interferon-gamma and stimulates the directional migration of activated T cells, plays a role in regulating the trafficking of effector T cells during lung allograft rejection episodes. Immunohistochemical examination showed that areas characterized by acute cellular rejection (grades 1 to 4) and active obliterative bronchiolitis (chronic rejection, Ca) were infiltrated by T cells expressing CXCR3, i.e., the specific receptor for CXCL10. In parallel, T cells accumulating in the bronchoalveolar lavage of lung transplant recipients with rejection episodes were CXCR3+ and exhibited a strong in vitro migratory capability in response to CXCL10. In lung biopsies, CXCL10 was abundantly expressed by graft-infiltrating macrophages and occasionally by epithelial cells. Alveolar macrophages expressed and secreted definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3+ T-cell line 300-19; the secretory capability of alveolar macrophages was up-regulated by preincubation with interferon-gamma. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the bronchoalveolar lavage in individuals with rejection episodes. These data indicate the role of the CXCR3/CXCL10 interactions in the recruitment of lymphocytes at sites of lung rejection and provide a rationale for the use of agents that block the CXCR3/CXCL10 axis in the treatment of lung allograft rejection. PMID:11337368

  20. Comparative gene-expression analysis of the dental follicle and periodontal ligament in humans.

    Directory of Open Access Journals (Sweden)

    Hyo-Seol Lee

    Full Text Available The human dental follicle partially differentiates into the periodontal ligament (PDL, but their biological functions are different. The gene-expression profiles of the dental follicle and PDL were compared using the cDNA microarray technique. Microarray analysis identified 490 genes with a twofold or greater difference in expression, 365 and 125 of which were more abundant in the dental follicle and PDL, respectively. The most strongly expressed genes in the dental follicle were those related to bone development and remodeling (EGFL6, MMP8, FRZB, and NELL1, apoptosis and chemotaxis (Nox4, CXCL13, and CCL2, and tooth and embryo development (WNT2, PAX3, FGF7, AMBN, AMTN, and SLC4A4, while in the PDL it was the tumor-suppressor gene WIF1. Genes related to bone development and remodeling (STMN2, IBSP, BMP8A, BGLAP, ACP5, OPN, BMP3, and TM7SF4 and wound healing (IL1, IL8, MMP3, and MMP9 were also more strongly expressed in the PDL than in the dental follicle. In selected genes, a comparison among cDNA microarray, real-time reverse-transcription polymerase chain reaction, and immunohistochemical staining confirmed similar relative gene expressions. The gene-expression profiles presented here identify candidate genes that may enable differentiation between the dental follicle and PDL.

  1. Screening New Drugs for Immunotoxic Potential: II. Assessment of the Effects of Selective and Nonselective COX-2 Inhibitors on Complement Activation, Superoxide Anion Production and Leukocyte Chemotaxis and Migration Through Endothelial Cells.

    Science.gov (United States)

    Furst, Sylvia M; Khan, K Nasir; Komocsar, Wendy J; Fan, Lian; Mennear, John

    2005-04-01

    Results from earlier experiments in our laboratories revealed that both selective and nonselective inhibitors of cyclooxygenase-2 possess little potential for decreasing in vitro phagocytosis by rat macrophages or canine neutrophils and no potential for decreasing in vivo phagocytosis by the intact murine immune system. We now report the results of studies to assess in vitro and ex vivo effects of the drugs on 1) canine complement activation, 2) generation of superoxide anion and hydrogen peroxide (oxidative burst) by canine neutrophils, and 3) leukocytic chemotaxis and transmigration through endothelial cell monolayers. In vitro concentrations of naproxen sodium, SC-236, SC-245, and SC-791 ranging from 0.1 to 10 muM were tested for their abilities to inhibit canine complement-mediated hemolysis of opsonized sheep erythrocytes and to block phorbol myristate acetate-induced oxidative burst in canine neutrophils. Both models responded to known inhibitory agents, leupeptin in the complement activation test and staurosporine in the superoxide anion assay. In contrast, tested nonsteroidal anti-inflammatory drugs produced only trivial changes in complement activation and superoxide anion production. Experiments on plasma and neutrophils isolated from dogs administered an experimental selective COX-2 inhibitor during a 28-day toxicology study revealed no evidence of drug-associated changes in complement activation or formation of superoxide anion. SC-791 reduced chemotaxis of canine leukocytes toward zymosan-activated dog plasma, but not toward leukotriene B(4). None of the other drugs tested significantly affected leukocytic chemotaxis. Ibuprofen, SC-245 and SC-791 but not SC-236, reduced transmigration of canine leukocytes through endothelial cell monolayers. Based on the results of these experiments and our earlier studies we have concluded that, although high (suprapharmacologic) concentrations of the drugs may induce in vitro evidence of apparent immunomodulation of

  2. Sphingomonas wittichii Strain RW1 Genome-Wide Gene Expression Shifts in Response to Dioxins and Clay.

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    Benli Chai

    Full Text Available Sphingomonas wittichii strain RW1 (RW1 is one of the few strains that can grow on dibenzo-p-dioxin (DD. We conducted a transcriptomic study of RW1 using RNA-Seq to outline transcriptional responses to DD, dibenzofuran (DF, and the smectite clay mineral saponite with succinate as carbon source. The ability to grow on DD is rare compared to growth on the chemically similar DF even though the same initial dioxygenase may be involved in oxidation of both substrates. Therefore, we hypothesized the reason for this lies beyond catabolic pathways and may concern genes involved in processes for cell-substrate interactions such as substrate recognition, transport, and detoxification. Compared to succinate (SUC as control carbon source, DF caused over 240 protein-coding genes to be differentially expressed, whereas more than 300 were differentially expressed with DD. Stress response genes were up-regulated in response to both DD and DF. This effect was stronger with DD than DF, suggesting a higher toxicity of DD compared to DF. Both DD and DF caused changes in expression of genes involved in active cross-membrane transport such as TonB-dependent receptor proteins, but the patterns of change differed between the two substrates. Multiple transcription factor genes also displayed expression patterns distinct to DD and DF growth. DD and DF induced the catechol ortho- and the salicylate/gentisate pathways, respectively. Both DD and DF induced the shared down-stream aliphatic intermediate compound pathway. Clay caused category-wide down-regulation of genes for cell motility and chemotaxis, particularly those involved in the synthesis, assembly and functioning of flagella. This is an environmentally important finding because clay is a major component of soil microbes' microenvironment influencing local chemistry and may serve as a geosorbent for toxic pollutants. Similar to clay, DD and DF also affected expression of genes involved in motility and chemotaxis.

  3. Sphingomonas wittichii Strain RW1 Genome-Wide Gene Expression Shifts in Response to Dioxins and Clay

    Science.gov (United States)

    Tsoi, Tamara V.; Iwai, Shoko; Liu, Cun; Fish, Jordan A.; Gu, Cheng; Johnson, Timothy A.; Zylstra, Gerben; Teppen, Brian J.; Li, Hui; Hashsham, Syed A.; Boyd, Stephen A.; Cole, James R.; Tiedje, James M.

    2016-01-01

    Sphingomonas wittichii strain RW1 (RW1) is one of the few strains that can grow on dibenzo-p-dioxin (DD). We conducted a transcriptomic study of RW1 using RNA-Seq to outline transcriptional responses to DD, dibenzofuran (DF), and the smectite clay mineral saponite with succinate as carbon source. The ability to grow on DD is rare compared to growth on the chemically similar DF even though the same initial dioxygenase may be involved in oxidation of both substrates. Therefore, we hypothesized the reason for this lies beyond catabolic pathways and may concern genes involved in processes for cell-substrate interactions such as substrate recognition, transport, and detoxification. Compared to succinate (SUC) as control carbon source, DF caused over 240 protein-coding genes to be differentially expressed, whereas more than 300 were differentially expressed with DD. Stress response genes were up-regulated in response to both DD and DF. This effect was stronger with DD than DF, suggesting a higher toxicity of DD compared to DF. Both DD and DF caused changes in expression of genes involved in active cross-membrane transport such as TonB-dependent receptor proteins, but the patterns of change differed between the two substrates. Multiple transcription factor genes also displayed expression patterns distinct to DD and DF growth. DD and DF induced the catechol ortho- and the salicylate/gentisate pathways, respectively. Both DD and DF induced the shared down-stream aliphatic intermediate compound pathway. Clay caused category-wide down-regulation of genes for cell motility and chemotaxis, particularly those involved in the synthesis, assembly and functioning of flagella. This is an environmentally important finding because clay is a major component of soil microbes’ microenvironment influencing local chemistry and may serve as a geosorbent for toxic pollutants. Similar to clay, DD and DF also affected expression of genes involved in motility and chemotaxis. PMID:27309357

  4. Identification of genes responsive to solar simulated UV radiation in human monocyte-derived dendritic cells.

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    Hortensia de la Fuente

    Full Text Available Ultraviolet (UV irradiation has profound effects on the skin and the systemic immune system. Several effects of UV radiation on Dendritic cells (DCs functions have been described. However, gene expression changes induced by UV radiation in DCs have not been addressed before. In this report, we irradiated human monocyte-derived DCs with solar-simulated UVA/UVB and analyzed regulated genes on human whole genome arrays. Results were validated by RT-PCR and further analyzed by Gene Set Enrichment Analysis (GSEA. Solar-simulated UV radiation up-regulated expression of genes involved in cellular stress and inflammation, and down-regulated genes involved in chemotaxis, vesicular transport and RNA processing. Twenty four genes were selected for comparison by RT-PCR with similarly treated human primary keratinocytes and human melanocytes. Several genes involved in the regulation of the immune response were differentially regulated in UVA/UVB irradiated human monocyte-derived DCs, such as protein tyrosine phosphatase, receptor type E (PTPRE, thrombospondin-1 (THBS1, inducible costimulator ligand (ICOSL, galectins, Src-like adapter protein (SLA, IL-10 and CCR7. These results indicate that UV-exposure triggers the regulation of a complex gene repertoire involved in human-DC-mediated immune responses.

  5. The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

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    Hai-Shu Lin

    2013-11-01

    Full Text Available MS-275 (entinostat and SAHA (vorinostat, two histone deacetylase (HDAC inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA. To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α  MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1, an endogenous suppressor of p38α  in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation of p38α  was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2, monocyte chemotactic protein-2 (MCP-2 and macrophage migration inhibitory factor (MIF in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.

  6. Chemotaxis of Pseudomonas to furans

    Science.gov (United States)

    Background: Furfural (2-furaldehyde) is a furan compound formed by dehydration of pentose sugars. Furan molecules occur naturally in the environment and are also used industrially as solvents and chemical precursors. Although furan aldehydes are microbial inhibitors, a number of microbes can utilize...

  7. Gene expression

    International Nuclear Information System (INIS)

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn2+ or Cd2+. We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  8. In Vitro Global Gene Expression Analyses Support the Ethnopharmacological Use of Achyranthes aspera

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    Pochi R. Subbarayan

    2013-01-01

    Full Text Available Achyranthes aspera (family Amaranthaceae is known for its anticancer properties. We have systematically validated the in vitro and in vivo anticancer properties of this plant. However, we do not know its mode of action. Global gene expression analyses may help decipher its mode of action. In the absence of identified active molecules, we believe this is the best approach to discover the mode of action of natural products with known medicinal properties. We exposed human pancreatic cancer cell line MiaPaCa-2 (CRL-1420 to 34 μg/mL of LE for 24, 48, and 72 hours. Gene expression analyses were performed using whole human genome microarrays (Agilent Technologies, USA. In our analyses, 82 (54/28 genes passed the quality control parameter, set at FDR ≤ 0.01 and FC of ≥±2. LE predominantly affected pathways of immune response, metabolism, development, gene expression regulation, cell adhesion, cystic fibrosis transmembrane conductance regulation (CFTR, and chemotaxis (MetaCore tool (Thomson Reuters, NY. Disease biomarker enrichment analysis identified LE regulated genes involved in Vasculitis—inflammation of blood vessels. Arthritis and pancreatitis are two of many etiologies for vasculitis. The outcome of disease network analysis supports the medicinal use of A. aspera, viz, to stop bleeding, as a cure for pancreatic cancer, as an antiarthritic medication, and so forth.

  9. Transcriptional analysis of temporal gene expression in germinating Clostridium difficile 630 endospores.

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    Marcin Dembek

    Full Text Available Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01. A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth.

  10. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  11. Gene loss and horizontal gene transfer contributed to the genome evolution of the extreme acidophile Ferrovum

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    Sophie Roxana Ullrich

    2016-05-01

    Full Text Available Acid mine drainage (AMD, associated with active and abandoned mining sites, is a habitat for acidophilic microorganisms that gain energy from the oxidation of reduced sulfur compounds and ferrous iron and that thrive at pH below 4. Members of the recently proposed genus Ferrovum are the first acidophilic iron oxidizers to be described within the Betaproteobacteria. Although they have been detected as typical community members in AMD habitats worldwide, knowledge of their phylogenetic and metabolic diversity is scarce. Genomics approaches appear to be most promising in addressing this lacuna since isolation and cultivation of Ferrovum has proven to be extremely difficult and has so far only been successful for the designated type strain Ferrovum myxofaciens P3G. In this study, the genomes of two novel strains of Ferrovum (PN-J185 and Z-31 derived from water samples of a mine water treatment plant were sequenced. These genomes were compared with those of Ferrovum sp. JA12 that also originated from the mine water treatment plant, and of the type strain (P3G. Phylogenomic scrutiny suggests that the four strains represent three Ferrovum species that cluster in two groups (1 and 2. Comprehensive analysis of their predicted metabolic pathways revealed that these groups harbor characteristic metabolic profiles, notably with respect to motility, chemotaxis, nitrogen metabolism, biofilm formation and their potential strategies to cope with the acidic environment. For example, while the F. myxofaciens strains (group 1 appear to be motile and diazotrophic, the non-motile group 2 strains have the predicted potential to use a greater variety of fixed nitrogen sources. Furthermore, analysis of their genome synteny provides first insights into their genome evolution, suggesting that horizontal gene transfer and genome reduction in the group 2 strains by loss of genes encoding complete metabolic pathways or physiological features contributed to the observed

  12. Gene therapy.

    OpenAIRE

    Mota Biosca, Anna

    1992-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases.

  13. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela; Goedegebuur, Frits; Van Solingen, Pieter; Ward, Michael

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  14. Time-dependent gene expression analysis after mouse skeletal muscle contusion

    Institute of Scientific and Technical Information of China (English)

    Weihua Xiao; Yu Liu; Beibei Luo; Linlin Zhao; Xiaoguang Liu; Zhigang Zeng; Peijie Chen

    2016-01-01

    Background: Though the mechanisms of skeletal muscle regeneration are deeply understood, those involved in muscle contusion, one of the most common muscle injuries in sports medicine clinics, are not. The objective of this study is to explore the mechanisms involved in muscle regeneration after contusion injury. Methods: In this study, a total of 72 mice were used. Eight of them were randomly chosen for the control group, while the rest were subjected to muscle contusion. Subsequently, their gastrocnemius muscles were harvested at different time points. The changes in muscle morphology were assessed by hematoxylin and eosin (HE) stain. In addition, the gene expression was analyzed by real-time polymerase chain reaction. Results: The data showed that the expression of many genes, i.e., specific markers of immune cells and satellite cells, regulatory factors for muscle regeneration, cytokines, and chemokines, increased in the early stages of recovery, especially in the first 3 days. Furthermore, there were strict rules in the expression of these genes. However, almost all the genes returned to normal at 14 days post-injury. Conclusion: The sequence of immune cells invaded after muscle contusion was neutrophils, M1 macrophages and M2 macrophages. Some CC (CCL2, CCL3, and CCL4) and CXC (CXCL10) chemokines may be involved in the chemotaxis of these immune cells. HGF may be the primary factor to activate the satellite cells after muscle contusion. Moreover, 2 weeks are needed to recover when acute contusion happens as used in this study.

  15. Chemotaxis and degradation of organophosphate compound by a novel moderately thermo-halo tolerant Pseudomonas sp. strain BUR11: evidence for possible existence of two pathways for degradation

    OpenAIRE

    Pailan, Santanu; Saha, Pradipta

    2015-01-01

    An organophosphate (OP) degrading chemotactic bacterial strain BUR11 isolated from an agricultural field was identified as a member of Pseudomonas genus on the basis of its 16S rRNA gene sequence. The strain could utilize parathion, chlorpyrifos and their major hydrolytic intermediates as sole source of carbon for its growth and exhibited positive chemotactic response towards most of them. Optimum concentration of parathion for its growth was recorded to be 200 ppm and 62% of which was degrad...

  16. ELMO1 Is Upregulated in AML CD34+ Stem/Progenitor Cells, Mediates Chemotaxis and Predicts Poor Prognosis in Normal Karyotype AML

    OpenAIRE

    Capala, Marta E.; Vellenga, Edo; Schuringa, Jan Jacob

    2014-01-01

    Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML) cells (n = 46), their more differentiated CD34− leukemic progeny, and normal CD34+ bone marrow cells (n = 31) and focused on differentially expressed genes in...

  17. [Language gene].

    Science.gov (United States)

    Takahashi, Hiroshi

    2006-11-01

    The human capacity for acquiring speech and language must derive, at least in part, from the genome. Recent advance in the field of molecular genetics finally discovered 'Language Gene'. Disruption of FOXP2 gene, the firstly identified 'language gene' causes severe speech and language disorder. To elucidate the anatomical basis of language processing in the brain, we examined the expression pattern of FOXP2/Foxp2 genes in the monkey and rat brains through development. We found the preferential expression of FOXP2/Foxp2 in the striosomal compartment of the developing striatum. Thus, we suggest the striatum, particularly striosomal system may participate in neural information processing for language and speech. Our suggestion is consistent with the declarative/ procedural model of language proposed by Ullman (1997, 2001), which the procedural memory-dependent mental grammar is rooted in the basal ganglia and the frontal cortex, and the declarative memory-dependent mental lexicon is rooted in the temporal lobe. PMID:17432197

  18. Gene Silencing

    Czech Academy of Sciences Publication Activity Database

    Kertbundit, Sunee; Juříček, Miloslav; Hall, T.C.

    Dordrecht : Springer, 2010 - (Jain, S.; Brar, D.), s. 631-652 ISBN 978-90-481-2966-9 Institutional research plan: CEZ:AV0Z50380511 Keywords : Gene Silencing * RISC complex Subject RIV: EB - Genetics ; Molecular Biology

  19. A large-scale screen reveals genes that mediate electrotaxis in Dictyostelium discoideum.

    Science.gov (United States)

    Gao, Runchi; Zhao, Siwei; Jiang, Xupin; Sun, Yaohui; Zhao, Sanjun; Gao, Jing; Borleis, Jane; Willard, Stacey; Tang, Ming; Cai, Huaqing; Kamimura, Yoichiro; Huang, Yuesheng; Jiang, Jianxin; Huang, Zunxi; Mogilner, Alex; Pan, Tingrui; Devreotes, Peter N; Zhao, Min

    2015-05-26

    Directional cell migration in an electric field, a phenomenon called galvanotaxis or electrotaxis, occurs in many types of cells, and may play an important role in wound healing and development. Small extracellular electric fields can guide the migration of amoeboid cells, and we established a large-scale screening approach to search for mutants with electrotaxis phenotypes from a collection of 563 Dictyostelium discoideum strains with morphological defects. We identified 28 strains that were defective in electrotaxis and 10 strains with a slightly higher directional response. Using plasmid rescue followed by gene disruption, we identified some of the mutated genes, including some previously implicated in chemotaxis. Among these, we studied PiaA, which encodes a critical component of TORC2, a kinase protein complex that transduces changes in motility by activating the kinase PKB (also known as Akt). Furthermore, we found that electrotaxis was decreased in mutants lacking gefA, rasC, rip3, lst8, or pkbR1, genes that encode other components of the TORC2-PKB pathway. Thus, we have developed a high-throughput screening technique that will be a useful tool to elucidate the molecular mechanisms of electrotaxis. PMID:26012633

  20. Differential gene expression by integrin β7+ and β7- memory T helper cells

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    Yang Yee

    2004-07-01

    Full Text Available Abstract Background The cell adhesion molecule integrin α4β7 helps direct the migration of blood lymphocytes to the intestine and associated lymphoid tissues. We hypothesized that β7+ and β7- blood memory T helper cells differ in their expression of genes that play a role in the adhesion or migration of T cells. Results RNA was prepared from β7+ and β7- CD4+ CD45RA- blood T cells from nine normal human subjects and analyzed using oligonucleotide microarrays. Of 21357 genes represented on the arrays, 16 were more highly expressed in β7+ cells and 18 were more highly expressed in β7- cells (≥1.5 fold difference and adjusted P + memory/effector T cells than on β7- cells. Conclusions Memory/effector T cells that express integrin β7 have a distinct pattern of expression of a set of gene transcripts. Several of these molecules can affect cell adhesion or chemotaxis and are therefore likely to modulate the complex multistep process that regulates trafficking of CD4+ memory T cell subsets with different homing behaviors.

  1. Sequential waves of gene expression in patients with clinically defined dengue illnesses reveal subtle disease phases and predict disease severity.

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    Peifang Sun

    Full Text Available BACKGROUND: Dengue virus (DENV infection can range in severity from mild dengue fever (DF to severe dengue hemorrhagic fever (DHF or dengue shock syndrome (DSS. Changes in host gene expression, temporally through the progression of DENV infection, especially during the early days, remains poorly characterized. Early diagnostic markers for DHF are also lacking. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated host gene expression in a cohort of DENV-infected subjects clinically diagnosed as DF (n = 51 and DHF (n = 13 from Maracay, Venezuela. Blood specimens were collected daily from these subjects from enrollment to early defervescence and at one convalescent time-point. Using convalescent expression levels as baseline, two distinct groups of genes were identified: the "early" group, which included genes associated with innate immunity, type I interferon, cytokine-mediated signaling, chemotaxis, and complement activity peaked at day 0-1 and declined on day 3-4; the second "late" group, comprised of genes associated with cell cycle, emerged from day 4 and peaked at day 5-6. The up-regulation of innate immune response genes coincided with the down-regulation of genes associated with viral replication during day 0-3. Furthermore, DHF patients had lower expression of genes associated with antigen processing and presentation, MHC class II receptor, NK and T cell activities, compared to that of DF patients. These results suggested that the innate and adaptive immunity during the early days of the disease are vital in suppressing DENV replication and in affecting outcome of disease severity. Gene signatures of DHF were identified as early as day 1. CONCLUSIONS/SIGNIFICANCE: Our study reveals a broad and dynamic picture of host responses in DENV infected subjects. Host response to DENV infection can now be understood as two distinct phases with unique transcriptional markers. The DHF signatures identified during day 1-3 may have

  2. Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: insights into the genes required for mouse infectivity.

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    Tao Lin

    Full Text Available The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by exceedingly low transformation rates in low-passage, infectious organisms. Using the infectious, moderately transformable B. burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1 transposon vector pGKT, we have constructed a defined transposon library for the efficient genome-wide investigation of genes required for wild-type pathogenesis, in vitro growth, physiology, morphology, and plasmid replication. To facilitate analysis, the insertion sites of 4,479 transposon mutants were determined by sequencing. The transposon insertions were widely distributed across the entire B. burgdorferi genome, with an average of 2.68 unique insertion sites per kb DNA. The 10 linear plasmids and 9 circular plasmids had insertions in 33 to 100 percent of their predicted genes. In contrast, only 35% of genes in the 910 kb linear chromosome had incapacitating insertions; therefore, the remaining 601 chromosomal genes may represent essential gene candidates. In initial signature-tagged mutagenesis (STM analyses, 434 mutants were examined at multiple tissue sites for infectivity in mice using a semi-quantitative, Luminex-based DNA detection method. Examples of genes found to be important in mouse infectivity included those involved in motility, chemotaxis, the phosphoenolpyruvate phosphotransferase system, and other transporters, as well as putative plasmid maintenance genes. Availability of this ordered STM library and a high-throughput screening method is expected to lead to efficient assessment of the roles of B. burgdorferi genes in the infectious cycle and pathogenesis of Lyme disease.

  3. Differential gene expression profile associated with the abnormality of bone marrow mesenchymal stem cells in aplastic anemia.

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    Jianping Li

    Full Text Available Aplastic anemia (AA is generally considered as an immune-mediated bone marrow failure syndrome with defective hematopoietic stem cells (HSCs and marrow microenvironment. Previous studies have demonstrated the defective HSCs and aberrant T cellular-immunity in AA using a microarray approach. However, little is known about the overall specialty of bone marrow mesenchymal stem cells (BM-MSCs. In the present study, we comprehensively compared the biological features and gene expression profile of BM-MSCs between AA patients and healthy volunteers. In comparison with healthy controls, BM-MSCs from AA patients showed aberrant morphology, decreased proliferation and clonogenic potential and increased apoptosis. BM-MSCs from AA patients were susceptible to be induced to differentiate into adipocytes but more difficult to differentiate into osteoblasts. Consistent with abnormal biological features, a large number of genes implicated in cell cycle, cell division, proliferation, chemotaxis and hematopoietic cell lineage showed markedly decreased expression in BM-MSCs from AA patients. Conversely, more related genes with apoptosis, adipogenesis and immune response showed increased expression in BM-MSCs from AA patients. The gene expression profile of BM-MSCs further confirmed the abnormal biological properties and provided significant evidence for the possible mechanism of the destruction of the bone marrow microenvironment in AA.

  4. The molecular identities of the Caenorhabditis elegans intraflagellar transport genes dyf-6, daf-10 and osm-1.

    Science.gov (United States)

    Bell, Leslie R; Stone, Steven; Yochem, John; Shaw, Jocelyn E; Herman, Robert K

    2006-07-01

    The Caenorhabditis elegans genes dyf-6, daf-10, and osm-1 are among the set of genes that affect chemotaxis and the ability of certain sensory neurons to take up fluorescent dyes from the environment. Some genes in this category are known to be required for intraflagellar transport (IFT), which is the bidirectional movement of raft-like particles along the axonemes of cilia and flagella. The cloning of dyf-6, daf-10, and osm-1 are described here. The daf-10 and osm-1 gene products resemble each other and contain WD and WAA repeats. DYF-6, the product of a complex locus, lacks known motifs, but orthologs are present in flies and mammals. Phenotypic analysis of dyf-6 mutants expressing an OSM-6::GFP reporter indicates that the cilia of the amphid and phasmid dendritic endings are foreshortened. Consistent with genetic mosaic analysis, which indicates that dyf-6 functions in neurons of the amphid sensilla, DYF-6::GFP is expressed in amphid and phasmid neurons. Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT. In addition, IFT can be observed in dauer larvae. PMID:16648645

  5. Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

    Science.gov (United States)

    Yamaguchi, T.; Chattopadhyay, N.; Kifor, O.; Butters, R. R. Jr; Sugimoto, T.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

    1998-01-01

    The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

  6. PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.

    Science.gov (United States)

    Jeong, Jinseon; Kim, Young-Jun; Yoon, Sun Young; Kim, Yong-Jae; Kim, Joo Heon; Sohn, Ki-Young; Kim, Heung-Jae; Han, Yong-Hae; Chong, Saeho; Kim, Jae Wha

    2016-01-01

    Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium. PMID:27010397

  7. Genes and Psoriasis

    Science.gov (United States)

    ... Diet Tips" to find out more! Email * Zipcode Genes and Psoriasis Genes hold the key to understanding ... is responsible for causing psoriatic disease. How do genes work? Genes control everything from height to eye ...

  8. Genes and Hearing Loss

    Science.gov (United States)

    ... Meeting Calendar Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  9. Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

    Science.gov (United States)

    Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

    2011-09-15

    Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

  10. Shotgun Metagenomic Sequencing Reveals Functional Genes and Microbiome Associated with Bovine Digital Dermatitis.

    Directory of Open Access Journals (Sweden)

    Martin Zinicola

    Full Text Available Metagenomic methods amplifying 16S ribosomal RNA genes have been used to describe the microbial diversity of healthy skin and lesion stages of bovine digital dermatitis (DD and to detect critical pathogens involved with disease pathogenesis. In this study, we characterized the microbiome and for the first time, the composition of functional genes of healthy skin (HS, active (ADD and inactive (IDD lesion stages using a whole-genome shotgun approach. Metagenomic sequences were annotated using MG-RAST pipeline. Six phyla were identified as the most abundant. Firmicutes and Actinobacteria were the predominant bacterial phyla in the microbiome of HS, while Spirochetes, Bacteroidetes and Proteobacteria were highly abundant in ADD and IDD. T. denticola-like, T. vincentii-like and T. phagedenis-like constituted the most abundant species in ADD and IDD. Recruitment plots comparing sequences from HS, ADD and IDD samples to the genomes of specific Treponema spp., supported the presence of T. denticola and T. vincentii in ADD and IDD. Comparison of the functional composition of HS to ADD and IDD identified a significant difference in genes associated with motility/chemotaxis and iron acquisition/metabolism. We also provide evidence that the microbiome of ADD and IDD compared to that of HS had significantly higher abundance of genes associated with resistance to copper and zinc, which are commonly used in footbaths to prevent and control DD. In conclusion, the results from this study provide new insights into the HS, ADD and IDD microbiomes, improve our understanding of the disease pathogenesis and generate unprecedented knowledge regarding the functional genetic composition of the digital dermatitis microbiome.

  11. Gene gymnastics

    Science.gov (United States)

    Vijayachandran, Lakshmi S; Thimiri Govinda Raj, Deepak B; Edelweiss, Evelina; Gupta, Kapil; Maier, Josef; Gordeliy, Valentin; Fitzgerald, Daniel J; Berger, Imre

    2013-01-01

    Most essential activities in eukaryotic cells are catalyzed by large multiprotein assemblies containing up to ten or more interlocking subunits. The vast majority of these protein complexes are not easily accessible for high resolution studies aimed at unlocking their mechanisms, due to their low cellular abundance and high heterogeneity. Recombinant overproduction can resolve this bottleneck and baculovirus expression vector systems (BEVS) have emerged as particularly powerful tools for the provision of eukaryotic multiprotein complexes in high quality and quantity. Recently, synthetic biology approaches have begun to make their mark in improving existing BEVS reagents by de novo design of streamlined transfer plasmids and by engineering the baculovirus genome. Here we present OmniBac, comprising new custom designed reagents that further facilitate the integration of heterologous genes into the baculovirus genome for multiprotein expression. Based on comparative genome analysis and data mining, we herein present a blueprint to custom design and engineer the entire baculovirus genome for optimized production properties using a bottom-up synthetic biology approach. PMID:23328086

  12. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  13. Optimal chemotaxis in animal cell intermittent migration

    CERN Document Server

    Romanczuk, Pawel

    2015-01-01

    Animal cells can sense chemical gradients without moving, and are faced with the challenge of migrating towards a target despite noisy information on the target position. Here we discuss optimal search strategies for a chaser that moves by switching between two phases of motion ("run" and "tumble"), reorienting itself towards the target during tumble phases, and performing a persistent random walk during run phases. We show that the chaser average run time can be adjusted to minimize the target catching time or the spatial dispersion of the chasers. We obtain analytical results for the catching time and for the spatial dispersion in the limits of small and large ratios of run time to tumble time, and scaling laws for the optimal run times. Our findings have implications for optimal chemotactic strategies in animal cell migration.

  14. Mast cell chemotaxis - chemoattractants and signaling pathways

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2012-01-01

    Roč. 3, May (2012), s. 119. ISSN 1664-3224 R&D Projects: GA MŠk LD12073; GA ČR GA301/09/1826; GA ČR GAP302/10/1759 Grant ostatní: ECST(XE) BM1007; AV ČR(CZ) MC200520901 Institutional support: RVO:68378050 Keywords : mast cell * IgE receptor * plasma membrane Subject RIV: EB - Genetics ; Molecular Biology

  15. Collective chemotaxis through noisy multicellular gradient sensing

    CERN Document Server

    Varennes, Julien; Mugler, Andrew

    2016-01-01

    Collective cell migration in response to a chemical cue occurs in many biological processes such as morphogenesis and cancer metastasis. Clusters of migratory cells in these systems are capable of responding to gradients of less than 1% difference in chemical concentration across a cell length. Multicellular systems are extremely sensitive to their environment and while the limits to multicellular sensing are becoming known, how this information leads to coherent migration remains poorly understood. We develop a computational model of multicellular sensing and migration in which groups of cells collectively measure noisy chemical gradients. The output of the sensing process is coupled to individual cells polarization to model migratory behavior. Through the use of numerical simulations, we find that larger clusters of cells detect the gradient direction with higher precision and thus achieve stronger polarization bias, but larger clusters also induce more drag on collective motion. The trade-off between these...

  16. Information and Metabolism in Bacterial Chemotaxis

    OpenAIRE

    Gennaro Auletta

    2013-01-01

    One of the most important issues in theoretical biology is to understand how control mechanisms are deployed by organisms to maintain their homeostasis and ensure their survival. A crucial issue is how organisms deal with environmental information in a way that ensures appropriate exchanges with the environment — even in the most basic of life forms (namely, bacteria). In this paper, I present an information theoretic formulation of how Escherichia coli responds to environmental inf...

  17. Chemotaxis in the archaebacterium Methanococcus voltae.

    OpenAIRE

    Sment, K A; Konisky, J

    1989-01-01

    The archaebacterium Methanococcus voltae, was shown to be chemotactic. Acetate, isoleucine, and leucine were identified as attractants; whereas histidine was not an attractant. A motile, generally nonchemotactic mutant was isolated.

  18. Travelling Waves in Hyperbolic Chemotaxis Equations

    KAUST Repository

    Xue, Chuan

    2010-10-16

    Mathematical models of bacterial populations are often written as systems of partial differential equations for the densities of bacteria and concentrations of extracellular (signal) chemicals. This approach has been employed since the seminal work of Keller and Segel in the 1970s (Keller and Segel, J. Theor. Biol. 30:235-248, 1971). The system has been shown to permit travelling wave solutions which correspond to travelling band formation in bacterial colonies, yet only under specific criteria, such as a singularity in the chemotactic sensitivity function as the signal approaches zero. Such a singularity generates infinite macroscopic velocities which are biologically unrealistic. In this paper, we formulate a model that takes into consideration relevant details of the intracellular processes while avoiding the singularity in the chemotactic sensitivity. We prove the global existence of solutions and then show the existence of travelling wave solutions both numerically and analytically. © 2010 Society for Mathematical Biology.

  19. Recombinant DNA repair genes

    International Nuclear Information System (INIS)

    We have developed a gene transfer system with Chinese hamster ovary (CHO) cells to identify, characterize, and potentially isolate functionally homologous human or CHO genes regulating repair initiation

  20. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  1. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k+) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k+ gene expression where the H S V-1 t k+ gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([18 F]F H P G; [18 F]-A C V), and pyrimidine- ([123/131 I]I V R F U; [124/131I]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [123/131I]I V R F U imaging with the H S V-1 t k+ reporter gene will be presented

  2. Identifying Gene Interaction Enrichment for Gene Expression Data

    OpenAIRE

    Jigang Zhang; Jian Li; Hong-Wen Deng

    2009-01-01

    Gene set analysis allows the inclusion of knowledge from established gene sets, such as gene pathways, and potentially improves the power of detecting differentially expressed genes. However, conventional methods of gene set analysis focus on gene marginal effects in a gene set, and ignore gene interactions which may contribute to complex human diseases. In this study, we propose a method of gene interaction enrichment analysis, which incorporates knowledge of predefined gene sets (e.g. gene ...

  3. Pristane-induced arthritis loci interact with the Slc11a1 gene to determine susceptibility in mice selected for high inflammation.

    Science.gov (United States)

    De Franco, Marcelo; Peters, Luciana C; Correa, Mara A; Galvan, Antonella; Canhamero, Tatiane; Borrego, Andrea; Jensen, José R; Gonçalves, Jussara; Cabrera, Wafa H K; Starobinas, Nancy; Ribeiro, Orlando G; Dragani, Tommaso A; Dragani, Tommaso; Ibañez, Olga M

    2014-01-01

    AIRmax (maximal inflammation) and AIRmin (minimal inflammation) mice show distinct susceptibilities to pristane-induced arthritis (PIA). The Slc11a1 gene, which regulates macrophage and neutrophil activity, is involved in this infirmity. AIRmax (SS) mice homozygous for the non-functional Slc11a1 S (gly169asp) allele obtained by genotype-assisted crosses from AIRmax and AIRmin mice are more susceptible than mice homozygous for the Slc11a1 resistant (R) allele. The present work sought to identify the quantitative trait loci (QTL) regulating PIA and to examine the interactions of these QTL with Slc11a1 alleles in modulating PIA. Mice were given two ip injections of 0.5 mL pristane at 60 day intervals, and the incidence and severity of PIA was scored up to 160 days. Genome-wide linkage studies were performed to search for arthritis QTL in an F2 (AIRmax × AIRmin, n = 290) population. Significant arthritis QTL (LODscore>4) were detected on chromosomes 5 and 8, and suggestive QTL on chromosomes 7, 17 and 19. Global gene expression analyses performed on Affymetrix mouse 1.0 ST bioarrays (27k genes) using RNA from arthritic or control mice paws showed 419 differentially expressed genes between AIRmax and AIRmin mice and demonstrated significantly (P<0.001) over-represented genes related to inflammatory responses and chemotaxis. Up-regulation of the chemokine genes Cxcl1, Cxcl9, Cxcl5, Cxcl13 on chromosome 5 was higher in AIRmax(SS) than in the other lines. Macrophage scavenger receptor 1 and hemeoxigenase (decycling) 1 genes on chromosome 8 were also expressed at higher levels in AIRmax(SS) mice. Our results show that the gene expression profiles of the two arthritis QTL (on chromosomes 5 and 8) correlate with Slc11a1 alleles, resulting in enhanced AIRmax(SS) mice susceptibility to PIA. PMID:24505471

  4. Dendritic cells transduced with Rsf-1/HBXAP gene generate specific cytotoxic T lymphocytes against ovarian cancer in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Li [Department of Gynecology Oncology, Shan Dong Tumor Hospital, Jinan, Shandong (China); Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong (China); Kong, Beihua, E-mail: kongbeihua@sdu.edu.cn [Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong (China); Sheng, Xiugui [Department of Gynecology Oncology, Shan Dong Tumor Hospital, Jinan, Shandong (China); Sheu, Jim Jinn-Chyuan [Human Genetic Center, China Medical University Hospital and Graduate Institute of Chinese Medical Science, China Medical University, Taichung City, Taiwan (China); Shih, Ie-Ming [Departments of Pathology, Oncology, and Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21231 (United States)

    2010-04-09

    Recently, some studies have indicated that Rsf-1/HBXAP plays a role in chromatin remodeling and transcriptional regulation that may contribute to tumorigenesis in ovarian cancer. The present study demonstrates that using dendritic cells (DCs) from human cord blood CD34{sup +} cells transduced with Rsf-1/HBXAP DNA plasmids by nucleofection generate specific cytotoxic T lymphocytes (CTL) against ovarian cancer in vitro. After transfection, DCs were analyzed for Rsf-1/HBXAP mRNA expression by RT-PCR and protein expression by Western blot. Then the DC phenotypes, T-cell stimulatory capacity, endocytic activity and migration capacity were explored by flow cytometry analysis, allogeneic mixed lymphocyte reaction, endocytosis and transwell chemotaxis assay, respectively. After transfection, Rsf-1/HBXAP expression was detected at mRNA and protein levels. Allogeneic T-cell proliferation induced by transfected DCs was obviously higher than non-transfected DCs, but the endocytosis capacity and migratory ability were not different. Rsf-1/HBXAP gene-transduced DCs could induce antigen-specific CTL and generate a very potent cytotoxicity to OVCAR3 cells. These data suggest that Rsf-1/HBXAP gene-transduced DCs may be a potential adjuvant immunotherapy for ovarian cancer in clinical applications.

  5. Dendritic cells transduced with Rsf-1/HBXAP gene generate specific cytotoxic T lymphocytes against ovarian cancer in vitro

    International Nuclear Information System (INIS)

    Recently, some studies have indicated that Rsf-1/HBXAP plays a role in chromatin remodeling and transcriptional regulation that may contribute to tumorigenesis in ovarian cancer. The present study demonstrates that using dendritic cells (DCs) from human cord blood CD34+ cells transduced with Rsf-1/HBXAP DNA plasmids by nucleofection generate specific cytotoxic T lymphocytes (CTL) against ovarian cancer in vitro. After transfection, DCs were analyzed for Rsf-1/HBXAP mRNA expression by RT-PCR and protein expression by Western blot. Then the DC phenotypes, T-cell stimulatory capacity, endocytic activity and migration capacity were explored by flow cytometry analysis, allogeneic mixed lymphocyte reaction, endocytosis and transwell chemotaxis assay, respectively. After transfection, Rsf-1/HBXAP expression was detected at mRNA and protein levels. Allogeneic T-cell proliferation induced by transfected DCs was obviously higher than non-transfected DCs, but the endocytosis capacity and migratory ability were not different. Rsf-1/HBXAP gene-transduced DCs could induce antigen-specific CTL and generate a very potent cytotoxicity to OVCAR3 cells. These data suggest that Rsf-1/HBXAP gene-transduced DCs may be a potential adjuvant immunotherapy for ovarian cancer in clinical applications.

  6. Autism and Genes

    Science.gov (United States)

    National Institutes of Health, 2005

    2005-01-01

    This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

  7. Principles of gene therapy

    Directory of Open Access Journals (Sweden)

    Mammen Biju

    2007-01-01

    Full Text Available Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics and future percepts and the technical and ethical issues of using gene therapy.

  8. Transcriptome profiling of a Sinorhizobium meliloti fadD mutant reveals the role of rhizobactin 1021 biosynthesis and regulation genes in the control of swarming

    Directory of Open Access Journals (Sweden)

    Olivares José

    2010-03-01

    Full Text Available Abstract Background Swarming is a multicellular phenomenom characterized by the coordinated and rapid movement of bacteria across semisolid surfaces. In Sinorhizobium meliloti this type of motility has been described in a fadD mutant. To gain insights into the mechanisms underlying the process of swarming in rhizobia, we compared the transcriptome of a S. meliloti fadD mutant grown under swarming inducing conditions (semisolid medium to those of cells grown under non-swarming conditions (broth and solid medium. Results More than a thousand genes were identified as differentially expressed in response to growth on agar surfaces including genes for several metabolic activities, iron uptake, chemotaxis, motility and stress-related genes. Under swarming-specific conditions, the most remarkable response was the up-regulation of iron-related genes. We demonstrate that the pSymA plasmid and specifically genes required for the biosynthesis of the siderophore rhizobactin 1021 are essential for swarming of a S. meliloti wild-type strain but not in a fadD mutant. Moreover, high iron conditions inhibit swarming of the wild-type strain but not in mutants lacking either the iron limitation response regulator RirA or FadD. Conclusions The present work represents the first transcriptomic study of rhizobium growth on surfaces including swarming inducing conditions. The results have revealed major changes in the physiology of S. meliloti cells grown on a surface relative to liquid cultures. Moreover, analysis of genes responding to swarming inducing conditions led to the demonstration that iron and genes involved in rhizobactin 1021 synthesis play a role in the surface motility shown by S. meliloti which can be circumvented in a fadD mutant. This work opens a way to the identification of new traits and regulatory networks involved in swarming by rhizobia.

  9. 局部应用 VEGF 对失神经皮瓣中性粒细胞趋化性影响的实验研究%EXPERIMENTAL STUDY ON EFFECT OF VASCULAR ENDOTHELIAL GROWTH FACTOR ON NEU-TROPHIL CHEMOTAXIS OF DENERVATED INFECT SKIN FLAP

    Institute of Scientific and Technical Information of China (English)

    褚立明; 孙丽霞; 穆树林; 张明; 张彦军; 贺房勇

    2015-01-01

    Objective To investigate the effect of Vascular Endothelial Growth Factor in resisting infection in soft tissue in a rat denervated infect flap model.Methods An island pedicle flap measured 2×2cm was raised on the right abdomen of sixty Wister rats,which were divided into three groups.All flap received in-tradermal inoculation of 107 Staphylococcus aureus,and the animals were observed for 96 hours.Three methods were used in the experiment to observe the effect of denervation:Leukocyte counts,the ratio of viable leukocytes and chemotaxis assay.Results The numbers of mobilized leukocytes within each wound cylinder space flap were not statistically different (P >0.05).The ratio of viable leukocytes by chemotaxis assay in prolong denervation group were significantly changed compared with control group (P 0.05);而在白细胞活力、中性粒细胞趋化性等指标测定中,慢性失神经组较对照组差异有统计学意义(P <0.01);VEGF 治疗组较慢性失神经组差异有统计学意义(P <0.01)。结论软组织失去神经支配后,降低了白细胞的功能。而血管内皮生长因子能改善皮瓣微循环,并有增强白细胞功能的作用。

  10. Gene transcription changes in asthmatic chronic rhinosinusitis with nasal polyps and comparison to those in atopic dermatitis.

    Directory of Open Access Journals (Sweden)

    Douglas A Plager

    Full Text Available BACKGROUND: Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD, which is also closely related to asthma. METHODS/PRINCIPAL FINDINGS: Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11 that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13 that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD. CONCLUSIONS/SIGNIFICANCE: Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation

  11. Gene therapy in periodontics

    OpenAIRE

    Anirban Chatterjee; Nidhi Singh; Mini Saluja

    2013-01-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person′s genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ′the use of genes as medicine′. It...

  12. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  13. Does Gene Translocation Accelerate the Evolution of Laterally Transferred Genes?

    OpenAIRE

    Hao, Weilong; Golding, G. Brian

    2009-01-01

    Lateral gene transfer (LGT) and gene rearrangement are essential for shaping bacterial genomes during evolution. Separate attention has been focused on understanding the process of lateral gene transfer and the process of gene translocation. However, little is known about how gene translocation affects laterally transferred genes. Here we have examined gene translocations and lateral gene transfers in closely related genome pairs. The results reveal that translocated genes undergo elevated ra...

  14. Influence of oxygen limitation, absence of the cytochrome bc(1) complex and low pH on global gene expression in Gluconobacter oxydans 621H using DNA microarray technology.

    Science.gov (United States)

    Hanke, Tanja; Richhardt, Janine; Polen, Tino; Sahm, Hermann; Bringer, Stephanie; Bott, Michael

    2012-02-10

    The genome-wide transcriptional responses of the strictly aerobic α-proteobacterium Gluconobacter oxydans 621H to oxygen limitation, to the absence of the cytochrome bc(1) complex, and to low pH were studied using DNA microarray analyses. Oxygen limitation caused expression changes of 486 genes, representing 20% of the chromosomal genes. Genes with an increased mRNA level included those for terminal oxidases, the cytochrome bc(1) complex, transhydrogenase, two alcohol dehydrogenases, heme biosynthesis, PTS proteins, proteins involved in cyclic diGMP synthesis and degradation, two sigma factors, flagella and chemotaxis proteins, several stress proteins, and a putative exporter protein. The downregulated genes comprised those for respiratory dehydrogenases, enzymes of central metabolism, PQQ biosynthesis, outer membrane receptors, Sec proteins, and proteins involved in transcription and translation. A ΔqrcABC mutant of G. oxydans showed a growth defect during cultivation on mannitol at pH 4 under oxygen saturation. Comparison of the transcriptomes of this mutant versus the wild type under these conditions revealed 51 differentially expressed genes. Interestingly, almost all of the 45 genes with increased expression in the ΔqrcABC mutant at pH 4 were also upregulated in the wild type grown at pH 6 under oxygen limitation. These results support an active role of the cytochrome bc(1) complex in G. oxydans respiration. The transcriptome comparison of G. oxydans wild type at pH 4 versus pH 6 in mannitol medium under oxygen-saturated conditions uncovered only 72 differentially expressed genes. The 35 upregulated genes included those for cytochrome bd oxidase, major polyol dehydrogenase, iron storage and oxidative stress proteins. Among the 37 downregulated genes were some encoding enzymes dealing with carbon dioxide, such as biotin carboxylase, biotin carboxyl carrier protein, and carboanhydrase. These results give first insights into global transcriptional responses of

  15. Conserved synteny at the protein family level reveals genes underlying Shewanella species cold tolerance and predicts their novel phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Karpinets, Tatiana V.; Obraztsova, Anna; Wang, Yanbing; Schmoyer, Denise D.; Kora, Guruprasad; Park, Byung H.; Serres, Margrethe H.; Romine, Margaret F.; Land, Miriam L.; Kothe, Terence B.; Fredrickson, Jim K.; Nealson, Kenneth H.; Uberbacher, Edward

    2010-03-01

    Bacteria of the genus Shewanella can thrive in different environments and demonstrate significant variability in their metabolic and ecophysiological capabilities including cold and salt tolerance. Genomic characteristics underlying this variability across species are largely unknown. In this study we address the problem by a comparison of the physiological, metabolic and genomic characteristics of 19 sequenced Shewanella species. We have employed two novel approaches based on association of a phenotypic trait with the number of the trait-specific protein families (Pfam domains) and on the conservation of synteny (order in the genome) of the trait-related genes. Our first approach is top-down and involves experimental evaluation and quantification of the species’ cold tolerance followed by identification of the correlated Pfam domains and genes with a conserved synteny. The second, a bottom-up approach, predicts novel phenotypes of the species by calculating profiles of each Pfam domain among their genomes and following pair-wise correlation of the profiles and their network clustering. Using the first approach we find a link between cold and salt tolerance of the species and the presence in the genome of a Na+/H+ antiporter gene cluster. Other cold tolerance related genes includes peptidases, chemotaxis sensory transducer proteins, a cysteine exporter, and helicases. Using the bottom-up approach we found several novel phenotypes in the newly sequenced Shewanella species, including degradation of aromatic compounds by an aerobic hybrid pathway in S. woodyi, degradation of ethanolamine by S. benthica, and propanediol degradation by S. putrefaciens CN32 and S. sp. W3-18-1.

  16. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.;

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related to...... cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  17. Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects

    Directory of Open Access Journals (Sweden)

    Soronen Jarkko

    2012-04-01

    Full Text Available Abstract Background To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. Methods Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 hours of intravenously maintained euglycemic hyperinsulinemia from 9 insulin-resistant and 11 insulin-sensitive females. Gene expression was measured using Affymetrix HG U133 Plus 2 microarrays and qRT-PCR. Microarray data and pathway analyses were performed with Chipster v1.4.2 and by using in-house developed nonparametric pathway analysis software. Results The most prominent difference in gene expression of the insulin-resistant group during hyperinsulinemia was reduced transcription of nuclear genes involved in mitochondrial respiration (mitochondrial respiratory chain, GO:0001934. Inflammatory pathways with complement components (inflammatory response, GO:0006954 and cytokines (chemotaxis, GO:0042330 were strongly up-regulated in insulin-resistant as compared to insulin-sensitive subjects both before and during hyperinsulinemia. Furthermore, differences were observed in genes contributing to fatty acid, cholesterol and triglyceride metabolism (FATP2, ELOVL6, PNPLA3, SREBF1 and in genes involved in regulating lipolysis (ANGPTL4 between the insulin-resistant and -sensitive subjects especially during hyperinsulinemia. Conclusions The major finding of this study was lower expression of mitochondrial respiratory pathway and defective induction of lipid metabolism pathways by insulin in insulin-resistant subjects. Moreover, the study reveals several novel genes whose aberrant regulation is associated with the obese insulin-resistant phenotype.

  18. Genes underlying altruism

    OpenAIRE

    Thompson, Graham J.; Hurd, Peter L.; Crespi, Bernard J.

    2013-01-01

    William D. Hamilton postulated the existence of ‘genes underlying altruism’, under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system ...

  19. Cochlear Gene Therapy

    OpenAIRE

    Lustig, Lawrence R.; Akil, Omar

    2012-01-01

    The purpose of this review is to highlight recent advances in cochlear gene therapy over the past several years. Cochlear gene therapy has undergone tremendous advances over the past decade. Beginning with some groundbreaking work in 2005 documenting hair cell regeneration using virallymediated delivery of the mouse atonal 1 gene, gene therapy is now being explored as a possible treatment for a variety of causes of hearing loss.

  20. Supervised clustering of genes

    OpenAIRE

    Dettling, Marcel; Bühlmann, Peter

    2002-01-01

    Background We focus on microarray data where experiments monitor gene expression in different tissues and where each experiment is equipped with an additional response variable such as a cancer type. Although the number of measured genes is in the thousands, it is assumed that only a few marker components of gene subsets determine the type of a tissue. Here we present a new method for finding such groups of genes by directly incorporating the response variables into the grouping process, yiel...

  1. Discovering genes underlying QTL

    International Nuclear Information System (INIS)

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  2. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  3. A Pilot Study of Gene/Gene and Gene/Environment Interactions in Alzheimer Disease

    OpenAIRE

    Ghebranious, Nader; Mukesh, Bickol; Giampietro, Philip F.; Glurich, Ingrid; Mickel, Susan F.; Waring, Stephen C.; Catherine A McCarty

    2011-01-01

    Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD.

  4. Identification of chemosensory proteins for trichloroethylene in Pseudomonas aeruginosa

    OpenAIRE

    Shitashiro, Maiko; Tanaka, Hirohide; Hong, Chang Soo; Kuroda, Akio; Takiguchi, Noboru; Ohtake, Hisao; Kato, Junichi

    2005-01-01

    The involvement of the chemotaxis gene cluster 1 (cheYZABW) and cheR in repellent responses of Pseudomonas aeruginosa to trichloroethylene (TCE) is described and three methyl-accepting chemotaxis proteins (MCPs) for TCE are identified. TCE chemotaxis assays of a number of deletion-insertion mutants of P. aeruginosa PAO1 revealed that the chemotaxis gene cluster 1 and cheR are required for negative chemotaxis to TCE. Mutant strains which contained deletions in pctA, pctB and pctC showed decrea...

  5. Modelling prokaryote gene content

    Directory of Open Access Journals (Sweden)

    Edward Susko

    2006-01-01

    Full Text Available The patchy distribution of genes across the prokaryotes may be caused by multiple gene losses or lateral transfer. Probabilistic models of gene gain and loss are needed to distinguish between these possibilities. Existing models allow only single genes to be gained and lost, despite the empirical evidence for multi-gene events. We compare birth-death models (currently the only widely-used models, in which only one gene can be gained or lost at a time to blocks models (allowing gain and loss of multiple genes within a family. We analyze two pairs of genomes: two E. coli strains, and the distantly-related Archaeoglobus fulgidus (archaea and Bacillus subtilis (gram positive bacteria. Blocks models describe the data much better than birth-death models. Our models suggest that lateral transfers of multiple genes from the same family are rare (although transfers of single genes are probably common. For both pairs, the estimated median time that a gene will remain in the genome is not much greater than the time separating the common ancestors of the archaea and bacteria. Deep phylogenetic reconstruction from sequence data will therefore depend on choosing genes likely to remain in the genome for a long time. Phylogenies based on the blocks model are more biologically plausible than phylogenies based on the birth-death model.

  6. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  7. Evaluating gene × gene and gene × smoking interaction in rheumatoid arthritis using candidate genes in GAW15

    OpenAIRE

    Mei Ling; Li Xiaohui; Yang Kai; Cui Jinrui; Fang Belle; Guo Xiuqing; Rotter Jerome I

    2007-01-01

    Abstract We examined the potential gene × gene interactions and gene × smoking interactions in rheumatoid arthritis (RA) using the candidate gene data sets provided by Genetic Analysis Workshop 15 Problem 2. The multifactor dimensionality reduction (MDR) method was used to test gene × gene interactions among candidate genes. The case-only sample was used to test gene × smoking interactions. The best predictive model was the single-locus model with single-nucleotide polymorphism (SNP) rs247660...

  8. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets

    KAUST Repository

    Najera, Julia A.

    2016-04-23

    Background Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. Results We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. Conclusions Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.

  9. In-vitro activation of cytotoxic T lymphocytes by fusion of mouse hepatocellular carcinoma cells and lymphotactin gene-modified dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the in-vitro activation of cytotoxic T lymphocytes (CTLs) by fusion of mouse hepatocellular carcinoma (HCC) cells and lymphotactin gene-modified dendritic cells (DCs).METHODS: Lymphotactin gene modified DCs (DCLptn) were prepared by lymphotactin recombinant adenovirus transduction of mature DCs which differentiated from mouse bone marrow cells by stimulation with granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-α). DCLptn and H22 fusion was prepared using 50% PEG. Lymphotactin gene and protein expression levels were measured by RT-PCR and ELISA, respectively. Lymphotactin chemotactic responses were examined by in-vitro chemotaxis assay. In-vitro activation of CTLs by DCLptn/H22 fusion was measured by detecting CD25 expression and cytokine production after autologous T cell stimulation. Cytotoxic function of activated T lymphocytes stimulated with DCLptn/H22 cells was determined by LDH cytotoxicity assay.RESULTS: Lymphotactin gene could be efficiently transduced to DCs by adenovirus vector and showed an effective biological activity. After fusion, the hybrid DCLptn/H22 cells acquired the phenotypes of both DCLptn and H22 cells. In T cell proliferation assay, flow cytometry showed a very high CD25 expression, and cytokine release assay showed a significantly higher concentration of IFN-γ and IL-2 in DCLptn/H22 group than in DCLptn, DCLptn+H22, DC/H22 or H22 groups. Cytotoxicity assay revealed that T cells derived from DCLptn/H22 group had much higher anti-tumor activity than those derived from DCLptn, H22, DCLptn + H22, DC/H22 groups.CONCLUSION: Lymphotactin gene-modified dendritoma induces T-cell proliferation and strong CTL reaction against allogenic HCC cells. Immunization-engineered fusion hybrid vaccine is an attractive strategy in prevention and treatment of HCC metastases.

  10. The effect of aging and caloric restriction on murine CD8+ T cell chemokine receptor gene expression

    Directory of Open Access Journals (Sweden)

    Mo RuRan

    2007-11-01

    Full Text Available Abstract Background The mechanism explaining the increased disease susceptibility in aging is not well understood. CD8+ T cells are crucial in anti-viral and anti-tumor responses. Although the chemokine system plays a critical role in CD8+ T cell function, very little is known about the relationship between aging and the T cell chemokine system. Results In this study we have examined the effect of aging on murine CD8+ T cell chemokine receptor gene expression. Freshly isolated splenic CD8+ T cells from old C57BL/6 mice were found to have higher CCR1, CCR2, CCR4, CCR5 and CXCR5, and lower CCR7 gene expression compared to their younger cohort. Anti-CD3/anti-CD28 stimulation elicited a similar robust chemokine receptor response from young and old CD8+ T cells. Western blot analyses confirmed elevated protein level of CCR4 and CCR5 in aged CD8+ T cells. Increases in T cell CCR1 and CCR5 expression also correlate to increased in vitro chemotaxis response to macrophage-inflammatory protein-1 α(MIP-1α. Finally, caloric restriction selectively prevents the loss of CD8+ T cell CCR7 gene expression in aging to the level that is seen in young CD8+ T cells. Conclusion These findings are consistent with the notion that aging exists in a state of low grade pro-inflammatory environment. In addition, our results provide a potential mechanism for the reported aging-associated impaired T cell lymphoid homing and allograft response, and reduced survival in sepsis.

  11. Staphylococcus aureus Biofilm and Planktonic cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes

    Directory of Open Access Journals (Sweden)

    Olerud John E

    2011-06-01

    Full Text Available Abstract Background Many chronic diseases, such as non-healing wounds are characterized by prolonged inflammation and respond poorly to conventional treatment. Bacterial biofilms are a major impediment to wound healing. Persistent infection of the skin allows the formation of complex bacterial communities termed biofilm. Bacteria living in biofilms are phenotypically distinct from their planktonic counterparts and are orders of magnitude more resistant to antibiotics, host immune response, and environmental stress. Staphylococcus aureus is prevalent in cutaneous infections such as chronic wounds and is an important human pathogen. Results The impact of S. aureus soluble products in biofilm-conditioned medium (BCM or in planktonic-conditioned medium (PCM on human keratinocytes was investigated. Proteomic analysis of BCM and PCM revealed differential protein compositions with PCM containing several enzymes involved in glycolysis. Global gene expression of keratinocytes exposed to biofilm and planktonic S. aureus was analyzed after four hours of exposure. Gene ontology terms associated with responses to bacteria, inflammation, apoptosis, chemotaxis, and signal transduction were enriched in BCM treated keratinocytes. Several transcripts encoding cytokines were also upregulated by BCM after four hours. ELISA analysis of cytokines confirmed microarray results at four hours and revealed that after 24 hours of exposure, S. aureus biofilm induced sustained low level cytokine production compared to near exponential increases of cytokines in planktonic treated keratinocytes. The reduction in cytokines produced by keratinocytes exposed to biofilm was accompanied by suppressed phosphorylation of MAPKs. Chemical inhibition of MAPKs did not drastically reduce cytokine production in BCM-treated keratinocytes suggesting that the majority of cytokine production is mediated through MAPK-independent mechanisms. Conclusions Collectively the results indicate that S

  12. Cancer gene therapy

    OpenAIRE

    Mitrović Tatjana; Radulović Siniša

    2005-01-01

    Cancer gene therapy can be defined as transfer of nucleic acids into tumor or normal cells with aim to eradicate or reduce tumor mass by direct killing of cells, immunomodulation or correction of genetic errors, and reversion of malignant status. Initially started with lots of optimism and enthusiasm, cancer gene therapy has shown limited success in treatment of patients. This review highlights current limitations and almost endless possibilities of cancer gene therapy. The major difficulty i...

  13. Regulation of gene expression

    International Nuclear Information System (INIS)

    In order to define in molecular terms the mechanisms controlling expression of specific genes in mammalian cells, how gene expression is activated, how tissue-specific expression is effected, how expression is modulated by hormones and other specific effectors, and how genetic control mechanisms are altered in the dysfunction of gene expression in cells transformed to malignancy were studied. Much of this work has focused on expression of the rat liver enzyme tyrosine aminotransferase

  14. [The gene or genes of allergic asthma?].

    Science.gov (United States)

    Demoly, P; Bousquet, J; Godard, P; Michel, F B

    1993-05-15

    Asthma is a multifactorial disease in which the hereditary component has been demonstrated by familial and identical twin studies. Allergy is important in the aetiology of asthma and is characterized by a hyperreaction to allergens triggering predominantly the immunoglobulines E. The levels of these antibodies are found to be elevated even in non allergic asthmatics. The majority of genetic research in this area is focused on either the genes of the specific immune response or that of the non allergic response. These are the genes of the class II MHC, and the APY gene on chromosome 11q respectively. The modern techniques of molecular genetics and in particular those of inverse genetics have recently contributed to a more comprehensive understanding of this disease. PMID:8316547

  15. Genome-wide identification of HrpL-regulated genes in the necrotrophic phytopathogen Dickeya dadantii 3937.

    Directory of Open Access Journals (Sweden)

    Shihui Yang

    Full Text Available BACKGROUND: Dickeya dadantii is a necrotrophic pathogen causing disease in many plants. Previous studies have demonstrated that the type III secretion system (T3SS of D. dadantii is required for full virulence. HrpL is an alternative sigma factor that binds to the hrp box promoter sequence of T3SS genes to up-regulate their expression. METHODOLOGY/PRINCIPAL FINDINGS: To explore the inventory of HrpL-regulated genes of D. dadantii 3937 (3937, transcriptome profiles of wild-type 3937 and a hrpL mutant grown in a T3SS-inducing medium were examined. Using a cut-off value of 1.5, significant differential expression was observed in sixty-three genes, which are involved in various cellular functions such as type III secretion, chemotaxis, metabolism, regulation, and stress response. A hidden Markov model (HMM was used to predict candidate hrp box binding sites in the intergenic regions of 3937, including the promoter regions of HrpL-regulated genes identified in the microarray assay. In contrast to biotrophic phytopathgens such as Pseudomonas syringae, among the HrpL up-regulated genes in 3937 only those within the T3SS were found to contain a hrp box sequence. Moreover, direct binding of purified HrpL protein to the hrp box was demonstrated for hrp box-containing DNA fragments of hrpA and hrpN using the electrophoretic mobility shift assay (EMSA. In this study, a putative T3SS effector DspA/E was also identified as a HrpL-upregulated gene, and shown to be translocated into plant cells in a T3SS-dependent manner. CONCLUSION/SIGNIFICANCES: We provide the genome-wide study of HrpL-regulated genes in a necrotrophic phytopathogen (D. dadantii 3937 through a combination of transcriptomics and bioinformatics, which led to identification of several effectors. Our study indicates the extent of differences for T3SS effector protein inventory requirements between necrotrophic and biotrophic pathogens, and may allow the development of different strategies for

  16. Delivery Systems in Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    Liu Hu; Anas El-Aneed; Cui Guohui

    2005-01-01

    1 Gene therapy Gene therapy includes the treatment of both genetically based and infectious diseases by introducing genetic materials which have therapeutic effects[1~3]. In its simplest terms, a wild type gene (which is non-functional in the cell leading to disease development) is introduced into the somatic cell lacking this gene to restore the normal gene function in this cell. Many gene therapy strategies, however, utilize genes to destroy specific cells.

  17. Gene Conversion and Evolution of Gene Families: An Overview

    OpenAIRE

    Tomoko Ohta

    2010-01-01

    The importance of gene conversion for the evolution of gene families is reviewed. Four problems concerning gene conversion, i.e., concerted evolution, generation of useful variation, deleterious effects, and relation to neofunctionalization, are discussed by surveying reported examples of evolving gene families. Emphasis is given toward understanding interactive effects of gene conversion and natural selection.

  18. Your Genes, Your Choices

    Science.gov (United States)

    Table of Contents Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social issues that are ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

  19. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function

    OpenAIRE

    Warde-Farley, David; Sylva L. Donaldson; Comes, Ovi; Zuberi, Khalid; Badrawi, Rashad; Chao, Pauline; Franz, Max; Grouios, Chris; Kazi, Farzana; Lopes, Christian Tannus; Maitland, Anson; Mostafavi, Sara; Montojo, Jason; Shao, Quentin; Wright, George

    2010-01-01

    GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis t...

  20. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    OpenAIRE

    Wold, William S.M.; Toth, Karoly

    2013-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vector...

  1. Methanogenesis and methane genes

    International Nuclear Information System (INIS)

    An overview of the pathways leading to methane biosynthesis is presented. The steps investigated to date by gene cloning and DNA sequencing procedures are identified and discussed. The primary structures of component C of methyl coenzyme M reductase encoded by mcr operons in different methanogens are compared. Experiments to detect the primary structure of the genes encoding F420 reducing hydrogenase (frhABG) and methyl hydrogen reducing hydrogenase (mvhDGA) in methanobacterium thermoautotrophicum strain H are compared with each other and with eubacterial hydrogenase encoding genes. A biotechnological use for hydrogenases from hypermorphillic archaebacteria is suggested. (author)

  2. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to...... mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the...

  3. Endurance performance: genes or gene combinations?

    OpenAIRE

    Gómez Gallego, Félix; Santiago Dorrego, Catalina; González-Freire, Marta; Muniesa Ferrero, Carlos Alberto; Fernández del Valle, María; Pérez Ruiz, Margarita; Foster, Carl; Lucía Mulas, Alejandro

    2009-01-01

    We assessed the possible association between variants of the genes encoding for the angiotensin-converting enzyme ( ACE) and alpha-actinin-3 ( ACTN3) (both individually and combined) and several endurance phenotypic traits, e.g., peak power output (PPO), ventilatory (VT) and respiratory compensation threshold (RCT), among others, in professional road cyclists and sedentary controls (n = 46 each). We applied an ANCOVA test using the aforementioned phenotype traits as dependent variables, ACE a...

  4. Differentiation inducing factor-1 (DIF-1) induces gene and protein expression of the Dictyostelium nuclear calmodulin-binding protein nucleomorphin.

    Science.gov (United States)

    O'Day, Danton H; Poloz, Yekaterina; Myre, Michael A

    2009-02-01

    The nucleomorphin gene numA1 from Dictyostelium codes for a multi-domain, calmodulin binding protein that regulates nuclear number. To gain insight into the regulation of numA, we assessed the effects of the stalk cell differentiation inducing factor-1 (DIF-1), an extracellular signalling molecule, on the expression of numA1 RNA and protein. For comparison, the extracellular signalling molecules cAMP (mediates chemotaxis, prestalk and prespore differentiation) and ammonia (NH(3)/NH(4)(+); antagonizes DIF) were also studied. Starvation, which is a signal for multicellular development, results in a greater than 80% decrease in numA1 mRNA expression within 4 h. Treatment with ammonium chloride led to a greater than 90% inhibition of numA1 RNA expression within 2 h. In contrast, the addition of DIF-1 completely blocked the decrease in numA1 gene expression caused by starvation. Treatment of vegetative cells with cAMP led to decreases in numA1 RNA expression that were equivalent to those seen with starvation. Western blotting after various morphogen treatments showed that the maintenance of vegetative levels of numA1 RNA by DIF-1 in starved cells was reflected in significantly increased numA1 protein levels. Treatment with cAMP and/or ammonia led to decreased protein expression and each of these morphogens suppressed the stimulatory effects of DIF-1. Protein expression levels of CBP4a, a calcium-dependent binding partner of numA1, were regulated in the same manner as numA1 suggesting this potential co-regulation may be related to their functional relationship. NumA1 is the first calmodulin binding protein shown to be regulated by developmental morphogens in Dictyostelium being upregulated by DIF-1 and down-regulated by cAMP and ammonia. PMID:19000924

  5. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  6. Genes underlying altruism.

    Science.gov (United States)

    Thompson, Graham J; Hurd, Peter L; Crespi, Bernard J

    2013-01-01

    William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals. PMID:24132092

  7. What Is a Gene?

    Science.gov (United States)

    ... Quizzes Kids' Dictionary of Medical Words En Español What Other Kids Are Reading Back-to-School Butterflies? ... Got Homework? Here's Help White House Lunch Recipes What Is a Gene? KidsHealth > For Kids > What Is ...

  8. Terplex Gene Delivery System.

    Science.gov (United States)

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16243067

  9. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  10. Metastasis Suppressor Genes

    OpenAIRE

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2013-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinica...

  11. Genes and Vocal Learning

    OpenAIRE

    White, Stephanie A.

    2009-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in primates, rodents and birds suggests that FoxP2 and other language-related genes are interactors in the neuromolecular networks that underlie subsystems ...

  12. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  13. Gene-gene, gene-environment, gene-nutrient interactionsand single nucleotide polymorphisms of inflammatorycytokines

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus (T2DM). The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. Among the recognized markers are interleukin(IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha(TNF-α), C-reactive protein, resistin, adiponectin, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

  14. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.;

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

  15. Hox genes and study of Hox genes in crustacean

    Institute of Scientific and Technical Information of China (English)

    HOU Lin; CHEN Zhijuan; XU Mingyu; LIN Shengguo; WANG Lu

    2004-01-01

    Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

  16. GeneCards Version 3: the human gene integrator.

    Science.gov (United States)

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  17. Introns in higher plant genes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The intron is an important component of eukaryotic gene. Extensive studies have been conducted to get a better understanding of its structure and function. This paper presents a brief review of the structure and function of introns in higher plant genes. It is shown that higher plant introns possess structural properties shared by all eukaryotic introns, however, they also exhibit a striking degree of diversity. The process of intron splicing in higher plant genes involves interaction between multiple cis-acting elements and trans-acting factors, such as 5′ splicing site, 3′ splicing site and many protein factors. The process of intron splicing is an important level at which gene expression is regulated. Especially alternative splicing of intron can regulate time and space of gene expression. In addition, some introns in higher plant genes also regulate gene expression by affecting the pattern of gene expression, enhancing the level of gene expression and driving the gene expression.

  18. Radionuclide reporter gene imaging for cardiac gene therapy

    International Nuclear Information System (INIS)

    In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, ''reporter genes'' transferred into cell nuclei encode for a protein that retains a complementary ''reporter probe'' of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy. Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy. (orig.)

  19. Radionuclide reporter gene imaging for cardiac gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Inubushi, Masayuki [Hokkaido University Graduate School of Medicine, Department of Molecular Imaging, Sapporo (Japan); Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo (Japan)

    2007-06-15

    In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, ''reporter genes'' transferred into cell nuclei encode for a protein that retains a complementary ''reporter probe'' of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy. Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy. (orig.)

  20. Gene therapy: progress and predictions

    OpenAIRE

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of ...

  1. Correlating Expression Data with Gene Function Using Gene Ontology

    Institute of Scientific and Technical Information of China (English)

    LIU,Qi; DENG,Yong; WANG,Chuan; SHI,Tie-Liu; LI,Yi-Xue

    2006-01-01

    Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions.However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.

  2. The gene tree delusion.

    Science.gov (United States)

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  3. Vertebrate gene predictions and the problem of large genes

    DEFF Research Database (Denmark)

    Wang, Jun; Li, ShengTing; Zhang, Yong;

    2003-01-01

    To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistently...... low false-negative rate. The incorporation of similarity information is meant to reduce the false-positive rate, but in doing so it increases the false-negative rate. The crucial variable is gene size (including introns)--genes of the most extreme sizes, especially very large genes, are most likely to...

  4. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  5. Association Between a Prognostic Gene Signature and Functional Gene Sets

    Science.gov (United States)

    Hummel, Manuela; Metzeler, Klaus H.; Buske, Christian; Bohlander, Stefan K.; Mansmann, Ulrich

    2008-01-01

    Background The development of expression-based gene signatures for predicting prognosis or class membership is a popular and challenging task. Besides their stringent validation, signatures need a functional interpretation and must be placed in a biological context. Popular tools such as Gene Set Enrichment have drawbacks because they are restricted to annotated genes and are unable to capture the information hidden in the signature’s non-annotated genes. Methodology We propose concepts to relate a signature with functional gene sets like pathways or Gene Ontology categories. The connection between single signature genes and a specific pathway is explored by hierarchical variable selection and gene association networks. The risk score derived from an individual patient’s signature is related to expression patterns of pathways and Gene Ontology categories. Global tests are useful for these tasks, and they adjust for other factors. GlobalAncova is used to explore the effect on gene expression in specific functional groups from the interaction of the score and selected mutations in the patient’s genome. Results We apply the proposed methods to an expression data set and a corresponding gene signature for predicting survival in Acute Myeloid Leukemia (AML). The example demonstrates strong relations between the signature and cancer-related pathways. The signature-based risk score was found to be associated with development-related biological processes. Conclusions Many authors interpret the functional aspects of a gene signature by linking signature genes to pathways or relevant functional gene groups. The method of gene set enrichment is preferred to annotating signature genes to specific Gene Ontology categories. The strategies proposed in this paper go beyond the restriction of annotation and deepen the insights into the biological mechanisms reflected in the information given by a signature. PMID:19812786

  6. Old genes experience stronger translational selection than young genes.

    Science.gov (United States)

    Yin, Hongyan; Ma, Lina; Wang, Guangyu; Li, Mengwei; Zhang, Zhang

    2016-09-15

    Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age. PMID:27259662

  7. Inferring horizontal gene transfer.

    Directory of Open Access Journals (Sweden)

    Matt Ravenhall

    2015-05-01

    Full Text Available Horizontal or Lateral Gene Transfer (HGT or LGT is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric" methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic" approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events.

  8. GENES BEHIND SMOKE ACTION

    Directory of Open Access Journals (Sweden)

    Vilmos Soós

    2008-09-01

    Full Text Available Smoke can break dormancy and promote seed germination of many plant species. We investigated changes in the gene expression changes after imbibition of light-sensitive Lactuca sativa L. cv. Grand Rapids achenes with dilute smoke water compared to water control samples kept in dark or continuous light. Although no difference was detected in the smoke water vs. water control samples germinated in light, smoke water treatment resulted in the differential display of several expressed sequence tags (ESTs when compared to water control samples kept in dark. The most pronounced fragments isolated correspond to known genes with functions related to cell wall expansion, abscisic acid regulation, regulation of translation, the cell division cycle, carbohydrate metabolism and desiccation tolerance. These data clearly indicate that the smoke water, which stimulates germination of light-sensitive Grand Rapids lettuce seeds in the dark, rapidly affects genes that are essential for cell division, cell wall expansion and mobilization and utilization of nutrients for the resumption of embryo growth. Although the master genes remained unknown, our hope is that the using of maize microarray will reveal the whole molecular background of smoke action.

  9. Ultrasound mediated gene transfection

    Science.gov (United States)

    Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.

    2002-05-01

    Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

  10. Searching for speciation genes

    DEFF Research Database (Denmark)

    Holt, Benjamin George; Côté, Isabelle M; Emerson, Brent C

    2011-01-01

    Closely related species that show clear phenotypic divergence, but without obvious geographic barriers, can provide opportunities to study how diversification can occur when opportunities for allopatric speciation are limited. We examined genetic divergence in the coral reef fish genus Hypoplectr...... evidence for genes that may be associated with colour morphotype in the genus Hypoplectrus....

  11. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V;

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and...

  12. Entrez Gene: gene-centered information at NCBI.

    Science.gov (United States)

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2007-01-01

    Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp. PMID:17148475

  13. Tumor-specific gene expression patterns with gene expression profiles

    Institute of Scientific and Technical Information of China (English)

    RUAN; Xiaogang; LI; Yingxin; LI; Jiangeng; GONG; Daoxiong

    2006-01-01

    Gene expression profiles of 14 common tumors and their counterpart normal tissues were analyzed with machine learning methods to address the problem of selection of tumor-specific genes and analysis of their differential expressions in tumor tissues. First, a variation of the Relief algorithm, "RFE_Relief algorithm" was proposed to learn the relations between genes and tissue types. Then, a support vector machine was employed to find the gene subset with the best classification performance for distinguishing cancerous tissues and their counterparts. After tissue-specific genes were removed, cross validation experiments were employed to demonstrate the common deregulated expressions of the selected gene in tumor tissues. The results indicate the existence of a specific expression fingerprint of these genes that is shared in different tumor tissues, and the hallmarks of the expression patterns of these genes in cancerous tissues are summarized at the end of this paper.

  14. Dominance from the perspective of gene-gene and gene-chemical interactions.

    Science.gov (United States)

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe. PMID:26613610

  15. Gene doping in modern sport.

    Directory of Open Access Journals (Sweden)

    MAREK SAWCZUK

    2009-01-01

    Full Text Available Background: The subject of this paper is gene doping, which should be understood as "he non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". The authors of this work, based on the review of literature and previous research, make an attempt at wider characterization of gene doping and the discussion of related potential threats.Methods: This is a comprehensive survey of literature on the latest applications of molecular biology in medicine. The analysis involves a dozen scientific databases examined in order to find genes used in gene therapy and potentially useful in gene doping. Results: The obtained results enable better recognition of gene doping and indicate genes used in medicine that could be used in gene doping. This paper describes potential effects of their use and associated risk, and predicts the possible developments of gene doping in the future. Conclusion: Gene doping is undoubtedly a part of modern sport. Although WADA included gene doping on the list of banned methods as early as 2004, as previously stated above, it has not managed to develop efficient methods of detection.

  16. A bioinformatics insight to rhizobial globins: gene identification and mapping, polypeptide sequence and phenetic analysis, and protein modeling. [v1; ref status: indexed, http://f1000r.es/5ai

    Directory of Open Access Journals (Sweden)

    Reinier Gesto-Borroto

    2015-05-01

    Full Text Available Globins (Glbs are proteins widely distributed in organisms. Three evolutionary families have been identified in Glbs: the M, S and T Glb families. The M Glbs include flavohemoglobins (fHbs and single-domain Glbs (SDgbs; the S Glbs include globin-coupled sensors (GCSs, protoglobins and sensor single domain globins, and the T Glbs include truncated Glbs (tHbs. Structurally, the M and S Glbs exhibit 3/3-folding whereas the T Glbs exhibit 2/2-folding. Glbs are widespread in bacteria, including several rhizobial genomes. However, only few rhizobial Glbs have been characterized. Hence, we characterized Glbs from 62 rhizobial genomes using bioinformatics methods such as data mining in databases, sequence alignment, phenogram construction and protein modeling. Also, we analyzed soluble extracts from Bradyrhizobium japonicum USDA38 and USDA58 by (reduced + carbon monoxide (CO minus reduced differential spectroscopy. Database searching showed that only fhb, sdgb, gcs and thb genes exist in the rhizobia analyzed in this work. Promoter analysis revealed that apparently several rhizobial glb genes are not regulated by a -10 promoter but might be regulated by -35 and Fnr (fumarate-nitrate reduction regulator-like promoters. Mapping analysis revealed that rhizobial fhbs and thbs are flanked by a variety of genes whereas several rhizobial sdgbs and gcss are flanked by genes coding for proteins involved in the metabolism of nitrates and nitrites and chemotaxis, respectively. Phenetic analysis showed that rhizobial Glbs segregate into the M, S and T Glb families, while structural analysis showed that predicted rhizobial SDgbs and fHbs and GCSs globin domain and tHbs fold into the 3/3- and 2/2-folding, respectively. Spectra from B. japonicum USDA38 and USDA58 soluble extracts exhibited peaks and troughs characteristic of bacterial and vertebrate Glbs thus indicating that putative Glbs are synthesized in B. japonicum USDA38 and USDA58.

  17. Eukaryotic gene prediction using GeneMark.hmm-E and GeneMark-ES.

    Science.gov (United States)

    Borodovsky, Mark; Lomsadze, Alex

    2011-09-01

    This unit describes how to use the gene-finding programs GeneMark.hmm-E and GeneMark-ES for finding protein-coding genes in the genomic DNA of eukaryotic organisms. These bioinformatics tools have been demonstrated to have state-of-the-art accuracy for many fungal, plant, and animal genomes, and have frequently been used for gene annotation in novel genomic sequences. An additional advantage of GeneMark-ES is that the problem of algorithm parameterization is solved automatically, with parameters estimated by iterative self-training (unsupervised training). PMID:21901742

  18. Genes, stress, and depression.

    Science.gov (United States)

    Wurtman, Richard J

    2005-05-01

    A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls

  19. On atavisms and atavistic genes.

    Science.gov (United States)

    Cantú, J M; Ruiz, C

    1985-01-01

    The authors propose the term atavistic to designate a gene producing an ancestral phenotype (atavism). Several examples are presented, and the possible origin of atavistic genes, as well as their pathological implications discussed. PMID:3879145

  20. Gene Testing for Hereditary Ataxia

    Science.gov (United States)

    FAQ NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT... Gene Testing for Hereditary Ataxia This fact sheet provides an overview of gene testing for ataxia. It also addresses commonly asked ...

  1. Genes and human brain evolution

    OpenAIRE

    Geschwind, Daniel H.; Konopka, Genevieve

    2012-01-01

    Several genes were duplicated during human evolution. It seems that one such duplication gave rise to a gene that may have helped to make human brains bigger and more adaptable than those of our ancestors.

  2. Genes That Influence Blood Pressure

    Science.gov (United States)

    ... Research Matters NIH Research Matters September 26, 2011 Genes that Influence Blood Pressure In one of the ... 16 previously unknown variations. Six were found in genes already suspected of regulating blood pressure. The remaining ...

  3. Gene therapy of liver cancer

    OpenAIRE

    Hernandez-Alcoceba, R. (Rubén); B. Sangro; Prieto, J.

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/pro-drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition, gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reac...

  4. Gene doping in modern sport.

    OpenAIRE

    MAREK SAWCZUK; AGNIESZKA MACIEJEWSKA; PAWEL CIESZCZYK,

    2009-01-01

    Background: The subject of this paper is gene doping, which should be understood as "he non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". The authors of this work, based on the review of literature and previous research, make an attempt at wider characterization of gene doping and the discussion of related potential threats.Methods: This is a comprehensive survey of literature on the latest app...

  5. Human housekeeping genes are compact

    OpenAIRE

    Eisenberg, Eli; Erez Y. Levanon

    2003-01-01

    We identify a set of 575 human genes that are expressed in all conditions tested in a publicly available database of microarray results. Based on this common occurrence, the set is expected to be rich in "housekeeping" genes, showing constitutive expression in all tissues. We compare selected aspects of their genomic structure with a set of background genes. We find that the introns, untranslated regions and coding sequences of the housekeeping genes are shorter, indicating a selection for co...

  6. Gene therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Chang-tai; Guo Xue-gang; Pan Bo-rong

    2003-01-01

    @@ 1 Introduction We have reviewed the gene therapy in gastrointestinal diseases[1]. Gastric cancer is common in China[2~20] ,and its early diagnosis andtreatment are still difficult up to now[13~36]. The expression of anexogenous gene introduced by gene therapy into patients with gliomascan be monitored non- invasively by positron- emission tomography[4]. In recent years, gene study in cancer is a hotspot, and great progress hasbeen achieved[33~41].

  7. Genes y especies

    Directory of Open Access Journals (Sweden)

    A. G. Sáez

    2009-01-01

    Full Text Available La posibilidad de secuenciar y manipular los genes sigue abriendo fronteras en el estudio de las especies y la especiación. En tiempos recientes particularmente en dos direcciones. Por un lado, la secuenciación del gen COI (y otros en miles de muestras de forma sistemática y masiva, el llamado "DNA barcoding", está revelando una gran cantidad de biodiversidad, en buena medida previamente no sospechada y correspondiente a especies crípticas (morfológicamente irreconocibles. En segundo lugar, el estudio de los genes responsables de los cambios morfológicos nos está haciendo volver a dar una creciente importancia a la selección como motor de la especiación y de la evolución, incluso en presencia de dosis importantes de flujo génico.

  8. Gene and Aging

    Directory of Open Access Journals (Sweden)

    DD Farhud

    2008-09-01

    Full Text Available "nCollection of multiple processes that increase the chronological age of an organism leading to death is defined as aging, and even though important, it is poorly understood. Recent research has shown that aging is due to biochemical and genetic changes, in interaction with environmental effects, including diet and nutrition. Most knowledge on aging is based on ge­netic model system, but its molecular mechanisms are still not very clear. Discoveries in molecular biology have made way to look for candidate genes influencing lifespan. Furthermore, new investigations have stressed on the roles of mitochondria as the major generators and direct targets of reactive oxygen species. This paper reviews some recent literature on genes and ag­ing in model system, then discusses the role of mitochondria and nutrients in human aging.

  9. Gene therapy of cancer and development of therapeutic target gene

    International Nuclear Information System (INIS)

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

  10. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  11. The Cytomegalovirus UL146 Gene Product vCXCL1 Targets Both CXCR1 and CXCR2 as an Agonist

    DEFF Research Database (Denmark)

    Luttichau, H.R.

    2010-01-01

    /NAP-2 and CXCL8/IL-8 in competition binding, calcium mobilization, inositol triphosphate turnover, and chemotaxis assays using CXCR1- and CXCR2-expressing Chinese hamster ovary, 300.19, COS7, and L1.2 cells. The affinities of vCXCL1 for the CXCR1 and CXCR2 receptors were 44 and 5.6 nM, respectively......, as determined in competition binding against radioactively labeled CXCL8. In calcium mobilization, phosphatidylinositol turnover, and chemotaxis assays, vCXCL1 acted as a highly efficacious activator of both receptors, with a rather low potency for the CXCR1 receptor but comparable with CXCL5 and...

  12. The Perils of Gene Patents

    OpenAIRE

    Salzberg, SL

    2012-01-01

    I argue here that gene patents, and patented genetic tests based on them, are a very bad idea. First, I discuss whether genes can reasonably be the subject of patents in the first place; I maintain that the answer is no. Second, I explain how gene patents interfere with scientific progress, slowing down the development of new cures and treatments for genetic diseases.

  13. Globin genes on the move

    OpenAIRE

    Hardison, Ross C.

    2008-01-01

    Recent data published in BMC Biology from the globin gene clusters in platypus, together with data from other species, show that β-globin genes transposed from one chromosomal location to another. This resolves some controversies about vertebrate globin gene evolution but ignites new ones.

  14. Independent Gene Discovery and Testing

    Science.gov (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  15. Ascidian gene-expression profiles

    OpenAIRE

    William R Jeffery

    2002-01-01

    With the advent of gene-expression profiling, a large number of genes can now be investigated simultaneously during critical stages of development. This approach will be particularly informative in studies of ascidians, basal chordates whose genomes and embryology are uniquely suited for mapping developmental gene networks.

  16. Gene therapy for thyroid cancer

    International Nuclear Information System (INIS)

    Gene therapy for thyroid cancer include immunotherapy, suicide gene therapy, tumor suppressor replacement, 131I therapy by sodium/iodide symporter and antisense therapy and so on. Gene therapy has wide perspectives, but there are many problems need to be solved for clinical application

  17. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin;

    2002-01-01

    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  18. Gene therapy for mucopolysaccharidosis

    OpenAIRE

    Ponder, Katherine P.; Haskins, Mark E.

    2007-01-01

    Mucopolysaccharidoses (MPS) are due to deficiencies in activities of lysosomal enzymes that degrade glycosaminoglycans. Some attempts at gene therapy for MPS in animal models have involved intravenous injection of vectors derived from an adeno-associated virus (AAV), adenovirus, retrovirus or a plasmid, which primarily results in expression in liver and secretion of the relevant enzyme into blood. Most vectors can correct disease in liver and spleen, although correction in other organs includ...

  19. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  20. Engineering prokaryotic gene circuits

    OpenAIRE

    Michalodimitrakis, Konstantinos; Isalan, Mark

    2009-01-01

    Engineering of synthetic gene circuits is a rapidly growing discipline, currently dominated by prokaryotic transcription networks, which can be easily rearranged or rewired to give different output behaviours. In this review, we examine both a rational and a combinatorial design of such networks and discuss progress on using in vitro evolution techniques to obtain functional systems. Moving beyond pure transcription networks, more and more networks are being implemented at the level of RNA, t...

  1. Hidden genes in birds

    Czech Academy of Sciences Publication Activity Database

    Hron, Tomáš; Pajer, Petr; Pačes, Jan; Bartůněk, Petr; Elleder, Daniel

    2015-01-01

    Roč. 16, August 18 (2015). ISSN 1465-6906 R&D Projects: GA MŠk(CZ) LK11215; GA MŠk LO1419 Grant ostatní: GA MŠk(CZ) LM2010005 Institutional support: RVO:68378050 Keywords : REPETITIVE SEQUENCES * G/C stretches * avian genes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.810, year: 2014

  2. The ank gene story

    OpenAIRE

    Ryan, Lawrence M

    2000-01-01

    The underlying molecular defect resulting in the abnormal calcification observed in ank/ank mice has been identified. The responsible nonsense mutation affects the protein product of ank, resulting in diminished production of extracellular inorganic pyrophosphate, an important inhibitor of nucleation and of the growth of apatite crystals. The ank gene product is one of several cell membrane proteins, including ectonucleoside triphosphate pyrophosphohydrolase enzymes and alkaline phosphatase, ...

  3. nanosheets for gene therapy

    Science.gov (United States)

    Kou, Zhongyang; Wang, Xin; Yuan, Renshun; Chen, Huabin; Zhi, Qiaoming; Gao, Ling; Wang, Bin; Guo, Zhaoji; Xue, Xiaofeng; Cao, Wei; Guo, Liang

    2014-10-01

    A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.

  4. Extracting gene-gene interactions through curve fitting.

    Science.gov (United States)

    Das, Ranajit; Mitra, Sushmita; Murthy, C A

    2012-12-01

    This paper presents a simple and novel curve fitting approach for generating simple gene regulatory subnetworks from time series gene expression data. Microarray experiments simultaneously generate massive data sets and help immensely in the large-scale study of gene expression patterns. Initial biclustering reduces the search space in the high-dimensional microarray data. The least-squares error between fitting of gene pairs is minimized to extract a set of gene-gene interactions, involving transcriptional regulation of genes. The higher error values are eliminated to retain only the strong interacting gene pairs in the resultant gene regulatory subnetwork. Next the algorithm is extended to a generalized framework to enhance its capability. The methodology takes care of the higher-order dependencies involving multiple genes co-regulating a single gene, while eliminating the need for user-defined parameters. It has been applied to the time-series Yeast data, and the experimental results biologically validated using standard databases and literature. PMID:22997274

  5. Identification of Significant Association and Gene-Gene Interaction of GABA Receptor Subunit Genes in Autism

    OpenAIRE

    Ma, D Q; Whitehead, P. L.; Menold, M M; Martin, E. R.; Ashley-Koch, A. E.; Mei, H; Ritchie, M. D.; Delong, G R; Abramson, R.K.; Wright, H. H.; Cuccaro, M. L.; Hussman, J. P.; Gilbert, J.R.; Pericak-Vance, M A

    2005-01-01

    Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied...

  6. Gene Network Biological Validity Based on Gene-Gene Interaction Relevance

    OpenAIRE

    Francisco Gómez-Vela; Norberto Díaz-Díaz

    2014-01-01

    In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in...

  7. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie

    2014-01-01

    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapte...... describes how gene therapy may be performed using electric pulses to enhance uptake and expression.......Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapter...

  8. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  9. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  10. СHEMOTAXIS OF CHLAMYDOMONAS REINHARDTII TO NITRATE IS CHANGED DURING GAMETOGENESIS

    OpenAIRE

    Ermilova, Elena; Zalutskaya, Zhanneta; Lapina, Tatyana

    2009-01-01

    During sexual differentiation Chlamydomonas reinhardtii changes its chemotactic behavior to nitrate. Unlike vegetative cells and noncompetent pregametes, mature gametes did not show chemotaxis to nitrate. Loss of chemotaxis to nitrate in matingcompetent cells is controlled by gamete-specific genes that are common for both mating-type gametes. Just like gamete formation, the change in chemotaxis mode is controlled by the sequential action of two environmental cues, removal of nitrogen from the...

  11. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Resources Clinical Trials Information Gene Therapy and Cell Therapy Terminology Gene Therapy & Cell Therapy Breakthroughs FAQs Gene Therapy and Cell Therapy Defined Gene Therapy and Cell Therapy for Diseases Sites of ...

  12. Gene Therapy and Children (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Gene Therapy and Children KidsHealth > For Parents > Gene Therapy ... that don't respond to conventional therapies. About Genes Our genes help make us unique. Inherited from ...

  13. Genes and Disease: Prader-Willi Syndrome

    Science.gov (United States)

    ... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... Willi syndrome. PDF version of this page (220K) Gene sequence Genome view see gene locations Entrez Gene ...

  14. Our Blue Gene Experience

    Czech Academy of Sciences Publication Activity Database

    Jakl, Ondřej; Starý, Jiří

    Ostrava : Ústav geoniky AV ČR, 2009 - (Blaheta, R.; Starý, J.), s. 50-54 ISBN 978-80-86407-60-9. [SNA '09 - Seminar on numerical analysis: modelling and simulation of challenging engineering problems. Ostrava (CZ), 02.02.2009-06.02.2009] R&D Projects: GA ČR(CZ) GA105/09/1830 Institutional research plan: CEZ:AV0Z30860518 Keywords : IBM Blue Gene/P * finite element solver * parallel scalability Subject RIV: BA - General Mathematics

  15. Computation in gene networks

    Science.gov (United States)

    Ben-Hur, Asa; Siegelmann, Hava T.

    2004-03-01

    Genetic regulatory networks have the complex task of controlling all aspects of life. Using a model of gene expression by piecewise linear differential equations we show that this process can be considered as a process of computation. This is demonstrated by showing that this model can simulate memory bounded Turing machines. The simulation is robust with respect to perturbations of the system, an important property for both analog computers and biological systems. Robustness is achieved using a condition that ensures that the model equations, that are generally chaotic, follow a predictable dynamics.

  16. Genes and species

    OpenAIRE

    Sáez, Alberto G.

    2009-01-01

    La posibilidad de secuenciar y manipular los genes sigue abriendo fronteras en el estudio de las especies y la especiación. En tiempos recientes particularmente en dos direcciones. Por un lado, la secuenciación del gen COI (y otros) en miles de muestras de forma sistemática y masiva, el llamado "DNA barcoding", está revelando una gran cantidad de biodiversidad, en buena medida previamente no sospechada y correspondiente a especies crípticas (morfológicamente irreconocibles). En segundo lug...

  17. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder. The ...... binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  18. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function.

    Science.gov (United States)

    Warde-Farley, David; Donaldson, Sylva L; Comes, Ovi; Zuberi, Khalid; Badrawi, Rashad; Chao, Pauline; Franz, Max; Grouios, Chris; Kazi, Farzana; Lopes, Christian Tannus; Maitland, Anson; Mostafavi, Sara; Montojo, Jason; Shao, Quentin; Wright, George; Bader, Gary D; Morris, Quaid

    2010-07-01

    GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist. PMID:20576703

  19. Gene Therapy of Cancerous Diseases

    Directory of Open Access Journals (Sweden)

    Valenčáková, A.

    2015-11-01

    Full Text Available Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purpose of explaining effective anti-tumor immune response. Another method is suicide gene therapy, based on introducing viral or bacterial agents to tumor cells, allowing the conversion of a non-toxic compound to a lethal medication. The application of intact suppressor genes to cancer cells will avert their neoplastic behavior and will induce tumor regression. Inhibition of angiogenesis is also a promising strategy for treating oncologic patients. Mesenchymal stem cells can also be used as vectors in targeted gene therapy. An increasing list of experimental evidence shows, that therapeutically modified mesenchymal stem cells in “gene directed enzyme/prodrug therapy” can attack cancer tissue can kill tumor cells, cancer stem cells included. Bacteria are used as anti-cancer agents independently of in combination with conventional therapeutic methods.

  20. PROAPOPTOTIC FUNCTION OF FHIT GENE

    Institute of Scientific and Technical Information of China (English)

    QIU Zhe-fu; HAN De-min; ZHANG Luo; ZHANG Wei

    2006-01-01

    Tumor suppressor gene plays an important role in maintaining the homeostasis between cell loss and growth. Fragile in maintaining the homeostasis between cell loss and growth. Fragile histidine triad (FHIT) gene found recently was studied in a deep going way; it becomes the focus as a result of its roleof ep going way; it becomes the focus as a result of its roleof anti-tumor in human various type of tissue. Due to the high efficiency of FHIT gene benefiting the anti-tumor, it is proposed gh efficiency of FHIT gene benefiting the anti-tumor, it is proposed as a candidate of tumor suppressor gene though there are several opposite opinions.several opposite opinions. We stress the summary of some properties of FHIT gene on proapoptosis according to the published data which showed gene on proapoptosis according to the published data which showed the stronger proapoptotic function of FHIT gene; the apoptosis induced by FHIT depends on the expression level and status of ene; the apoptosis induced by FHIT depends on the expression level and status of FHIT; and FHIT gene can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process e can alternate the cell cycling properties and reduce the tumorigenic potential; the apoptotic process induced by FHIT has no relation to p53 gene. In a ward, in consideration of its multiple functions against malignancies, FHIT in consideration of its multiple functions against malignancies, FHIT gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical et for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.le histidine triad (FHIT) gene; Apoptosis; Tumorigenesis; Tumor suppressor gene deserves attention and exploration as a selective target for searching the mechanism of tumorigenesis and clinical therapeutic applications in further.

  1. Identifying Driver Genes in Cancer by Triangulating Gene Expression, Gene Location, and Survival Data

    Science.gov (United States)

    Rouam, Sigrid; Miller, Lance D; Karuturi, R Krishna Murthy

    2014-01-01

    Driver genes are directly responsible for oncogenesis and identifying them is essential in order to fully understand the mechanisms of cancer. However, it is difficult to delineate them from the larger pool of genes that are deregulated in cancer (ie, passenger genes). In order to address this problem, we developed an approach called TRIAngulating Gene Expression (TRIAGE through clinico-genomic intersects). Here, we present a refinement of this approach incorporating a new scoring methodology to identify putative driver genes that are deregulated in cancer. TRIAGE triangulates – or integrates – three levels of information: gene expression, gene location, and patient survival. First, TRIAGE identifies regions of deregulated expression (ie, expression footprints) by deriving a newly established measure called the Local Singular Value Decomposition (LSVD) score for each locus. Driver genes are then distinguished from passenger genes using dual survival analyses. Incorporating measurements of gene expression and weighting them according to the LSVD weight of each tumor, these analyses are performed using the genes located in significant expression footprints. Here, we first use simulated data to characterize the newly established LSVD score. We then present the results of our application of this refined version of TRIAGE to gene expression data from five cancer types. This refined version of TRIAGE not only allowed us to identify known prominent driver genes, such as MMP1, IL8, and COL1A2, but it also led us to identify several novel ones. These results illustrate that TRIAGE complements existing tools, allows for the identification of genes that drive cancer and could perhaps elucidate potential future targets of novel anticancer therapeutics. PMID:25949096

  2. Immunity-related genes and gene families in Anopheles gambiae.

    Science.gov (United States)

    Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C

    2002-10-01

    We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. PMID:12364793

  3. Horizontal gene transfer in fungi

    OpenAIRE

    Fitzpatrick, David A.

    2011-01-01

    Horizontal gene transfer (HGT) is frequently observed in prokaryotes and until recently was assumed to be of limited importance to eukaryotes. However, there is an increasing body of evidence to suggest that HGT is an important mechanism in eukaryotic genome evolution, particularly in unicellular organisms. The transfer of individual genes, gene clusters or entire chromosomes can have significant impacts on niche specification, disease emergence or shift in metabolic capabil...

  4. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder;

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... high frequency of loss of heterozygosity. The genes and ESTs presented in this study encode new potential tumor markers as well as potential novel therapeutic targets for prevention or therapy of CRC....

  5. Gene therapy in pancreatic cancer

    OpenAIRE

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-01-01

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC...

  6. Hormones, genes, and behavior

    OpenAIRE

    Pfaff, Donald W.

    1997-01-01

    With assays of hormone-sensitive behaviors, it is possible to demonstrate both direct and indirect actions of genes on mammalian social behaviors. Direct effects of estrogen receptor gene expression and progesterone receptor gene expression figure prominently in well analyzed neuroendocrine mechanisms for sex behavior, operating through a neural circuit that has been delineated. Indirect effects, notably the consequences of sexual differentiation, display complex d...

  7. Gene therapy for psychiatric disorders

    OpenAIRE

    Thome, Johannes; HÄSSLER, FRANK; ZACHARIOU, VANNA

    2011-01-01

    There is no indication that gene therapy can be applied in psychiatric patients any time soon. However, there are several promising developments on the level of experimental neuroscience indicating that gene therapy approaches have an effect in animal models of several psychiatric disorders including drug addiction, affective disorders, psychoses and dementia, modifying behavioural parameters via interventions on the molecular and cellular level. However, before gene therapy in psychiatric di...

  8. Combinatorial approaches to gene recognition.

    Science.gov (United States)

    Roytberg, M A; Astakhova, T V; Gelfand, M S

    1997-01-01

    Recognition of genes via exon assembly approaches leads naturally to the use of dynamic programming. We consider the general graph-theoretical formulation of the exon assembly problem and analyze in detail some specific variants: multicriterial optimization in the case of non-linear gene-scoring functions; context-dependent schemes for scoring exons and related procedures for exon filtering; and highly specific recognition of arbitrary gene segments, oligonucleotide probes and polymerase chain reaction (PCR) primers. PMID:9440930

  9. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic, the...... parameter and the genesis and distribution of the gene-level statistics, and illustrate the effects of differential weighting in a real-life example....

  10. Gene therapy for Parkinson's disease.

    Science.gov (United States)

    Lawlor, Patricia A; During, Matthew J

    2004-03-01

    Parkinson's disease (PD) is a debilitating neurodegenerative disorder arising from loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of striatal dopamine levels, which results in distressing motor symptoms. The current standard pharmacological treatment for PD is direct replacement of dopamine by treatment with its precursor, levodopa (L-dopa). However, this does not significantly alter disease progression and might contribute to the ongoing pathology. Several features of PD make this disease one of the most promising targets for clinical gene therapy of any neurological disease. The confinement of the major pathology to a compact, localised neuronal population and the anatomy of the basal ganglia circuitry mean that global gene transfer is not required and there are well-defined sites for gene transfer. The multifactorial aetiology of idiopathic PD means that it is unlikely any single gene will cure the disease, and as a result at least three separate gene-transfer strategies are currently being pursued: transfer of genes for enzymes involved in dopamine production; transfer of genes for growth factors involved in dopaminergic cell survival and regeneration; and transfer of genes to reset neuronal circuitry by switching cellular phenotype. The merits of these strategies are discussed here, along with remaining hurdles that might impede transfer of gene therapy technology to the clinic as a treatment for PD. PMID:15000692

  11. ERGDB: Estrogen Responsive Genes Database.

    Science.gov (United States)

    Tang, Suisheng; Han, Hao; Bajic, Vladimir B

    2004-01-01

    ERGDB is an integrated knowledge database dedicated to genes responsive to estrogen. Genes included in ERGDB are those whose expression levels are experimentally proven to be either up-regulated or down-regulated by estrogen. Genes included are identified based on publications from the PubMed database and each record has been manually examined, evaluated and selected for inclusion by biologists. ERGDB aims to be a unified gateway to store, search, retrieve and update information about estrogen responsive genes. Each record contains links to relevant databases, such as GenBank, LocusLink, Refseq, PubMed and ATCC. The unique feature of ERGDB is that it contains information on the dependence of gene reactions on experimental conditions. In addition to basic information about the genes, information for each record includes gene functional description, experimental methods used, tissue or cell type, gene reaction, estrogen exposure time and the summary of putative estrogen response elements if the gene's promoter sequence was available. Through a web interface at http://sdmc.i2r.a-star.edu.sg/ergdb/ cgi-bin/explore.pl users can either browse or query ERGDB. Access is free for academic and non-profit users. PMID:14681475

  12. Swimming Behavior Analysis Based on Bacterial Chemotaxis in Solution

    Institute of Scientific and Technical Information of China (English)

    Bin He; Zhipeng Wang; Chaoqun Liu; Yonggang Li; Runjie Shen

    2012-01-01

    Microrobots is playing more and more important roles for medical applications,such as targeting tumoral lesions for therapeutic purposes,Minimally Invasive Surgery (MIS) and highly localized drug delivery.However,energy efficient propulsion system poses significant challenges for the implementation of such mobile robots.Flagellated chemotactic bacteria can be used as an effective integrated propulsion system for microrobots.In this paper,we proposed a new type of propulsion method that is inspired by the motility mechanism of flagellated chemotactic bacteria in different pH gradients.The pH gradient field was established in solution through electrolysis method.The distribution of the pH values in solution was measured with pH indicator and analyzed with image processing technology,and the mechanism by which the pH values changed was also discussed.The swimming speed and direction of the bacteria were studied experimentally.Through analyzing the key parameters,such as stabilization time and electrode voltage,the optimal design of propulsion mechanism based on bacteria motion in the pH gradient field was proven.

  13. New method for exploring chemotaxis of mast cells

    Czech Academy of Sciences Publication Activity Database

    Hájková, Zuzana; Dráber, Pavel

    Vranovská Ves, 2014. [Cytoskeletal club 2014. 21.05.2014-23.5.2014, Vranovská Ves] R&D Projects: GA MŠk(CZ) LD13015 Institutional support: RVO:68378050 Subject RIV: EB - Genetics ; Molecular Biology

  14. A quasi-linear parabolic system of chemotaxis

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available We consider a quasi-linear parabolic system with respect to unknown functions u and v on a bounded domain of n -dimensional Euclidean space. We assume that the diffusion coefficient of u is a positive smooth function A ( u , and that the diffusion coefficient of v is a positive constant. If A ( u is a positive constant, the system is referred to as so-called Keller-Segel system. In the case where the domain is a bounded domain of two-dimensional Euclidean space, it is shown that some solutions to Keller-Segel system blow up in finite time. In three and more dimensional cases, it is shown that solutions to so-called Nagai system blow up in finite time. Nagai system is introduced by Nagai. The diffusion coefficients of Nagai system are positive constants. In this paper, we describe that solutions to the quasi-linear parabolic system exist globally in time, if the positive function A ( u rapidly increases with respect to u .

  15. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    Directory of Open Access Journals (Sweden)

    Ritankar Majumdar

    2016-01-01

    Full Text Available Leukotriene B4 (LTB4 is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments.

  16. Reaction Diffusion and Chemotaxis for Decentralized Gathering on FPGAs

    Directory of Open Access Journals (Sweden)

    Bernard Girau

    2009-01-01

    and rapid simulations of the complex dynamics of this reaction-diffusion model. Then we describe the FPGA implementation of the environment together with the agents, to study the major challenges that must be solved when designing a fast embedded implementation of the decentralized gathering model. We analyze the results according to the different goals of these hardware implementations.

  17. Chemotaxis in the Plasmodial Slime Mold, Physarum polycephalum.

    Science.gov (United States)

    Bozzone, Donna M.; Martin, Denise A.

    1998-01-01

    Describes a biology unit designed so that students pose their own questions and perform experiments to answer these questions. Plasmodial slime mold is employed as the focus of the study with background information about the mold provided. (DDR)

  18. Human Insulin Modulation of Escherichia coli Adherence and Chemotaxis

    Directory of Open Access Journals (Sweden)

    Karolina Klosowska

    2006-01-01

    Full Text Available Escherichia coli exhibited increased hydrophobicity and mannose-resistant epithelial cell adherence after growth in the presence of human insulin (2 µU mLˉ1 or 200 µUmLˉ1 insulin, respectively with glucose (100 mg dLˉ1. Capsule production and hemagglutination were unaffected by insulin and glucose. Chemotactic attraction to glucose as compared to insulin or glucose alone was enhanced by the presence of insulin. Insulin alone (200 µU mLˉ1 was a chemorepellent and inhibited flagellar tethering to glass. These findings indicate that human insulin can modulate E. coli’s expression of factors associated with pathogenesis in a manner that is modifiable by the presence of glucose.

  19. The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis

    OpenAIRE

    Wang, Fei

    2009-01-01

    Chemotaxis—the directed movement of cells in a gradient of chemoattractant—is essential for neutrophils to crawl to sites of inflammation and infection and for Dictyostelium discoideum (D. discoideum) to aggregate during morphogenesis. Chemoattractant-induced activation of spatially localized cellular signals causes cells to polarize and move toward the highest concentration of the chemoattractant. Extensive studies have been devoted to achieving a better understanding of the mechanism(s) use...

  20. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    Science.gov (United States)

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. PMID:26741884

  1. Emergent Collective Chemotaxis without Single-Cell Gradient Sensing

    Science.gov (United States)

    Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

    2016-03-01

    Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments show that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior is observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance," and study a model based on this mechanism both analytically and computationally. Our approach posits that contact inhibition of locomotion, where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how the cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.

  2. Chemotaxis of artificial microswimmers in active density waves.

    Science.gov (United States)

    Geiseler, Alexander; Hänggi, Peter; Marchesoni, Fabio; Mulhern, Colm; Savel'ev, Sergey

    2016-07-01

    Living microorganisms are capable of a tactic response to external stimuli by swimming toward or away from the stimulus source; they do so by adapting their tactic signal transduction pathways to the environment. Their self-motility thus allows them to swim against a traveling tactic wave, whereas a simple fore-rear asymmetry argument would suggest the opposite. Their biomimetic counterpart, the artificial microswimmers, also propel themselves by harvesting kinetic energy from an active medium, but, in contrast, lack the adaptive capacity. Here we investigate the transport of artificial swimmers subject to traveling active waves and show, by means of analytical and numerical methods, that self-propelled particles can actually diffuse in either direction with respect to the wave, depending on its speed and waveform. Moreover, chiral swimmers, which move along spiraling trajectories, may diffuse preferably in a direction perpendicular to the active wave. Such a variety of tactic responses is explained by the modulation of the swimmer's diffusion inside traveling active pulses. PMID:27575185

  3. On the theory of cell migration: durotaxis and chemotaxis

    OpenAIRE

    Diego Íñiguez, Javier

    2013-01-01

    Cell migration is a fundamental element in a variety of physiological and pathological processes. Alteration of its regulatory mechanisms leads to loss of adhesion and increased motility, critical steps in the initial stages of metastasis. Consequently, cell migration has become the focus of intensive experimental and theoretical studies; however the understanding many of its mechanisms remains elusive. Cell migration is the result of a periodic sequence of protrusion, adhesion remodeling and...

  4. A possible role of chemotaxis in germinal center formation

    CERN Document Server

    Beyer, T; Soff, G; Beyer, Tilo; Meyer-Hermann, Michael; Soff, Gerhard

    2002-01-01

    During the germinal center reaction a characteristic morphology is developed. In the framework of a recently developed space-time-model for the germinal center a mechanism for the formation of dark and light zones has been proposed. The mechanism is based on a diffusing differentiation signal which is secerned by follicular dendritic cells. Here, we investigate a possible influence of recently found chemokines for the germinal center formation in the framework of a single-cell-based stochastic and discrete three-dimensional model. We will also consider alternative possible chemotactic pathways that may play a role for the development of both zones. Our results suggest that the centrocyte motility resulting from a follicular dendritic cell-derived chemokine has to exceed a lower limit to allow the separation of centroblasts and centrocytes. In contrast to light microscopy the dark zone is ring shaped. This suggests that FDC-derived chemoattractants alone cannot explain the typical germinal center morphology.

  5. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

    Science.gov (United States)

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A.

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. PMID:26741884

  6. Circulation and chemotaxis of fetal hematopoietic stem cells.

    OpenAIRE

    Christensen, Julie L.; Wright, Douglas E.; Wagers, Amy J.; Weissman, Irving L.

    2004-01-01

    The major site of hematopoiesis transitions from the fetal liver to the spleen and bone marrow late in fetal development. To date, experiments have not been performed to evaluate functionally the migration and seeding of hematopoietic stem cells (HSCs) during this period in ontogeny. It has been proposed that developmentally timed waves of HSCs enter the bloodstream only during distinct windows to seed the newly forming hematopoietic organs. Using competitive reconstitution assays to measure ...

  7. Chemotaxis of artificial microswimmers in active density waves

    Science.gov (United States)

    Geiseler, Alexander; Hänggi, Peter; Marchesoni, Fabio; Mulhern, Colm; Savel'ev, Sergey

    2016-07-01

    Living microorganisms are capable of a tactic response to external stimuli by swimming toward or away from the stimulus source; they do so by adapting their tactic signal transduction pathways to the environment. Their self-motility thus allows them to swim against a traveling tactic wave, whereas a simple fore-rear asymmetry argument would suggest the opposite. Their biomimetic counterpart, the artificial microswimmers, also propel themselves by harvesting kinetic energy from an active medium, but, in contrast, lack the adaptive capacity. Here we investigate the transport of artificial swimmers subject to traveling active waves and show, by means of analytical and numerical methods, that self-propelled particles can actually diffuse in either direction with respect to the wave, depending on its speed and waveform. Moreover, chiral swimmers, which move along spiraling trajectories, may diffuse preferably in a direction perpendicular to the active wave. Such a variety of tactic responses is explained by the modulation of the swimmer's diffusion inside traveling active pulses.

  8. Nox2 Is Required for Macrophage Chemotaxis towards CSF-1

    OpenAIRE

    Sanjay Chaubey; Jones, Gareth E.; Shah, Ajay M.; Cave, Alison C.; Wells, Claire M.

    2013-01-01

    Macrophage migration and infiltration is an important first step in many pathophysiological processes, in particular inflammatory diseases. Redox modulation of the migratory signalling processes has been reported in endothelial cells, vascular smooth muscle cells and fibroblasts. However the redox modulation of the migratory process in macrophages and in particular that from the NADPH oxidase-2 (Nox2) dependent ROS has not been established. To investigate the potential role of Nox2 in the mig...

  9. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    OpenAIRE

    Ritankar Majumdar; Aidin Tavakoli Tameh; Carole A Parent

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4...

  10. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

    OpenAIRE

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Carole A Parent

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4...

  11. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata;

    2015-01-01

    expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles for these...

  12. LSL_(gene) - Wikipedia, the free encyclopedia [Gene Wiki

    Lifescience Database Archive (English)

    Full Text Available LSL (gene) - Wikipedia, the free encyclopediaLSL (gene)From Wikipedia, the free encyclopediaJump ... n-bound leptin from subcutaneous adipose tissue of lean ... and obese women". J. Clin. Endocrinol. Metab. 87 ( ... et al. (2003). "Serum leptin activity in obese and lean ... patients". Regul. Pept. 111 (1–3): 77–82. doi:10.1 ...

  13. BBX_(gene) - Wikipedia, the free encyclopedia [Gene Wiki

    Lifescience Database Archive (English)

    Full Text Available BBX (gene) - Wikipedia, the free encyclopediaBBX (gene)From Wikipedia, the free encyclopediaJump ... of disease to interested scientists.[12][13][14]Male an d female an imals underwent a standardized phenotyp ... while mutants of both sexes showed a reduction in lean ... body mass. Radiography found that males had abnorm ...

  14. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    Gregersen, Noomi O; Buttenschøn, Henriette Nørmølle; Hedemand, Anne;

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12, a...

  15. STATE-OF-THE-ART HUMAN GENE THERAPY: PART I. GENE DELIVERY TECHNOLOGIES

    OpenAIRE

    Wang, Dan; Gao, Guangping

    2014-01-01

    Safe and effective gene delivery is a prerequisite for successful gene therapy. In the early age of human gene therapy, setbacks due to problematic gene delivery vehicles plagued the exciting therapeutic outcome. However, gene delivery technologies rapidly evolved ever since. With the advancement of gene delivery techniques, gene therapy clinical trials surged during the past decade. As the first gene therapy product has obtained regulatory approval and reached clinic, human gene therapy fina...

  16. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas

    2010-05-01

    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  17. Small molecule antagonism of oxysterol-induced Epstein-Barr virus induced gene 2 (EBI2) activation

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Madsen, Christian M; Arfelt, Kristine N;

    2013-01-01

    682753A, which blocks oxysterol-induced G-protein activation, β-arrestin recruitment and B-cell chemotaxis. We furthermore demonstrate that activation triggers pertussis toxin-sensitive MAP kinase phosphorylation, which is also inhibited by GSK682753A. Thus, EBI2 signalling in B cells mediates key...

  18. Advancement and prospects of tumor gene therapy

    OpenAIRE

    Zhang, Chao; Wang, Qing-Tao; Liu, He; Zhang, Zhen-Zhu; Huang, Wen-Lin

    2011-01-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA inter...

  19. Evidence Based Selection of Housekeeping Genes

    OpenAIRE

    de Jonge, Hendrik J.M.; Fehrmann, Rudolf S. N.; Eveline S. J. M. de Bont; Hofstra, Robert M. W.; Gerbens, Frans; Kamps, Willem A.; Vries, Elisabeth G. E.; van der Zee, Ate G.J.; te Meerman, Gerard J.; ter Elst, Arja

    2007-01-01

    For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes (reference or internal control genes) is required. It is known that commonly used housekeeping genes (e.g. ACTB, GAPDH, HPRT1, and B2M) vary considerably under different experimental conditions and therefore their use for normalization is limited. We performed a meta-analysis of 13,629 human gene array samples in order to identify the most stable expressed genes. Here we show n...

  20. A Combinatorial Approach to Detecting Gene-Gene and Gene-Environment Interactions in Family Studies

    OpenAIRE

    Lou, Xiang-Yang; Chen, Guo-Bo; Yan, Lei; Ma, Jennie Z.; Mangold, Jamie E.; Zhu, Jun; Elston, Robert C.; Li, Ming D.

    2008-01-01

    Widespread multifactor interactions present a significant challenge in determining risk factors of complex diseases. Several combinatorial approaches, such as the multifactor dimensionality reduction (MDR) method, have emerged as a promising tool for better detecting gene-gene (G × G) and gene-environment (G × E) interactions. We recently developed a general combinatorial approach, namely the generalized multifactor dimensionality reduction (GMDR) method, which can entertain both qualitative ...

  1. Gene-Gene and Gene-Environment Interactions in Ulcerative Colitis

    OpenAIRE

    Wang, Ming-Hsi; FIOCCHI, CLAUDIO; Zhu, Xiaofeng; Ripke, Stephan; Kamboh, M. Ilyas; Rebert, Nancy; Duerr, Richard H.; Achkar, Jean-Paul

    2013-01-01

    Genome-wide association studies (GWAS) have identified at least 133 ulcerative colitis (UC) associated loci. The role of genetic factors in clinical practice is not clearly defined. The relevance of genetic variants to disease pathogenesis is still uncertain because of not characterized gene-gene and gene-environment interactions. We examined the predictive value of combining the 133 UC risk loci with genetic interactions in an ongoing inflammatory bowel disease (IBD) GWAS. The Wellcome Trust...

  2. Candidate genes for behavioural ecology

    NARCIS (Netherlands)

    Fitzpatrick, M.J.; Ben-Sahar, Y.; Smid, H.M.; Vet, L.E.M.; Robinson, G.E.; Sokolowski, M.B.

    2005-01-01

    In spite of millions of years of evolutionary divergence, the conservation of gene function is common across distant lineages. As such, genes that are known to influence behaviour in one organism are likely to influence similar behaviours in other organisms. Recent studies of the evolution of behavi

  3. HOX genes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kelly Zoë L

    2011-09-01

    Full Text Available Abstract The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development. Here we review a number of recent studies showing that HOX genes are strongly expressed in ovarian cancer, and that in some cases the expression of specific HOX genes is sufficient to confer a particular identity and phenotype upon cancer cells. We also review the recent advances in elucidating the different functions of HOX genes in ovarian cancer. A literature search was performed using the search terms HOX genes (including specific HOX genes, ovarian cancer and oncogenesis. Articles were accessed through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect. Taken together, these studies have shown that HOX genes play a role in the oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA repair and enhanced cell motility. The function of HOX genes in ovarian cancer oncogenesis supports their potential role as prognostic and diagnostic markers, and as therapeutic targets in this disease.

  4. Candidate gene prioritization with Endeavour.

    Science.gov (United States)

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-01

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/. PMID:27131783

  5. On meme--gene coevolution.

    Science.gov (United States)

    Bull, L; Holland, O; Blackmore, S

    2000-01-01

    In this article we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability. PMID:11224917

  6. Phytochrome-regulated Gene Expression

    Institute of Scientific and Technical Information of China (English)

    Peter H. Quail

    2007-01-01

    Identification of all genes involved in the phytochrome (phy)-mediated responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth and development. This article highlights and integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-regulated genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an initial subset of these genes. The data: (a) reveal considerable complexity in the channeling of the light signals through the different phy-family members (phyA to phyE) to responsive genes; (b) identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, and, therefore, as potentially important regulators in the transcriptional-network hierarchy; and (c) identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetiolation.

  7. Multifunctional nanorods for gene delivery

    Science.gov (United States)

    Salem, Aliasger K.; Searson, Peter C.; Leong, Kam W.

    2003-10-01

    The goal of gene therapy is to introduce foreign genes into somatic cells to supplement defective genes or provide additional biological functions, and can be achieved using either viral or synthetic non-viral delivery systems. Compared with viral vectors, synthetic gene-delivery systems, such as liposomes and polymers, offer several advantages including ease of production and reduced risk of cytotoxicity and immunogenicity, but their use has been limited by the relatively low transfection efficiency. This problem mainly stems from the difficulty in controlling their properties at the nanoscale. Synthetic inorganic gene carriers have received limited attention in the gene-therapy community, the only notable example being gold nanoparticles with surface-immobilized DNA applied to intradermal genetic immunization by particle bombardment. Here we present a non-viral gene-delivery system based on multisegment bimetallic nanorods that can simultaneously bind compacted DNA plasmids and targeting ligands in a spatially defined manner. This approach allows precise control of composition, size and multifunctionality of the gene-delivery system. Transfection experiments performed in vitro and in vivo provide promising results that suggest potential in genetic vaccination applications.

  8. FunGeneClusterS

    DEFF Research Database (Denmark)

    Vesth, Tammi Camilla; Brandl, Julian; Andersen, Mikael Rørdam

    2016-01-01

    Secondary metabolites of fungi are receiving an increasing amount of interest due to their prolific bioactivities and the fact that fungal biosynthesis of secondary metabolites often occurs from co-regulated and co-located gene clusters. This makes the gene clusters attractive for synthetic biology...

  9. Coupling the phosphotransferase system and the methyl-accepting chemotaxis protein-dependent chemotaxis signaling pathways of Escherichia coli.

    OpenAIRE

    Lux, R.; Jahreis, K; Bettenbrock, K.; Parkinson, J S; Lengeler, J W

    1995-01-01

    Chemotactic responses in Escherichia coli are typically mediated by transmembrane receptors that monitor chemoeffector levels with periplasmic binding domains and communicate with the flagellar motors through two cytoplasmic proteins, CheA and CheY. CheA autophosphorylates and then donates its phosphate to CheY, which in turn controls flagellar rotation. E. coli also exhibits chemotactic responses to substrates that are transported by the phosphoenolpyruvate (PEP)-dependent carbohydrate phosp...

  10. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  11. CNS Genes Implicated in Relapse

    Directory of Open Access Journals (Sweden)

    Willard M. Freeman

    2008-01-01

    Full Text Available Drug abuse is a condition that impacts not only the individual drug user, but society as a whole. Although prevention of initial drug use is the most effective way to prevent addiction, avoiding relapse is a crucial component of drug addiction recovery. Recent studies suggest that there is a set of genes whose expression is robustly and stably altered following drug use and ensuing abstinence. Such stable changes in gene expression correlate with ultrastructural changes in brain as well as alterations in behavior. As persistent molecular changes, these genes may provide targets for the development of therapeutics. Developing a list of well-characterized candidate genes and examining the effect of manipulating these genes will contribute to the ultimate goal of developing effective treatments to prevent relapse to drug use.

  12. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used to...... describe different aspects of molecular biology of the cell, to study changes that occur in the cell due to overexpression or deletion of a gene and to identify various protein modifications. The biological questions and the results of the described studies show the diversity of the information that can be...... characterising yeast genes and proteins. It reports the first global proteome database collecting 36 yeast single gene deletion mutants and selecting over 650 differences between analysed mutants and the wild type strain. The obtained results show that two-dimensional gel electrophoresis and mass spectrometry...

  13. GeneMANIA Prediction Server 2013 Update

    OpenAIRE

    Zuberi, Khalid; Franz, Max; Rodriguez, Harold; Montojo, Jason; Lopes, Christian Tannus; Bader, Gary D.; Morris, Quaid

    2013-01-01

    GeneMANIA (http://www.genemania.org) is a flexible user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. GeneMANIA can also be used in a function predict...

  14. Gene expression profiling: can we identify the right target genes?

    Directory of Open Access Journals (Sweden)

    J. E. Loyd

    2008-12-01

    Full Text Available Gene expression profiling allows the simultaneous monitoring of the transcriptional behaviour of thousands of genes, which may potentially be involved in disease development. Several studies have been performed in idiopathic pulmonary fibrosis (IPF, which aim to define genetic links to the disease in an attempt to improve the current understanding of the underlying pathogenesis of the disease and target pathways for intervention. Expression profiling has shown a clear difference in gene expression between IPF and normal lung tissue, and has identified a wide range of candidate genes, including those known to encode for proteins involved in extracellular matrix formation and degradation, growth factors and chemokines. Recently, familial pulmonary fibrosis cohorts have been examined in an attempt to detect specific genetic mutations associated with IPF. To date, these studies have identified families in which IPF is associated with mutations in the gene encoding surfactant protein C, or with mutations in genes encoding components of telomerase. Although rare and clearly not responsible for the disease in all individuals, the nature of these mutations highlight the importance of the alveolar epithelium in disease pathogenesis and demonstrate the potential for gene expression profiling in helping to advance the current understanding of idiopathic pulmonary fibrosis.

  15. Genes and gene networks implicated in aggression related behaviour.

    Science.gov (United States)

    Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

    2014-10-01

    Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour. PMID:25142712

  16. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  17. Genes and equality.

    Science.gov (United States)

    Farrelly, C

    2004-12-01

    The way people think about equality as a value will influence how they think genetic interventions should be regulated. In this paper the author uses the taxonomy of equality put forth by Derek Parfit and applies this to the issue of genetic interventions. It is argued that telic egalitarianism is untenable and that deontic egalitarianism collapses into prioritarianism. The priority view maintains that it is morally more important to benefit the people who are worse off. Once this precision has been given to the concerns egalitarians have, a number of diverse issues must be considered before determining what the just regulation of genetic interventions would be. Consideration must be given to the current situation of the least advantaged, the fiscal realities behind genetic interventions, the budget constraints on other social programmes egalitarians believe should receive scarce public funds, and the interconnected nature of genetic information. These considerations might lead egalitarians to abandon what they take to be the obvious policy recommendations for them to endorse regarding the regulation of gene therapies and enhancements. PMID:15574450

  18. Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

    OpenAIRE

    McDonald Karen; Jung Sang-Kyu

    2011-01-01

    Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interfac...

  19. GeneNet: a database on structure and functional organisation of gene networks

    OpenAIRE

    Ananko, E A; Podkolodny, N. L.; Stepanenko, I. L.; Ignatieva, E. V.; Podkolodnaya, O. A.; Kolchanov, N. A.

    2002-01-01

    The GeneNet database is designed for accumulation of information on gene networks. Original technology applied in GeneNet enables description of not only a gene network structure and functional relationships between components, but also metabolic and signal transduction pathways. Specialised software, GeneNet Viewer, automatically displays the graphical diagram of gene networks described in the database. Current release 3.0 of GeneNet database contains descriptions of 25 gene networks, 945 pr...

  20. Genes: an Open Access Journal

    Directory of Open Access Journals (Sweden)

    J. Peter W. Young

    2009-11-01

    Full Text Available Genes have been in the scientific vocabulary for a hundred years. The term "gene" was proposed by the Danish plant scientist Wilhelm Johannsen in the first decade of the 20th century. For Johannsen, the gene remained an abstract concept, "free of any hypothesis" [1], but others were already pointing to chromosomes as the likely location of genes. The science of genetics was born at that time, and genes were rapidly connected with mutations, with patterns of inheritance, with development, with quantitative traits, with evolution and with biochemical pathways. All this was achieved without knowledge of the physical nature of genes, but this changed in mid-century with the discoveries of molecular biology. DNA was revealed as the genetic material, and the mechanisms were elucidated by which the information was encoded, and propagated, and linked to the phenotype. However, the concept of a "gene" did not become clearer. Quite the reverse, as the units of mutation, of recombination, of inheritance, of expression, of regulation, etc. did not necessarily coincide. [...

  1. Gene Electrotransfer: A Mechanistic Perspective.

    Science.gov (United States)

    Rosazza, Christelle; Meglic, Sasa Haberl; Zumbusch, Andreas; Rols, Marie-Pierre; Miklavcic, Damijan

    2016-01-01

    Gene electrotransfer is a powerful method of DNA delivery offering several medical applications, among the most promising of which are DNA vaccination and gene therapy for cancer treatment. Electroporation entails the application of electric fields to cells which then experience a local and transient change of membrane permeability. Although gene electrotransfer has been extensively studied in in vitro and in vivo environments, the mechanisms by which DNA enters and navigates through cells are not fully understood. Here we present a comprehensive review of the body of knowledge concerning gene electrotransfer that has been accumulated over the last three decades. For that purpose, after briefly reviewing the medical applications that gene electrotransfer can provide, we outline membrane electropermeabilization, a key process for the delivery of DNA and smaller molecules. Since gene electrotransfer is a multipart process, we proceed our review in describing step by step our current understanding, with particular emphasis on DNA internalization and intracellular trafficking. Finally, we turn our attention to in vivo testing and methodology for gene electrotransfer. PMID:27029943

  2. The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing

    DEFF Research Database (Denmark)

    Theilgaard-Monch, K.; Knudsen, Steen; Follin, P.; Borregaard, N.

    2004-01-01

    of PMNs. Among the up-regulated genes were cytokines and chemokines critical for chemotaxis of macrophages, T cells, and PMNs, and for the modulation of their inflammatory responses. PMNs in skin lesions down-regulated receptors mediating chemotaxis and anti-microbial activity, but up-regulated other...

  3. Gene expression profiles in skeletal muscle after gene electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille; Zibert, John R; Gissel, Hanne;

    2007-01-01

    BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... therefore investigated transcriptional changes through gene expression profile analyses, morphological changes by histological analysis, and physiological changes by force generation measurements. DNA electrotransfer was obtained using a combination of a short high voltage pulse (HV, 1000 V/cm, 100 mus......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

  4. BRCA1 and BRCA2 gene testing

    Science.gov (United States)

    The BRCA1 and BRCA2 gene test is a blood test that can tell you if you have a higher ... BRCA1 and BRCA2 are genes that suppress malignant tumors (cancer) in humans. When these genes change (become ...

  5. Gene Therapy for Diseases and Genetic Disorders

    Science.gov (United States)

    ... Mentor Submit Your Press Release Donate Home ASGCT Gene Therapy for Diseases Gene Therapy has made important ... Among the most notable advancements are the following: Gene Therapy for Genetic Disorders Severe Combined Immune Deficiency ( ...

  6. Genes Might Explain Hispanics' Added Longevity

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160528.html Genes Might Explain Hispanics' Added Longevity Differences in 'genetic ... Services, or federal policy. More Health News on: Genes and Gene Therapy Hispanic American Health Recent Health ...

  7. Personalized Medicine: Matching Treatments to Your Genes

    Science.gov (United States)

    ... disclaimer . Subscribe Personalized Medicine Matching Treatments to Your Genes You’re one of a kind. It’s not ... personalized medicine begins with the unique set of genes you inherited from your parents. Genes are stretches ...

  8. Basics on Genes and Genetic Disorders

    Science.gov (United States)

    ... Help a Friend Who Cuts? The Basics on Genes and Genetic Disorders KidsHealth > For Teens > The Basics ... such as treating health problems. What Is a Gene? To understand how genes work, let's review some ...

  9. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin;

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies. For...... maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce an...

  10. Gene networks controlling petal organogenesis.

    Science.gov (United States)

    Huang, Tengbo; Irish, Vivian F

    2016-01-01

    One of the biggest unanswered questions in developmental biology is how growth is controlled. Petals are an excellent organ system for investigating growth control in plants: petals are dispensable, have a simple structure, and are largely refractory to environmental perturbations that can alter their size and shape. In recent studies, a number of genes controlling petal growth have been identified. The overall picture of how such genes function in petal organogenesis is beginning to be elucidated. This review will focus on studies using petals as a model system to explore the underlying gene networks that control organ initiation, growth, and final organ morphology. PMID:26428062

  11. The Ensembl gene annotation system.

    Science.gov (United States)

    Aken, Bronwen L; Ayling, Sarah; Barrell, Daniel; Clarke, Laura; Curwen, Valery; Fairley, Susan; Fernandez Banet, Julio; Billis, Konstantinos; García Girón, Carlos; Hourlier, Thibaut; Howe, Kevin; Kähäri, Andreas; Kokocinski, Felix; Martin, Fergal J; Murphy, Daniel N; Nag, Rishi; Ruffier, Magali; Schuster, Michael; Tang, Y Amy; Vogel, Jan-Hinnerk; White, Simon; Zadissa, Amonida; Flicek, Paul; Searle, Stephen M J

    2016-01-01

    The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail.Database URL: http://www.ensembl.org/index.html. PMID:27337980

  12. 幽门螺杆菌cheA和cheY基因表达及其产物与细菌趋化的相关性%Prokaryotic expression of Helicobacter pylori cheA and cheY genes and correlation among the expressed products and bacterial chemotactic behavior

    Institute of Scientific and Technical Information of China (English)

    吴盛海; 徐丽慧; 严杰; 王贤军

    2009-01-01

    目的 克隆幽门螺杆菌趋化相关基因cheA和they并构建其原核表达系统,建立幽门螺杆菌体外趋化模型并确定其趋化诱导物质,了解特异性抗体和氯氰碘柳胺对幽门螺杆菌趋化的抑制作用.方法 PCR扩增幽门螺杆菌NCTC11637株全长cheA和cheY基因片段,T-A克隆后测序.构建上述目的基因原核表达系统,采用SDS-PAGE和Bio-Rad凝胶成像分析系统检查目的重组蛋白rCheA和rCheY的表达情况,Ni-NTA亲和层析法提纯rCheA和rCheY.rCheA和rCheY免疫家兔获得抗血清,用饱和硫酸铵沉淀法和DEAE-32离子交换法提纯IsG,用免疫扩散法检测抗血清及其IsG效价.采用硬琼脂法建立幽门螺杆菌NCTC11637株体外趋化模型并检测11种物质的趋化诱导作用,同时分别观察抗rCheA IgG(rCheA-IgG)和氯氰碘柳胺钠对细菌趋化的抑制作用.结果 PCR扩增获得预期大小的cheA和cheY基因片段,其核苷酸和氨基酸序列与文献报道完全相同.所构建的原核表达系统能有效表达rCheA和rGheY.rCheA和rCheY兔抗血清及其IgG免疫扩散效价均分别为1:4和1:2.盐酸、硫酸和乙酸对该幽门螺杆菌均有趋化诱导作用,一定浓度的rCheA-IgG和氯氰碘柳胺钠均对幽门螺杆菌趋化有抑制作用(P<0.05).结论 本研究成功地构建了幽门螺杆菌NCTC11637株cheA和cheY基因原核表达系统.H~+是诱导幽门螺杆菌趋化的信号物质,rCheA-IgG和氯氰碘柳胺钠均能抑制幽门螺杆菌对H~+的趋化.%Objective To clone the cheA and cheY genes of Helicobacter pylori for construction of their prokaryotic expression systems, and to establish chemotactic model in vitro of H. pylori for determing chemotaxis-inducing substances and to understand the effects of specific antibody and closantel on inhibiting chemotactic behavior of the microbe. Methods The segments of entire cheA and cheY genes were amplified by PGR and then sequenced after T-A cloning. Prokaryotic expression systems of the

  13. A Gene Score Test for Disease Association with Multiple Genes

    OpenAIRE

    Changchun Xie

    2011-01-01

    The traditional method for creating a gene score to predict a given outcome is to use the most statistically significant single nucleotide polymorphisms (SNPs) from all SNPs which were tested. There are several disadvantages of this approach such as excluding SNPs that do not have strong single effects when tested on their own but do have strong joint effects when tested together with other SNPs. The interpretation of results from the traditional gene score may lack biological insight since t...

  14. Gene therapy of cancer by vaccines carrying inserted immunostimulatory genes

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2007-01-01

    Roč. 53, č. 3 (2007), s. 71-73. ISSN 0015-5500 Grant ostatní: EU-FP6 NoE Clinigene(XE) 018933; Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : gene therapy * immunostimulatory genes * vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.596, year: 2007

  15. Parsimonious selection of useful genes in microarray gene expression data

    OpenAIRE

    González Navarro, Félix Fernando; Belanche Muñoz, Luis Antonio

    2011-01-01

    Machine Learning methods have of late made significant efforts to solving multidisciplinary problems in the field of cancer classification in microarray gene expression data. These tasks are characterized by a large number of features and a few observations, making the modeling a non-trivial undertaking. In this work we apply entropic filter methods for gene selection, in combination with several off-the-shelf classifiers. The introduction of bootstrap resampling techniques permits the achiev...

  16. Expression of Green Fluorescent Protein Gene in Gluconacetobacter xylinus%绿色荧光蛋白基因在木葡糖酸醋杆菌中的表达

    Institute of Scientific and Technical Information of China (English)

    钟成; 刘淼; 李晶; 韩培培; 谭之磊; 贾士儒

    2015-01-01

    Green fluorescent protein(GFP)as a reporter protein is widely used in signal conduction and gene expression and regulation in microbiology. In this research,GFPgenes were successfully expressed inGluconacetobacter xylinus with shut-tle plasmid pMV24. GFP genes were cloned from pMUTIN-gfp+ plasmid and connected to pMV24 to build prokaryotic ex-pression plasmid pMV24-gfp+. Electrotransformation was applied to introduce pMV24-gfp+ intoG. xylinus. The transformant exhibits bright green fluorescence when exposed to blue light in the ultraviolet range of fluorescence microscope. It can pro-vide very important theoretical basis for the observation of cell movement and the analysis of kinesin ofG. xylinus under chemotaxis.%绿色荧光蛋白(green fluorescent protein,GFP)广泛应用于报告基因、基因的表达与调控以及微生物信号传导.以pMV24穿梭质粒为载体,实现了GFP在木葡糖酸醋杆菌(Gluconacetobacter xylinus)中的成功表达.采用PCR技术扩增出绿色荧光蛋白基因,连接至木葡糖酸醋杆菌表达载体 pMV24 中,构建成功的质粒命名为 pMV24-gfp+.采用电转化技术将重组载体导入木葡糖酸醋杆菌中,转化子在荧光显微镜的蓝色激发光下发出绿色荧光,为木葡糖酸醋杆菌趋化性的观察及菌体中运动蛋白的分析提供了重要的理论依据.

  17. Viral vectors for vascular gene therapy

    OpenAIRE

    Fischer, Lukas; Preis, Meir; Weisz, Anat; Koren, Belly; Lewis, Basil S; Flugelman, Moshe Y

    2002-01-01

    Vascular gene therapy is the focus of multiple experimental and clinical research efforts. While several genes with therapeutic potential have been identified, the best method of gene delivery is unknown. Viral vectors have the capacity to transfer genes at high efficiency rates. Several viral-based vectors have been used in experimental vascular gene therapy for in vivo and ex vivo gene transfer. Adenoviral-based vectors are being used for the induction of angiogenesis in phase 1 and 2 clini...

  18. Vector development for suicide gene therapy

    OpenAIRE

    Aints, Alar

    2002-01-01

    Gene therapy is used to treat conditions that arise from errors in the genetic makeup of cells either congenital diseases resulting from a deletion or mutation in a gene or malignant diseases where genetic regulation mechanisms have been deranged. Suicide gene therapy is one of several gene therapeutic approaches to treat cancer. A suicide gene is a gene encoding a protein, frequently an enzyme, that in itself is non-toxic to the genetically modified cell. However, when ...

  19. Evolution of the nuclear receptor gene superfamily.

    OpenAIRE

    Laudet, V; Hänni, C; Coll, J.; F. Catzeflis; Stéhelin, D

    1992-01-01

    Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dimerization (E domain). It is not known whether these genes have evolved through gene duplica...

  20. Evolution of alternative splicing after gene duplication

    OpenAIRE

    Su, Zhixi; Wang, Jianmin; Yu, Jun; Huang, Xiaoqiu; Gu, Xun

    2006-01-01

    Alternative splicing and gene duplication are two major sources of proteomic function diversity. Here, we study the evolutionary trend of alternative splicing after gene duplication by analyzing the alternative splicing differences between duplicate genes. We observed that duplicate genes have fewer alternative splice (AS) forms than single-copy genes, and that a negative correlation exists between the mean number of AS forms and the gene family size. Interestingly, we found that the loss of ...