Urease Plays an Important Role in the Chemotactic Motility of Helicobacter pylori in a Viscous Environment

PubMed Central

Nakamura, Hiroki; Yoshiyama, Hironori; Takeuchi, Hiroaki; Mizote, Tomoko; Okita, Kiwamu; Nakazawa, Teruko

1998-01-01

Helicobacter pylori exhibits chemotactic responses to urea, flurofamide, acetohydroxamic acid, and sodium bicarbonate. In buffer, the chemotactic activities of a urease-positive strain were higher than those of the isogenic urease-negative strain. Moreover, the chemotactic activities of the urease-positive strain were increased in a viscous solution containing 3% polyvinylpyrrolidone, whereas those of the urease-negative mutant were not. These results are in accordance with the fact that the mutant strain did not show swarming in motility agar regardless of having flagella. Incubation of the wild-type strain with flurofamide resulted in partial inhibition of the chemotactic activities in the viscous solution. In addition, incubation with acetohydroxamic acid, a low-molecular-weight, diffusible urease inhibitor, resulted in complete loss of chemotactic activity in the viscous solution. The inhibition of the chemotactic activity by urease inhibitors paralleled the inhibition of urease. The chemotactic activity of H. pylori was also inhibited by the proton carrier carbonyl cyanide m-chlorophenylhydrazone, showing that H. pylori utilizes proton motive force for motility. These results indicate that cytoplasmic urease plays an important role in the chemotactic motility of H. pylori under a condition that mimics the ecological niche of the bacterium, the gastric mucous layer. PMID:9746586

Urease plays an important role in the chemotactic motility of Helicobacter pylori in a viscous environment.

PubMed

Nakamura, H; Yoshiyama, H; Takeuchi, H; Mizote, T; Okita, K; Nakazawa, T

1998-10-01

Helicobacter pylori exhibits chemotactic responses to urea, flurofamide, acetohydroxamic acid, and sodium bicarbonate. In buffer, the chemotactic activities of a urease-positive strain were higher than those of the isogenic urease-negative strain. Moreover, the chemotactic activities of the urease-positive strain were increased in a viscous solution containing 3% polyvinylpyrrolidone, whereas those of the urease-negative mutant were not. These results are in accordance with the fact that the mutant strain did not show swarming in motility agar regardless of having flagella. Incubation of the wild-type strain with flurofamide resulted in partial inhibition of the chemotactic activities in the viscous solution. In addition, incubation with acetohydroxamic acid, a low-molecular-weight, diffusible urease inhibitor, resulted in complete loss of chemotactic activity in the viscous solution. The inhibition of the chemotactic activity by urease inhibitors paralleled the inhibition of urease. The chemotactic activity of H. pylori was also inhibited by the proton carrier carbonyl cyanide m-chlorophenylhydrazone, showing that H. pylori utilizes proton motive force for motility. These results indicate that cytoplasmic urease plays an important role in the chemotactic motility of H. pylori under a condition that mimics the ecological niche of the bacterium, the gastric mucous layer.

Chemotaxis of basophils by lymphocyte-dependent and lymphocyte-independent mechanisms.

PubMed

Ward, P A; Dvorak, H F; Cohen, S; Yoshida, T; Data, R; Selvaggio, S S

1975-05-01

Guine pigs basophils obtained from blood or bone marrow have been studied for their chemotactic responsiveness. Chemotactic factors for basophils include a substance (lymphokine) present in culture fluids from antigen-stimulated lymphocytes, a material generated in zymosan-activated guinea pig serum, a C5 cleavage factor, and a bacterial factor. When compared with homologous neutrophils and monocytes, basophils respond most rapidly to a chemotactic stimulus. The lymphokine basophil chemotactic factor is physicochemically similar to the previously described monocyte chemotactic factor but appears to be distinct from it as well as MIF and neutrophil chemotactic factor present in the same fluids, Part of the evidence for this is the ability to detect basophil chemotactic factor in the absence of other lymphokine activities under appropriate experimental conditions. More evidence, specifically relating to the monocyte factor, is that monocytes can adsorb basophil chemotactic activity but not vice versa. This latter observation may have implications for the mechanism whereby the accumulation of basophils is controlled and limited in vivo. In addition, it was noted that specific antigen could also suppress basophil chemotaxis. Although the mechanism of this phenomenon is unclear, it could serve as a second means by which basophil accumulation may be controlled in the intact animal. Taken together, these observations provide further definition of the chemotactic behavior of basophils in general, and underscore some of the ways in which lymphocytes can influence basophils through lymphokine-dependent mechanisms.

Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function

PubMed Central

Cardenas, Horacio; Arango, Daniel; Nicholas, Courtney; Duarte, Silvia; Nuovo, Gerard J.; He, Wei; Voss, Oliver H.; Gonzalez-Mejia, M. Elba; Guttridge, Denis C.; Grotewold, Erich; Doseff, Andrea I.

2016-01-01

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors’ accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo. PMID:26938530

Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

PubMed

Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

2017-12-01

Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

Human sperm pattern of movement during chemotactic re-orientation towards a progesterone source

PubMed Central

Blengini, Cecilia Soledad; Teves, Maria Eugenia; Uñates, Diego Rafael; Guidobaldi, Héctor Alejandro; Gatica, Laura Virginia; Giojalas, Laura Cecilia

2011-01-01

Human spermatozoa may chemotactically find out the egg by following an increasing gradient of attractant molecules. Although human spermatozoa have been observed to show several of the physiological characteristics of chemotaxis, the chemotactic pattern of movement has not been easy to describe. However, it is apparent that chemotactic cells may be identified while returning to the attractant source. This study characterizes the pattern of movement of human spermatozoa during chemotactic re-orientation towards a progesterone source, which is a physiological attractant candidate. By means of videomicroscopy and image analysis, a chemotactic pattern of movement was identified as the spermatozoon returned towards the source of a chemotactic concentration of progesterone (10 pmol l−1). First, as a continuation of its original path, the spermatozoon swims away from the progesterone source with linear movement and then turns back with a transitional movement that can be characterized by an increased velocity and decreased linearity. This sperm behaviour may help the spermatozoon to re-orient itself towards a progesterone source and may be used to identify the few cells that are undergoing chemotaxis at a given time. PMID:21765441

Identification of CtpL as a chromosomally encoded chemoreceptor for 4-chloroaniline and catechol in Pseudomonas aeruginosa PAO1.

PubMed

Vangnai, Alisa S; Takeuchi, Kazuki; Oku, Shota; Kataoka, Naoya; Nitisakulkan, Tisana; Tajima, Takahisa; Kato, Junichi

2013-12-01

Bacterial chemotaxis influences the ability of bacteria to survive and thrive in most environments, including polluted ones. Despite numerous reports of the phenotypic characterization of chemotactic bacteria, only a few molecular details of chemoreceptors for aromatic pollutants have been described. In this study, the molecular basis of chemotaxis toward an environmentally toxic chlorinated aromatic pollutant, 4-chloroaniline (4CA), was evaluated. Among the three Pseudomonas spp. tested, Pseudomonas aeruginosa PAO1 exhibited positive chemotaxis both to the nonmetabolizable 4CA, where 4-chloroacetanilide was formed as a dead-end transformation product, and to the metabolizable catechol. Molecular analysis of all 26 mutants with a disrupted methyl-accepting chemotaxis gene revealed that CtpL, a chromosomally encoded chemoreceptor, was responsible for the positive chemotactic response toward 4CA. Since CtpL has previously been described to be a major chemoreceptor for inorganic phosphate at low concentrations in PAO1, this report describes a fortuitous ability of CtpL to function toward aromatic pollutants. In addition, its regulation not only was dependent on the presence of the chemoattractant inducer but also was regulated by conditions of phosphate starvation. These results expand the range of known chemotactic transducers and their function in the environmental bacterium PAO1.

Expression of EMAP-II in the rat dental follicle and its potential role in tooth eruption

PubMed Central

Liu, Dawen; Wise, Gary E.

2008-01-01

Endothelial monocyte-activating polypeptide II (EMAP-II) is an inflammatory cytokine with chemotactic activity. Because the dental follicle (DF) recruits mononuclear cells (osteoclast precursors) to promote the osteoclastogenesis needed for tooth eruption, it was the aim of this study to determine if EMAP-II may contribute to this recruitment. Using a DNA microarray, EMAP-II was found to be highly expressed in vivo in the DFs of day 1 to day 11 postnatal rats, with its expression elevated at days 1 and 3. Using a siRNA to knock down EMAP-II expression also resulted in a reduction in expression of CSF-1 and MCP-1 in the DF cells. Addition of EMAP-II protein to the DF cells partially restored the expression of CSF-1 and MCP-1. In chemotaxis assays using either conditioned medium of the DF cells with anti-EMAP-II antibody added or conditioned medium of DF cells with EMAP-II knocked down by siRNA, migration indexes of bone marrow mononuclear cells were significantly reduced. These results suggest that EMAP-II is another chemotactic molecule in the dental follicle involved in recruitment of mononuclear cells, and that EMAP-II may exert its chemotactic function directly by recruiting mononuclear cells and indirectly by enhancing the expression of other chemotactic molecules (CSF-1 and MCP-1). PMID:18705801

THE RELATIONSHIP OF THE CHEMOTACTIC BEHAVIOR OF THE COMPLEMENT-DERIVED FACTORS, C3a, C5a, AND C567, AND A BACTERIAL CHEMOTACTIC FACTOR TO THEIR ABILITY TO ACTIVATE THE PROESTERASE 1 OF RABBIT POLYMORPHONUCLEAR LEUKOCYTES

PubMed Central

Becker, Elmer L.

1972-01-01

The inhibition profiles obtained when a series of p-nitrophenyl ethyl alkylphosphonates and of p-nitrophenyl ethyl chloroalkylphosphonates were used to interfere with the chemotactic activity of polymorphonuclear leukocytes stimulated by C3a, C5a, and bacterial factor were the same as found previously when C567 was the chemotactic agent. This indicates that as in the chemotactic activity induced by C567, an obligatory step in the chemotaxis caused by C3a, C5a, and bacterial factor is the activation of proesterase 1 of the rabbit polymorphonuclear leukocyte. C5a and C3a activate proesterase 1 of peripheral blood polymophonuclear leukocytes as measured by the increase of acetyl DL-phenylalanine β-naphthyl esterase activity. Attempts to detect in a like manner the proesterase 1 of the same leukocytes using bacterial factor under varying circumstances have consistently failed. It is concluded that bacterial factor, for unknown reasons, is unable to activate proesterase 1 to the same extent as the complement-derived chemotactic factors. The hypothesis of there being a quantitative difference in the ability of bacterial factor to activate proesterase 1 compared with the complement-derived factors explains the previous observations that bacterial factor can not deactivate to itself or to the complement-derived factors, although these latter factors can deactivate to themselves, to each other, and to the bacterial factor. The quantitative difference in the ability of bacterial factor to activate proesterase 1 compared to the complement-derived factors is also associated with and explains the finding that the maximal chemotactic activity attainable when bacterial factor is the chemotactic agent is distinctly less than that obtained using either C3a, C5a, or C567. These results indicate that the activation of proesterase 1 is a general requirement for the chemotactic activity of rabbit polymorphonuclear leukocytes with known macromolecular chemotactic agents and suggest that under several different circumstances the level of chemotactic activity attained is related to the degree of such activation. PMID:4551218

Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

PubMed

Park, H S; Jung, K S

1998-03-01

There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

NASA Astrophysics Data System (ADS)

Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

1984-01-01

Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

Chemotaxing and haptotaxing random walkers having directional persistence

NASA Astrophysics Data System (ADS)

Kwon, Tae Goo; Kyoungjin Lee Team; Taeseok Daniel Yang Team

2015-03-01

Biological cell crawling is a rather complex process involving various bio-chemical and bio-mechanical processes, many of which are still not well understood. The difficulties in understanding the crawling are originating not just from cell-intrinsic factors but from their complex social interactions, cell-to-substrate interactions and nonlinear responses toward extrinsic factors. Here, in this report we investigate chemotactic behavior of mathematical model cells that naturally have directional persistence. A cell density is measured as a function of time and space, then the resulting steady state is compared with that of the well-known Keller-Segal model, which describes a population of chemotactic random walker. Then, we add a cell-to-cell interaction, mimicking a ``haptotaxis'' mediated interaction, to the model and access its role as for altering the steady-state cell density profile. This mathematical model system, which we have developed and considered in this work, can be quite relevant to the chemotactic responses of interacting immune cells, like microglia, moving toward and around a site of wound, as for an example. We conclude by discussing some relevant recent experimental findings.

A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

PubMed

Shak, S; Perez, H D; Goldstein, I M

1983-12-25

We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco) and Its Active Site for Chemotaxis

PubMed Central

Dawar, Farman Ullah; Tu, Jiagang; Xiong, Yang; Lan, Jiangfeng; Dong, Xing Xing; Liu, Xiaoling; Khattak, Muhammad Nasir Khan; Mei, Jie; Lin, Li

2016-01-01

Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA), a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase) activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS). The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals) at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics. PMID:27589721

Computational and Theoretical Study of the Physical Constraints on Chemotaxis

NASA Astrophysics Data System (ADS)

Varennes, Julien

Cell chemotaxis is crucial to many biological functions including development, wound healing, and cancer metastasis. Chemotaxis is the process in which cells migrate in response to chemical concentration gradients. Recent experiments show that cells are capable of detecting shallow gradients as small as a 1% concentration difference, and multicellular groups can improve on this by an additional order of magnitude. Examples from morphogenesis and metastasis demonstrate collective response to gradients equivalent to a 1 molecule difference in concentration across a cell body. While the physical constraints to cell gradient sensing are well understood, how the sensory information leads to cell migration, and coherent multicellular movement in the case of collectives, remains poorly understood. Here we examine how extrinsic sensory noise leads to error in chemotactic performance. First, we study single cell chemotaxis and use both simulations and analytical models to place physical constraints on chemotactic performance. Next we turn our attention to collective chemotaxis. We examine how collective cell interactions can improve chemotactic performance. We develop a novel model for quantifying the physical limit to chemotactic precision for two stereotypical modes of collective chemotaxis. Finally, we conclude by examining the effects of intercellular communication on collective chemotaxis. We use simulations to test how well collectives can chemotax through very shallow gradients with the help of communication. By studying these computational and theoretical models of individual and collective chemotaxis, we address the gap in knowledge between chemical sensing and directed migration.

Amygdalin blocks the in vitro adhesion and invasion of renal cell carcinoma cells by an integrin-dependent mechanism.

PubMed

Juengel, Eva; Afschar, Masud; Makarević, Jasmina; Rutz, Jochen; Tsaur, Igor; Mani, Jens; Nelson, Karen; Haferkamp, Axel; Blaheta, Roman A

2016-03-01

Information about the natural compound amygdalin, which is employed as an antitumor agent, is sparse and thus its efficacy remains controversial. In this study, to determine whether amygdalin exerts antitumor effects on renal cell carcinoma (RCC) cells, its impact on RCC metastatic activity was investigated. The RCC cell lines, Caki-1, KTC-26 and A498, were exposed to amygdalin from apricot kernels, and adhesion to human vascular endothelium, immobilized collagen or fibronectin was investigated. The influence of amygdalin on chemotactic and invasive activity was also determined, as was the influence of amygdalin on surface and total cellular α and β integrin expression, which are involved in metastasis. We noted that amygdalin caused significant reductions in chemotactic activity, invasion and adhesion to endothelium, collagen and fibronectin. Using FACScan analysis, we noted that amygdalin also induced reductions, particularly in integrins α5 and α6, in all three cell lines. Functional blocking of α5 resulted in significantly diminished adhesion of KTC-26 and A498 to collagen and also in decreased chemotactic behavior in all three cell lines. Blocking α6 integrin significantly reduced chemotactic activity in all three cell lines. Thus, we suggest that exposing RCC cells to amygdalin inhibits metastatic spread and is associated with downregulation of α5 and α6 integrins. Therefore, we posit that amygdalin exerts antitumor activity in vitro, and this may be linked to integrin regulation.

Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors.

PubMed

Idzko, Marco; Dichmann, Stefan; Ferrari, Davide; Di Virgilio, Francesco; la Sala, Andrea; Girolomoni, Giampiero; Panther, Elisabeth; Norgauer, Johannes

2002-08-01

Dendritic cells (DCs) are considered the principal initiators of immune response because of their ability to migrate into peripheral tissues and lymphoid organs, process antigens, and activate naive T cells. There is evidence that extracellular nucleotides regulate certain functions of DCs via G-protein-coupled P2Y receptors (P2YR) and ion-channel-gated P2X receptors (P2XR). Here we investigated the chemotactic activity and analyzed the migration-associated intracellular signaling events such as actin reorganization and Ca(++) transients induced by common P2R agonists such as adenosine 5'-triphosphate (ATP) and 2-methylthioadenosine triphosphate, the P2YR agonists UTP and adenosine 5'-diphosphate (ADP), or the P2XR agonists alphabeta-methylenadenosine-5'-triphosphate and 2',3'-(4-benzoyl)benzoyl-ATP. The common P2R agonists and the selective P2YR agonists turned out to be potent chemotactic stimuli for immature DCs, but not for mature DCs. In contrast, P2XR agonists had only marginal chemotactic activity in both DC types. Chemotaxis was paralleled by a rise in the intracellular Ca(++) concentration and by actin polymerization. Studies with pertussis toxin implicated that intracellular signaling events such as actin polymerization, mobilization of intracellular Ca(++), and migration induced by nucleotides was mediated via G(i/o) protein-coupled P2YR. Moreover, functional studies revealed selective down-regulation of this G(i/o) protein-coupled chemotactic P2YR responsiveness during maturation, although immature and mature DCs expressed similar amounts of mRNA for the P2R subtypes (P2Y(2)R, P2Y(4)R, P2Y(5)R, P2Y(7)R, P2Y(11)R and P2X(1)R, P2X(4)R, P2X(7)R), and no major differences in respect to the mRNA expression of these receptors could be observed by semiquantitative reverse transcription and polymerase chain reaction (RT-PCR). In summary, our data describe a differential chemotactic response of immature and mature DCs to nucleotides, and lend further support to the hypothesis that P2R are a novel class of immunomodulatory plasma membrane receptors suitable for pharmacological intervention.

The group VIA calcium-independent phospholipase A2 and NFATc4 pathway mediates IL-1β-induced expression of chemokines CCL2 and CXCL10 in rat fibroblasts.

PubMed

Kuwata, Hiroshi; Yuzurihara, Chihiro; Kinoshita, Natsumi; Taki, Yuki; Ikegami, Yuki; Washio, Sana; Hirakawa, Yushi; Yoda, Emiko; Aiuchi, Toshihiro; Itabe, Hiroyuki; Nakatani, Yoshihito; Hara, Shuntaro

2018-06-01

Chemokines are secreted proteins that regulate cell migration and are involved in inflammatory and immune responses. Here, we sought to define the functional crosstalk between the lipid signaling and chemokine signaling. We obtained evidence that the induction of some chemokines is regulated by group VIA calcium-independent phospholipase A 2 β (iPLA 2 β) in IL-1β-stimulated rat fibroblastic 3Y1 cells. Treatment of 3Y1 cells with IL-1β elicited an increased release of chemotactic factor(s) for monocytic THP-1 cells into culture medium in a time-dependent manner. Inhibitor studies revealed that an intracellular PLA 2 inhibitor, arachidonoyl trifluoromethyl ketone (AACOCF 3 ), but not the cyclooxygenase inhibitor indomethacin, attenuated the release of chemotactic factor(s). The chemotactic activity was inactivated by treatment with either heat or proteinase K, suggesting this chemotactic factor(s) is a proteinaceous factor(s). We purified the chemotactic factor(s) from the conditioned medium of IL-1β-stimulated 3Y1 cells using a heparin column and identified several chemokines, including CCL2 and CXCL10. The inducible expressions of CCL2 and CXCL10 were significantly attenuated by pretreatment with AACOCF 3 . Gene silencing using siRNA revealed that the inductions of CCL2 and CXCL10 were attenuated by iPLA 2 β knockdown. Additionally, the transcriptional activation of nuclear factor of activated T-cell proteins (NFATs), but not nuclear factor-κB, by IL-1β stimulation was markedly attenuated by the iPLA 2 inhibitor bromoenol lactone, and NFATc4 knockdown markedly attenuated the IL-1β-induced expression of both CCL2 and CXCL10. Collectively, these results indicated that iPLA 2 β plays roles in IL-1β-induced chemokine expression, in part via NFATc4 signaling. © 2018 Federation of European Biochemical Societies.

Chemotactic activity from rabbit peritoneal neutrophils. Lack of identity with N-acetyl-DL-phenylalanine beta-napthyl esterase.

PubMed

Tsung, P K; Showell, H J; Kegeles, S W; Becker, E L

1976-08-12

The chemotactic and N-acetyl-DL-phenylalanine beta-naphthyl esterase activities of rabbit peritoneal neutrophils are separable from each other by both DEAE cellulose and Sephadex G-100 column chromatography. Partially purified esterase obtained from DEAE-cellulose chromatography had molecular weight of 70 000. However, the partially purified fraction contained chemotactic activities with major activity in molecular weight of 28000 and minor activities in the molecular weights of 45000, 21900, 14500 and 10500. Esterase activity is inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate but chemotactic activity is not.

Revisiting chemoaffinity theory: Chemotactic implementation of topographic axonal projection

PubMed Central

2017-01-01

Neural circuits are wired by chemotactic migration of growth cones guided by extracellular guidance cue gradients. How growth cone chemotaxis builds the macroscopic structure of the neural circuit is a fundamental question in neuroscience. I addressed this issue in the case of the ordered axonal projections called topographic maps in the retinotectal system. In the retina and tectum, the erythropoietin-producing hepatocellular (Eph) receptors and their ligands, the ephrins, are expressed in gradients. According to Sperry’s chemoaffinity theory, gradients in both the source and target areas enable projecting axons to recognize their proper terminals, but how axons chemotactically decode their destinations is largely unknown. To identify the chemotactic mechanism of topographic mapping, I developed a mathematical model of intracellular signaling in the growth cone that focuses on the growth cone’s unique chemotactic property of being attracted or repelled by the same guidance cues in different biological situations. The model presented mechanism by which the retinal growth cone reaches the correct terminal zone in the tectum through alternating chemotactic response between attraction and repulsion around a preferred concentration. The model also provided a unified understanding of the contrasting relationships between receptor expression levels and preferred ligand concentrations in EphA/ephrinA- and EphB/ephrinB-encoded topographic mappings. Thus, this study redefines the chemoaffinity theory in chemotactic terms. PMID:28792499

Spatial control of actin polymerization during neutrophil chemotaxis

PubMed Central

Weiner, Orion D.; Servant, Guy; Welch, Matthew D.; Mitchison, Timothy J.; Sedat, John W.; Bourne, Henry R.

2010-01-01

Neutrophils respond to chemotactic stimuli by increasing the nucleation and polymerization of actin filaments, but the location and regulation of these processes are not well understood. Here, using a permeabilized-cell assay, we show that chemotactic stimuli cause neutrophils to organize many discrete sites of actin polymerization, the distribution of which is biased by external chemotactic gradients. Furthermore, the Arp2/3 complex, which can nucleate actin polymerization, dynamically redistributes to the region of living neutrophils that receives maximal chemotactic stimulation, and the least-extractable pool of the Arp2/3 complex co-localizes with sites of actin polymerization. Our observations indicate that chemoattractant-stimulated neutrophils may establish discrete foci of actin polymerization that are similar to those generated at the posterior surface of the intracellular bacterium Listeria monocytogenes. We propose that asymmetrical establishment and/or maintenance of sites of actin polymerization produces directional migration of neutrophils in response to chemotactic gradients. PMID:10559877

Spatial control of actin polymerization during neutrophil chemotaxis.

PubMed

Weiner, O D; Servant, G; Welch, M D; Mitchison, T J; Sedat, J W; Bourne, H R

1999-06-01

Neutrophils respond to chemotactic stimuli by increasing the nucleation and polymerization of actin filaments, but the location and regulation of these processes are not well understood. Here, using a permeabilized-cell assay, we show that chemotactic stimuli cause neutrophils to organize many discrete sites of actin polymerization, the distribution of which is biased by external chemotactic gradients. Furthermore, the Arp2/3 complex, which can nucleate actin polymerization, dynamically redistributes to the region of living neutrophils that receives maximal chemotactic stimulation, and the least-extractable pool of the Arp2/3 complex co-localizes with sites of actin polymerization. Our observations indicate that chemoattractant-stimulated neutrophils may establish discrete foci of actin polymerization that are similar to those generated at the posterior surface of the intracellular bacterium Listeria monocytogenes. We propose that asymmetrical establishment and/or maintenance of sites of actin polymerization produces directional migration of neutrophils in response to chemotactic gradients.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasui, K.; Yamazaki, M.; Miyagawa, Y.

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 (/sup 3/H-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 ofmore » neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder.« less

A Plasma Protein Indistinguishable from Ribosomal Protein S19

PubMed Central

Semba, Umeko; Chen, Jun; Ota, Yoshihiko; Jia, Nan; Arima, Hidetoshi; Nishiura, Hiroshi; Yamamoto, Tetsuro

2010-01-01

A monocyte-chemoattracting factor is generated during blood coagulation and during clotting of platelet-rich plasma. This chemotactic factor attracts monocytes as a ligand of the C5a receptor; however, it inhibits C5a-induced neutrophil chemotaxis as an apparent receptor antagonist. The curious dual function of the serum monocyte chemotactic factor resembles that of the cross-linked homodimer of ribosomal protein S19 (RP S19). Indeed, the inactive precursor of the monocyte chemotactic factor was present in plasma, and the precursor molecule and RP S19, as well as the active form and the RP S19 dimer, were indistinguishable in terms of immunological reactivity and molecular size. Coagulation factor XIIIa, plasma transglutaminase, and membrane phosphatidylserine on the activated platelets were required for conversion of the precursor to the active form. In addition, the precursor molecule in plasma could be replaced by wild-type recombinant RP S19 but not by mutant forms of it. These results indicate that a molecule indistinguishable from RP S19 was present in plasma, and that the RP S19-like molecule was converted to the active form by a transglutaminase-catalyzed reaction on a scaffold that included the phosphatidylserine-exposed platelet membrane. PMID:20093496

Adaptive microfluidic gradient generator for quantitative chemotaxis experiments.

PubMed

Anielski, Alexander; Pfannes, Eva K B; Beta, Carsten

2017-03-01

Chemotactic motion in a chemical gradient is an essential cellular function that controls many processes in the living world. For a better understanding and more detailed modelling of the underlying mechanisms of chemotaxis, quantitative investigations in controlled environments are needed. We developed a setup that allows us to separately address the dependencies of the chemotactic motion on the average background concentration and on the gradient steepness of the chemoattractant. In particular, both the background concentration and the gradient steepness can be kept constant at the position of the cell while it moves along in the gradient direction. This is achieved by generating a well-defined chemoattractant gradient using flow photolysis. In this approach, the chemoattractant is released by a light-induced reaction from a caged precursor in a microfluidic flow chamber upstream of the cell. The flow photolysis approach is combined with an automated real-time cell tracker that determines changes in the cell position and triggers movement of the microscope stage such that the cell motion is compensated and the cell remains at the same position in the gradient profile. The gradient profile can be either determined experimentally using a caged fluorescent dye or may be alternatively determined by numerical solutions of the corresponding physical model. To demonstrate the function of this adaptive microfluidic gradient generator, we compare the chemotactic motion of Dictyostelium discoideum cells in a static gradient and in a gradient that adapts to the position of the moving cell.

Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

PubMed Central

Llewellyn-Jones, C. G.; Hill, S. L.; Stockley, R. A.

1994-01-01

BACKGROUND--Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. METHODS--The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. RESULTS--Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. CONCLUSIONS--These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue. PMID:8202875

Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

PubMed

Llewellyn-Jones, C G; Hill, S L; Stockley, R A

1994-03-01

Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

Microcystins Alter Chemotactic Behavior in Caenorhabditis elegans by Selectively Targeting the AWA Sensory Neuron

PubMed Central

Moore, Caroline E.; Lein, Pamela J.; Puschner, Birgit

2014-01-01

Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition. PMID:24918360

An intact acrosome is required for the chemotactic response to progesterone in mouse spermatozoa.

PubMed

Guidobaldi, Hector A; Hirohashi, Noritaka; Cubilla, Marisa; Buffone, Mariano G; Giojalas, Laura C

2017-04-01

Mammalian sperm become fertilization-competent in the oviduct, during a process known as capacitation that involves the acquisition of the ability to exocytose the acrosome but also the chemotactic responses-both of which contribute to successful fertilization. Chemotaxis is used by spermatozoa to orient and to locate the egg; the acrosome reaction facilitates sperm binding to and fusing with the egg membrane. Mammalian spermatozoa are able to sense picomolar concentrations of progesterone, which drives chemotactic behavior. The state of the acrosome during the chemotactic response, however, is unknown. Genetically modified mouse spermatozoa were employed in a chemotaxis assay under fluorescence microscopy to evaluate their acrosome status while swimming, allowing us to elucidate the acrosome integrity of sperm responding to progesterone-induced chemotaxis. We first showed that wild-type mouse spermatozoa chemotactically respond to a gradient of progesterone, and that the genetic modifications employed do not affect the chemotactic behavior of sperm to progesterone. Next, we found that acrosome-intact, but not acrosome-reacted, spermatozoa orient and respond to picomolar concentrations of progesterone and that chemotaxis normally occurs prior to the acrosome reaction. Our results suggest that premature commitment to acrosome exocytosis leads to navigation failure, so proper control and timing of the acrosome reaction is required for fertilization success and male fertility. © 2017 Wiley Periodicals, Inc.

Chemotactic activity of cotyledons for mononuclear leukocytes related to occurrence of retained placenta in dexamethasone induced parturition in cattle.

PubMed

Benedictus, L; Jorritsma, R; Knijn, H M; Vos, P L A M; Koets, A P

2011-09-15

Induction of parturition with glucocorticosteroids in cattle is used for research purposes, in diseased or injured pregnant cows, and as a management tool to time parturition. A negative side effect of induction of parturition with glucocorticosteroids is the high incidence of retained placenta that occurs after these calvings. Reaction of the maternal immune system against the 'foreign' foetal membranes contributes to the breakdown of the foetal-maternal attachment. Several studies indicate that failure of this immune assisted detachment increases the occurrence of retained placenta. We hypothesized that retained placenta occurring after induction of parturition with glucocorticosteroids is caused by failure of immune assisted detachment of the foetal membranes. The chemotactic activity of cotyledons for mononuclear leukocytes was used as a parameter to see whether immune assisted detachment of the foetal membranes had occurred. Cotyledons were collected from spontaneously calving non-retained placenta cows and from dexamethasone induced non-retained placenta and retained placenta cows. The study showed that the chemotactic activity of cotyledons for mononuclear leukocytes was lower (P < 0.001) in cotyledons obtained from retained placenta cows in which parturition was induced with dexamethasone compared to the chemotactic activity of cotyledons obtained from spontaneously calving non-retained placenta cows, whereas the chemotactic activity of cotyledons obtained from induced non-retained placenta cows was not lower (P = 0.10) than the chemotactic activity of cotyledons obtained from spontaneously calving non-retained placenta cows. We concluded that induction of parturition with dexamethasone causes a failure of immune assisted detachment of the foetal membranes and the accompanying release of chemotactic factors. As a result, the chemotactic activity of cotyledons for mononuclear leukocytes is lower in induced retained placenta cows than in cotyledons from non-retained placenta cows in which successful immune assisted detachment of the foetal membranes occurs. Copyright © 2011 Elsevier Inc. All rights reserved.

Eukaryotic Chemotaxis: A Network of Signaling Pathways Controls Motility, Directional Sensing, and Polarity

PubMed Central

Swaney, Kristen F.; Huang, Chuan-Hsiang; Devreotes, Peter N.

2015-01-01

Chemotaxis, the directed migration of cells in chemical gradients, is a vital process in normal physiology and in the pathogenesis of many diseases. Chemotactic cells display motility, directional sensing, and polarity. Motility refers to the random extension of pseudopodia, which may be driven by spontaneous actin waves that propagate through the cytoskeleton. Directional sensing is mediated by a system that detects temporal and spatial stimuli and biases motility toward the gradient. Polarity gives cells morphologically and functionally distinct leading and lagging edges by relocating proteins or their activities selectively to the poles. By exploiting the genetic advantages of Dictyostelium, investigators are working out the complex network of interactions between the proteins that have been implicated in the chemotactic processes of motility, directional sensing, and polarity. PMID:20192768

Multiscale dynamics of biological cells with chemotactic interactions: From a discrete stochastic model to a continuous description

NASA Astrophysics Data System (ADS)

Alber, Mark; Chen, Nan; Glimm, Tilmann; Lushnikov, Pavel M.

2006-05-01

The cellular Potts model (CPM) has been used for simulating various biological phenomena such as differential adhesion, fruiting body formation of the slime mold Dictyostelium discoideum, angiogenesis, cancer invasion, chondrogenesis in embryonic vertebrate limbs, and many others. We derive a continuous limit of a discrete one-dimensional CPM with the chemotactic interactions between cells in the form of a Fokker-Planck equation for the evolution of the cell probability density function. This equation is then reduced to the classical macroscopic Keller-Segel model. In particular, all coefficients of the Keller-Segel model are obtained from parameters of the CPM. Theoretical results are verified numerically by comparing Monte Carlo simulations for the CPM with numerics for the Keller-Segel model.

CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells.

PubMed

Guo, Na; Zhang, Kui; Lv, Minghua; Miao, Jinlin; Chen, Zhinan; Zhu, Ping

2015-02-01

Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

PubMed

Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

2008-06-01

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

Perspectives in flow-based microfluidic gradient generators for characterizing bacterial chemotaxis

PubMed Central

Wolfram, Christopher J.; Rubloff, Gary W.; Luo, Xiaolong

2016-01-01

Chemotaxis is a phenomenon which enables cells to sense concentrations of certain chemical species in their microenvironment and move towards chemically favorable regions. Recent advances in microbiology have engineered the chemotactic properties of bacteria to perform novel functions, but traditional methods of characterizing chemotaxis do not fully capture the associated cell motion, making it difficult to infer mechanisms that link the motion to the microbiology which induces it. Microfluidics offers a potential solution in the form of gradient generators. Many of the gradient generators studied to date for this application are flow-based, where a chemical species diffuses across the laminar flow interface between two solutions moving through a microchannel. Despite significant research efforts, flow-based gradient generators have achieved mixed success at accurately capturing the highly subtle chemotactic responses exhibited by bacteria. Here we present an analysis encompassing previously published versions of flow-based gradient generators, the theories that govern their gradient-generating properties, and new, more practical considerations that result from experimental factors. We conclude that flow-based gradient generators present a challenge inherent to their design in that the residence time and gradient decay must be finely balanced, and that this significantly narrows the window for reliable observation and quantification of chemotactic motion. This challenge is compounded by the effects of shear on an ellipsoidal bacterium that causes it to preferentially align with the direction of flow and subsequently suppresses the cross-flow chemotactic response. These problems suggest that a static, non-flowing gradient generator may be a more suitable platform for chemotaxis studies in the long run, despite posing greater difficulties in design and fabrication. PMID:27917249

Perspectives in flow-based microfluidic gradient generators for characterizing bacterial chemotaxis.

PubMed

Wolfram, Christopher J; Rubloff, Gary W; Luo, Xiaolong

2016-11-01

Chemotaxis is a phenomenon which enables cells to sense concentrations of certain chemical species in their microenvironment and move towards chemically favorable regions. Recent advances in microbiology have engineered the chemotactic properties of bacteria to perform novel functions, but traditional methods of characterizing chemotaxis do not fully capture the associated cell motion, making it difficult to infer mechanisms that link the motion to the microbiology which induces it. Microfluidics offers a potential solution in the form of gradient generators. Many of the gradient generators studied to date for this application are flow-based, where a chemical species diffuses across the laminar flow interface between two solutions moving through a microchannel. Despite significant research efforts, flow-based gradient generators have achieved mixed success at accurately capturing the highly subtle chemotactic responses exhibited by bacteria. Here we present an analysis encompassing previously published versions of flow-based gradient generators, the theories that govern their gradient-generating properties, and new, more practical considerations that result from experimental factors. We conclude that flow-based gradient generators present a challenge inherent to their design in that the residence time and gradient decay must be finely balanced, and that this significantly narrows the window for reliable observation and quantification of chemotactic motion. This challenge is compounded by the effects of shear on an ellipsoidal bacterium that causes it to preferentially align with the direction of flow and subsequently suppresses the cross-flow chemotactic response. These problems suggest that a static, non-flowing gradient generator may be a more suitable platform for chemotaxis studies in the long run, despite posing greater difficulties in design and fabrication.

The effects of oral consumption of selenium nanoparticles on chemotactic and respiratory burst activities of neutrophils in comparison with sodium selenite in sheep.

PubMed

Kojouri, Gholam Ali; Sadeghian, Sirous; Mohebbi, Abdonnaser; Mokhber Dezfouli, Mohammad Reza

2012-05-01

The present study was designed to compare the effects of nano-selenium and of sodium selenite on the chemotactic and respiratory burst activities of neutrophils in sheep. Fifteen sheep were randomly divided into three groups. Groups 1 and 2 received selenium nanoparticles (1 mg/kg) or sodium selenite (1 mg/kg) orally, respectively, for ten consecutive days, and the third group was considered as the control. To determine the chemotactic and respiratory burst activities of the neutrophils, the leading front assay and the NBT test were used on heparinized blood samples that were collected at different intervals (days 0, 10th, 20th, and 30th). The results obtained showed that the chemotactic activities in groups 1 and 2 increased significantly on the 10th, 20th, and 30th day, compared to day 0, and on the 20th day in comparison with the 10th day, while in group 2, there was a significant decrease on the 30th day compared to the 20th day. The chemotactic activities in group 1 were significantly higher than in group 2 on the 10th day and in the control group on the 10th, 20th, and 30th day, but the chemotactic activities in group 2 were significantly higher than those in the control group only on the 20th day. On the 30th day into the experiment, the respiratory bursts in groups 1 and 2 were significantly stronger in comparison with those at day 0. Overall, nano-selenium increased the chemotactic and respiratory burst activities more significantly than sodium selenite, which is suggestive of a stronger stimulatory effect of the Se nanoparticles on intracellular activities.

Urease-independent chemotactic responses of Helicobacter pylori to urea, urease inhibitors, and sodium bicarbonate.

PubMed Central

Mizote, T; Yoshiyama, H; Nakazawa, T

1997-01-01

Helicobacter pylori CPY3401 and an isogenic urease-negative mutant, HPT73, showed chemotactic responses to urea, flurofamide (a potent urease inhibitor), and sodium bicarbonate. Since urea and sodium bicarbonate are secreted through the gastric epithelial surface and hydrolysis of urea by urease on the bacterial surface is essential for colonization, the chemotactic response of H. pylori may be crucial for its colonization and persistence in the stomach. PMID:9119496

EXPERIMENTAL STUDIES ON INFLAMMATION

PubMed Central

Wolf, Elizabeth Pauline

1921-01-01

1. Wright's method for the study of chemotaxis of leucocytes in vitro, slightly modified, has been found to be most satisfactory in the estimation of the degree of chemotaxis of various substances, because it is possible to make an exact quantitative determination of the leucocytes that have migrated from the blood clot and adhere to the surfaces containing the tested substance. 2. The calcium ion is the only inorganic ion per se which is found to be positively chemotactic under the conditions of these experiments. It is markedly chemotactic in all concentrations and in all combinations, except the citrate. Here the negative chemotaxis of the citrate ion neutralizes the positive chemotaxis of the calcium ion, and neutrality of chemotactic effect results. 3. The sodium and magnesium ions themselves are neutral. Magnesium and sodium salts are dependent upon the negative ion with which the magnesium or sodium is combined for such positive or negative chemotaxis as is exhibited. All the phosphates of sodium, whether tri-, di-, or monobasic salts, are markedly positively chemotactic, and when combined with other reagents which are themselves neutral or negatively chemotactic, produce marked positive chemotaxis. The blood of a person who has taken phosphates either by mouth or intravenously shows a great increase in chemotaxis with sodium phosphate, with calcium chloride, and even with sodium chloride which is ordinarily neutral. 4. All potassium salts are negatively chemotactic. 5. Many substances act synergistically as regards chemotaxis; e.g., when strontium and magnesium salts are mixed there is a marked increase in chemotaxis. Sodium phosphate acts synergistically with calcium chloride. 6. Mercury salts fix the leucocytes in this method so that their influence on chemotaxis cannot be determined. 7. Morphine and morphine salts are positively chemotactic; this is contrary to the results obtained by others with different methods. 8. Substances which produce a very acute inflammation, such as cantharidin, histamine, or turpentine, are found to be positively chemotactic by this method, but substances, such as mustard gas, which produce a marked necrotizing effect are found to be negatively chemotactic, or neutral, though physiologically they would appear to be positively chemotactic. 9. All amino-acids and amines are positively chemotactic to a certain extent. It seems that the longer the carbon chain, the greater the degree of chemotaxis, though this is not absolute. Tyramine is one exception to this, for it causes a peculiar clumping of the cells, so that it is impossible to count the number adhering, and thus determine whether or not tyramine is positively chemotactic. 10. The time that the blood of animals is examined after eating makes a marked difference in the number of cells adhering, for shortly after eating, within 30 minutes, very many more cells will adhere to the agar than at a later time. 11. The blood of different species of animals reacts differently towards different reagents. The chemical composition of these agents seems to have nothing to do with this difference in reaction as far as we could determine. 12. With frozen serial sections it has been found that the depth of penetration of the leucocytes into the agar is proportional to the positive chemotaxis produced by the substance combined with the agar, as demonstrated by the number of leucocytes adherent to the walls of the test chambers. PMID:19868564

EXPERIMENTAL STUDIES ON INFLAMMATION : I. THE INFLUENCE OF CHEMICALS UPON THE CHEMOTAXIS OF LEUCOCYTES IN VITRO.

PubMed

Wolf, E P

1921-09-30

1. Wright's method for the study of chemotaxis of leucocytes in vitro, slightly modified, has been found to be most satisfactory in the estimation of the degree of chemotaxis of various substances, because it is possible to make an exact quantitative determination of the leucocytes that have migrated from the blood clot and adhere to the surfaces containing the tested substance. 2. The calcium ion is the only inorganic ion per se which is found to be positively chemotactic under the conditions of these experiments. It is markedly chemotactic in all concentrations and in all combinations, except the citrate. Here the negative chemotaxis of the citrate ion neutralizes the positive chemotaxis of the calcium ion, and neutrality of chemotactic effect results. 3. The sodium and magnesium ions themselves are neutral. Magnesium and sodium salts are dependent upon the negative ion with which the magnesium or sodium is combined for such positive or negative chemotaxis as is exhibited. All the phosphates of sodium, whether tri-, di-, or monobasic salts, are markedly positively chemotactic, and when combined with other reagents which are themselves neutral or negatively chemotactic, produce marked positive chemotaxis. The blood of a person who has taken phosphates either by mouth or intravenously shows a great increase in chemotaxis with sodium phosphate, with calcium chloride, and even with sodium chloride which is ordinarily neutral. 4. All potassium salts are negatively chemotactic. 5. Many substances act synergistically as regards chemotaxis; e.g., when strontium and magnesium salts are mixed there is a marked increase in chemotaxis. Sodium phosphate acts synergistically with calcium chloride. 6. Mercury salts fix the leucocytes in this method so that their influence on chemotaxis cannot be determined. 7. Morphine and morphine salts are positively chemotactic; this is contrary to the results obtained by others with different methods. 8. Substances which produce a very acute inflammation, such as cantharidin, histamine, or turpentine, are found to be positively chemotactic by this method, but substances, such as mustard gas, which produce a marked necrotizing effect are found to be negatively chemotactic, or neutral, though physiologically they would appear to be positively chemotactic. 9. All amino-acids and amines are positively chemotactic to a certain extent. It seems that the longer the carbon chain, the greater the degree of chemotaxis, though this is not absolute. Tyramine is one exception to this, for it causes a peculiar clumping of the cells, so that it is impossible to count the number adhering, and thus determine whether or not tyramine is positively chemotactic. 10. The time that the blood of animals is examined after eating makes a marked difference in the number of cells adhering, for shortly after eating, within 30 minutes, very many more cells will adhere to the agar than at a later time. 11. The blood of different species of animals reacts differently towards different reagents. The chemical composition of these agents seems to have nothing to do with this difference in reaction as far as we could determine. 12. With frozen serial sections it has been found that the depth of penetration of the leucocytes into the agar is proportional to the positive chemotaxis produced by the substance combined with the agar, as demonstrated by the number of leucocytes adherent to the walls of the test chambers.

Exploring Inflammatory Disease Drug Effects on Neutrophil Function

PubMed Central

Wu, Xiaojie; Kim, Donghyuk; Young, Ashlyn T.; Haynes, Christy L.

2014-01-01

Neutrophils are critical inflammatory cells; thus, it is important to characterize the effects of drugs on neutrophil function in the context of inflammatory diseases. Herein, chemically guided neutrophil migration, known as chemotaxis, is studied in the context of drug treatment at the single cell level using a microfluidic platform, complemented by cell viability assays and calcium imaging. Three representative drugs known to inhibit surface receptor expression, signaling enzyme activity, and the elevation of intracellular Ca2+ levels, each playing a significant role in neutrophil chemotactic pathways, are used to examine the in vitro drug effects on cellular behaviors. The microfluidic device establishes a stable concentration gradient of chemokines across a cell culture chamber so that neutrophil migration can be monitored under various drug-exposure conditions. Different time- and concentration-dependent regulatory effects were observed by comparing the motility, polarization, and effectiveness of neutrophil chemotaxis in response to the three drugs. Viability assays revealed distinct drug capabilities in reducing neutrophil viability while calcium imaging clarified the role of Ca2+ in the neutrophil chemotactic pathway. This study provides mechanistic insight into the drug effects on neutrophil function, facilitating comparison of current and potential pharmaceutical approaches. PMID:24946254

The chemotactic activity of sputum from patients with bronchiectasis.

PubMed

Mikami, M; Llewellyn-Jones, C G; Bayley, D; Hill, S L; Stockley, R A

1998-03-01

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Generation and partial characterization of an eosinophil chemotactic cytokine produced by sensitized equine mononuclear cells stimulated with Strongylus vulgaris antigen.

PubMed

Dennis, V A; Klei, T R; Chapman, M R

1993-07-01

Supernatants generated by stimulation of peripheral blood mononuclear cells (PBMC) from Strongylus vulgaris sensitized or immunized ponies were assayed in vitro for eosinophil chemotactic activity (ECA) using the filter system in blind well chambers. The supernatants from these cultures were chemotactic for eosinophils, but not for neutrophils. Supernates from cultures of unsensitized PBMC stimulated with S. vulgaris antigen were not chemotactic for eosinophils. ECA was first detected in culture supernatants after 1.5 h of incubation and was dependent on both antigen and PBMC concentrations, but independent of serum concentrations. Both female and male S. vulgaris worm antigens stimulated ECA production from sensitized PBMC. ECA was not induced by in vitro stimulation of sensitized S. vulgaris PBMC by female Strongylus edentatus worm antigen. Partial characterization of the eosinophil chemotactic cytokine showed it to be nondialyzable, greater than 8000 molecular weight (MW), and sensitive to heating (56 and 95 degrees C), trypsin, and sodium metaperiodate treatments, suggesting that the cytokine is a protein containing some essential carbohydrate moieties. The cytokine described in this paper could partially contribute to the in vivo blood and tissue eosinophilia in experimental S. vulgaris infection.

Structural and Functional Analysis of HIV-1 Coreceptors: Roles of Charged Residues and Posttranslational Modifications on Coreceptor Activity

DTIC Science & Technology

2000-01-01

to sites of inflammation. They may have additional functions. For example analysis of CXCR4 knockout mice show that CXCR4, which is chemotactic for... mice had similar phenotypes (195). Homozygous knockout of CXCR4 or SDF-1 results in embyonic lethality. Though CCR5 appears to be dispensable, other...chemokine receptors have vital functions. CXCR5 knockout mice have B-cell homing defects (118), and CXCR2 knockout mice overproduce B-cells and

Effect of fluticasone propionate on sputum of patients with chronic bronchitis and emphysema.

PubMed

Llewellyn-Jones, C G; Harris, T A; Stockley, R A

1996-02-01

The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age) were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group (p < 0.01). Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/- 1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05) pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054) after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period. Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations. The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung, and also by directly affecting the proteinase/antiproteinase balance, in favor of antiproteinases, within lung secretions.

Antimicrobial peptide scolopendrasin VII, derived from the centipede Scolopendra subspinipes mutilans, stimulates macrophage chemotaxis via formyl peptide receptor 1

PubMed Central

Park, Yoo Jung; Lee, Ha Young; Jung, Young Su; Park, Joon Seong; Hwang, Jae Sam; Bae, Yoe-Sik

2015-01-01

In this study, we report that one of the antimicrobial peptides scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates actin polymerization and the subsequent chemotactic migration of macrophages through the activation of ERK and protein kinase B (Akt) activity. The scolopendrasin VII-induced chemotactic migration of macrophages is inhibited by the formyl peptide receptor 1 (FPR1) antagonist cyclosporine H. We also found that scolopendrasin VII stimulate the chemotactic migration of FPR1-transfected RBL-2H3 cells, but not that of vector-transfected cells; moreover, scolopendrasin VII directly binds to FPR1. Our findings therefore suggest that the antimicrobial peptide scolopendrasin VII, derived from Scolopendra subspinipes mutilans, stimulates macrophages, resulting in chemotactic migration via FPR1 signaling, and the peptide can be useful in the study of FPR1-related biological responses. [BMB Reports 2015; 48(8): 479-484] PMID:26129676

Relation between chemotaxis and consumption of amino acids in bacteria

PubMed Central

Yang, Yiling; M. Pollard, Abiola; Höfler, Carolin; Poschet, Gernot; Wirtz, Markus; Hell, Rüdiger

2015-01-01

Summary Chemotaxis enables bacteria to navigate chemical gradients in their environment, accumulating toward high concentrations of attractants and avoiding high concentrations of repellents. Although finding nutrients is likely to be an important function of bacterial chemotaxis, not all characterized attractants are nutrients. Moreover, even for potential nutrients, the exact relation between the metabolic value of chemicals and their efficiency as chemoattractants has not been systematically explored. Here we compare the chemotactic response of amino acids with their use by bacteria for two well‐established models of chemotactic behavior, E scherichia coli and B acillus subtilis. We demonstrate that in E . coli chemotaxis toward amino acids indeed strongly correlates with their utilization. However, no such correlation is observed for B . subtilis, suggesting that in this case, the amino acids are not followed because of their nutritional value but rather as environmental cues. PMID:25807888

Enhanced Retention of Chemotactic Bacteria in a Pore Network with Residual NAPL Contamination

NASA Astrophysics Data System (ADS)

Ford, R.; Wang, X.

2013-12-01

Nonaqueous phase liquid (NAPL) contaminants are difficult to eliminate from natural aquifers due, in part, to the heterogeneous structure of the soil matrix. Residual NAPL ganglia remain trapped in regions where the hydraulic conductivity is relatively low. Bioremediation processes depend on adequate mixing of microbial populations and the groundwater contaminants that they degrade. The ability of bacteria to sense a chemical gradient and swim preferentially toward locations of higher concentration, known as chemotaxis, can enhance the mixing of bacteria with contaminant sources that may not be readily accessible by advection and dispersion alone. The impact of chemotaxis on bacterial abundance within a low conductivity NAPL-contaminated region of a well-characterized porous matrix was investigated. A microfluidic device was designed to mimic heterogeneous features of a contaminated groundwater system. NAPL ganglia (toluene) were trapped within a fine pore network, and bacteria were injected into the system through a highly conductive adjacent channel. Chemotactic bacteria (P. putida F1) migrated preferentially towards and accumulated in the vicinity of NAPL contaminant sources. The accumulation of chemotactic bacteria was 15% greater in comparison to a nonchemotactic mutant (P. putida F1 CheA). Bacteria in the microfluidic device were subjected to different flow velocities from 0.25 to 5 m/d encompassing the range of typical groundwater flow rates. Chemotactic bacteria exhibited greater accumulation near the intersection between the macrochannel and the porous network at a flow velocity of 0.5 m/d than both the nonchemotactic mutant control and the chemotactic bacteria at a higher flow velocity of 5 m/d. Breakthrough curves observed at the outlet provided indirect evidence that chemotactic bacteria were retained within the contaminated low permeable region for a longer time than the nonchemotactic bacteria at a flow velocity of 0.25 m/d. This retention was diminished at a higher flow velocity of 5 m/d. Numerical solutions of the governing equations for bacterial transport yielded outcomes that were consistent with the experimental results, and statistical analysis also supported the experimental comparisons. The chemotactic response aided efficient delivery of bacteria to NAPL contaminant sources within the low conductivity pore network. Because toluene is degraded by P. putida F1, the greater accumulation of chemotactic bacteria around the NAPL sources is also expected to increase contaminant consumption and improve the efficiency of bioremediation.

Transport of Chemotactic Bacteria in Porous Media with Structured Heterogeneity

NASA Astrophysics Data System (ADS)

Ford, R. M.; Wang, M.; Liu, J.; Long, T.

2008-12-01

Chemical contaminants that become trapped in low permeability zones (e.g. clay lenses) are difficult to remediate using conventional pump-and-treat approaches. Chemotactic bacteria that are transported by groundwater through more permeable regions may migrate toward these less permeable zones in response to chemical gradients created by contaminant diffusion from the low permeability source, thereby enhancing the remediation process by directing bacteria to the contaminants they degrade. What effect does the heterogeneity associated with coarse- and fine-grained layers that are characteristic of natural groundwater environments have on the transport of microorganisms and their chemotactic response? To address this question experiments were conducted over a range of scales from a single capillary tube to a laboratory- scale column in both static and flowing systems with and without chemoattractant gradients. In static capillary assays, motile bacteria accumulated at the interface between an aqueous solution and a suspension of agarose particulates. In microfluidic devices with an array of staggered cylinders, chemotactic bacteria migrated transverse to flow in response to a chemoattractant gradient. In sand columns packed with a coarse-grained core and surrounded by a fine-grained annulus, chemotactic bacteria migrated preferentially toward a chemoattractant source along the centerline. Mathematical models and computer simulations were developed to analyze the experimental observations in terms of transport parameters from the advection- disperson-sorption equation.

Migration of Chemotactic Bacteria in Soft Agar: Role of Gel Concentration

PubMed Central

Croze, Ottavio A.; Ferguson, Gail P.; Cates, Michael E.; Poon, Wilson C.K.

2011-01-01

We study the migration of chemotactic wild-type Escherichia coli populations in semisolid (soft) agar in the concentration range C = 0.15–0.5% (w/v). For C≲0.35%, expanding bacterial colonies display characteristic chemotactic rings. At C = 0.35%, however, bacteria migrate as broad circular bands rather than sharp rings. These are growth/diffusion waves arising because of suppression of chemotaxis by the agar and have not been previously reported experimentally to our knowledge. For C = 0.4–0.5%, expanding colonies do not span the depth of the agar and develop pronounced front instabilities. The migration front speed is weakly dependent on agar concentration at C < 0.25%, but decreases sharply above this value. We discuss these observations in terms of an extended Keller-Segel model for which we derived novel transport parameter expressions accounting for perturbations of the chemotactic response by collisions with the agar. The model makes it possible to fit the observed front speed decay in the range C = 0.15–0.35%, and its solutions qualitatively reproduce the observed transition from chemotactic to growth/diffusion bands. We discuss the implications of our results for the study of bacteria in porous media and for the design of improved bacteriological chemotaxis assays. PMID:21806920

MicroRNA-124 Controls the Proliferative, Migratory, and Inflammatory Phenotype of Pulmonary Vascular Fibroblasts

PubMed Central

Wang, Daren; Zhang, Zhang; Li, Min; Frid, Maria G.; Flockton, Amanda R.; McKeon, B. Alexandre; Yeager, Michael E.; Fini, Mehdi A.; Morrell, Nicholas W.; Pullamsetti, Soni S.; Velegala, Sivareddy; Seeger, Werner; McKinsey, Timothy A.; Sucharov, Carmen C.; Stenmark, Kurt R.

2014-01-01

Rationale Pulmonary hypertensive remodeling is characterized by excessive proliferation, migration, and proinflammatory activation of adventitial fibroblasts. In culture, fibroblasts maintain a similar activated phenotype. The mechanisms responsible for generation/maintenance of this phenotype remain unknown. Objective We hypothesized that aberrant expression of microRNA-124 (miR-124) regulates this activated fibroblast phenotype and sought to determine the signaling pathways through which miR-124 exerts effects. Methods and Results We detected significant decreases in miR-124 expression in fibroblasts isolated from calves and humans with severe pulmonary hypertension. Overexpression of miR-124 by mimic transfection significantly attenuated proliferation, migration, and monocyte chemotactic protein-1 expression of hypertensive fibroblasts, whereas anti–miR-124 treatment of control fibroblasts resulted in their increased proliferation, migration, and monocyte chemotactic protein-1 expression. Furthermore, the alternative splicing factor, polypyrimidine tract–binding protein 1, was shown to be a direct target of miR-124 and to be upregulated both in vivo and in vitro in bovine and human pulmonary hypertensive fibroblasts. The effects of miR-124 on fibroblast proliferation were mediated via direct binding to the 3′ untranslated region of polypyrimidine tract–binding protein 1 and subsequent regulation of Notch1/phosphatase and tensin homolog/FOXO3/p21Cip1 and p27Kip1 signaling. We showed that miR-124 directly regulates monocyte chemotactic protein-1 expression in pulmonary hypertension/idiopathic pulmonary arterial hypertension fibroblasts. Furthermore, we demonstrated that miR-124 expression is suppressed by histone deacetylases and that treatment of hypertensive fibroblasts with histone deacetylase inhibitors increased miR-124 expression and decreased proliferation and monocyte chemotactic protein-1 production. Conclusions Stable decreases in miR-124 expression contribute to an epigenetically reprogrammed, highly proliferative, migratory, and inflammatory phenotype of hypertensive pulmonary adventitial fibroblasts. Thus, therapies directed at restoring miR-124 function, including histone deacetylase inhibitors, should be investigated. PMID:24122720

A simple expression for quantifying bacterial chemotaxis using capillary assay data: application to the analysis of enhanced chemotactic responses from growth-limited cultures.

PubMed

Ford, R M; Lauffenburger, D A

1992-05-01

An individual cell-based mathematical model of Rivero et al. provides a framework for determining values of the chemotactic sensitivity coefficient chi 0, an intrinsic cell population parameter that characterizes the chemotactic response of bacterial populations. This coefficient can theoretically relate the swimming behavior of individual cells to the resulting migration of a bacterial population. When this model is applied to the commonly used capillary assay, an approximate solution can be obtained for a particular range of chemotactic strengths yielding a very simple analytical expression for estimating the value of chi 0, [formula: see text] from measurements of cell accumulation in the capillary, N, when attractant uptake is negligible. A0 and A infinity are the dimensionless attractant concentrations initially present at the mouth of the capillary and far into the capillary, respectively, which are scaled by Kd, the effective dissociation constant for receptor-attractant binding. D is the attractant diffusivity, and mu is the cell random motility coefficient. NRM is the cell accumulation in the capillary in the absence of an attractant gradient, from which mu can be determined independently as mu = (pi/4t)(NRM/pi r2bc)2, with r the capillary tube radius and bc the bacterial density initially in the chamber. When attractant uptake is significant, a slightly more involved procedure requiring a simple numerical integration becomes necessary. As an example, we apply this approach to quantitatively characterize, in terms of the chemotactic sensitivity coefficient chi 0, data from Terracciano indicating enhanced chemotactic responses of Escherichia coli to galactose when cultured under growth-limiting galactose levels in a chemostat.

IN VITRO AND IN VIVO ACTIVITY OF A LYMPHOCYTE AND IMMUNE COMPLEX-DEPENDENT CHEMOTACTIC FACTOR FOR EOSINOPHILS

PubMed Central

Cohen, Stanley; Ward, Peter A.

1971-01-01

When cultured in the presence of specific antigen, lymphocytes from delayed-hypersensitive guinea pigs release a number of biologically active substances into the culture medium. Such active supernatants can react with immune complexes in vitro to generate a factor which is chemotactic for eosinophils. The factor involved is unique, since previously described chemotactic factors for other cell types require for their generation either immune complexes or substances released into lymphocyte culture, but not both. In the case of the eosinophil chemotactic factor, the interaction between the substance elaborated by the lymphocytes and the immune complexes appears to be specific in that the immune complexes must contain the same antigen as that used to activate the lymphocyte cultures. Although this factor was generated in an in vitro system, it has been shown to possess in vivo as well as in vitro activity. It is therefore possible that this factor may be of biological significance in situations where eosinophils are participants in inflammatory or immunologic reactions. PMID:5099667

Conformational suppression of inter-receptor signaling defects

PubMed Central

Ames, Peter; Parkinson, John S.

2006-01-01

Motile bacteria follow gradients of attractant and repellent chemicals with high sensitivity. Their chemoreceptors are physically clustered, which may enable them to function as a cooperative array. Although native chemoreceptor molecules are typically transmembrane homodimers, they appear to associate through their cytoplasmic tips to form trimers of dimers, which may be an important architectural element in the assembly and operation of receptor clusters. The five receptors of Escherichia coli that mediate most of its chemotactic and aerotactic behaviors have identical trimer contact residues and have been shown by in vivo crosslinking methods to form mixed trimers of dimers. Mutations at the trimer contact sites of Tsr, the serine chemoreceptor, invariably abrogate Tsr function, but some of those lesions (designated Tsr*) are epistatic and block the function of heterologous chemoreceptors. We isolated and characterized mutations (designated Tar⋀) in the aspartate chemoreceptor that restored function to Tsr* receptors. The suppressors arose at or near the Tar trimer contact sites and acted in an allele-specific fashion on Tsr* partners. Alone, many Tar⋀ receptors were unable to mediate chemotactic responses to aspartate, but all formed clusters with varying efficiencies. Most of those Tar⋀ receptors were epistatic to WT Tsr, but some regained Tar function in combination with a suppressible Tsr* partner. Tar⋀–Tsr* suppression most likely occurs through compensatory changes in the conformation or dynamics of a mixed receptor signaling complex, presumably based on trimer-of-dimer interactions. These collaborative teams may be responsible for the high-gain signaling properties of bacterial chemoreceptors. PMID:16751275

Colloidal silver nanoparticles/rhamnolipid (SNPRL) composite as novel chemotactic antibacterial agent.

PubMed

Bharali, P; Saikia, J P; Paul, S; Konwar, B K

2013-10-01

The antibacterial activity of silver nanoparticles and rhamnolipid are well known individually. In the present research, antibacterial and chemotactic activity due to colloidal silver nanoparticles (SNP), rhamnolipid (RL) and silver nanoparticles/rhamnolipid composite (SNPRL) were evaluated using Staphylococcus aureus (MTCC3160), Escherichia coli (MTCC40), Pseudomonas aeruginosa (MTCC8163) and Bacillus subtilis (MTCC441) as test strains. Further, the SNPRL nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The observation clearly indicates that SNPRL shows prominent antibacterial and chemotactic activity in comparison to all of its individual precursor components. Copyright © 2013 Elsevier B.V. All rights reserved.

Transverse Chemotactic Migration of Bacteria from High to Low Permeability Regions in a Dual Permeability Porous Microfluidic Device

NASA Astrophysics Data System (ADS)

Singh, R.; Olson, M. S.

2011-12-01

Low permeability regions sandwiched between high permeability regions such as clay lenses are difficult to treat using conventional treatment methods. Trace concentrations of contaminants such as non-aqueous phase liquids (NAPLs) remain trapped in these regions and over the time diffuse out into surrounding water thereby acting as a long term source of groundwater contamination. Bacterial chemotaxis (directed migration toward a contaminant source), may be helpful in enhancing bioremediation of such contaminated sites. This study is focused on simulating a two-dimensional dual-permeability groundwater contamination scenario using microfluidic devices and evaluating transverse chemotactic migration of bacteria from high to low permeability regions. A novel bi-layer polydimethylsiloxane (PDMS) microfluidic device was fabricated using photolithography and soft lithography techniques to simulate contamination of a dual- permeability region due to leakage from an underground storage tank into a low permeability region. This device consists of a porous channel through which a bacterial suspension (Escherchia Coli HCB33) is flown and another channel for injecting contaminant/chemo-attractant (DL-aspertic acid) into the porous channel. The pore arrangement in the porous channel contains a 2-D low permeability region surrounded by high permeability regions on both sides. Experiments were performed under chemotactic and non-chemotactic (replacing attractant with buffer solution in the non porous channel) conditions. Images were captured in transverse pore throats at cross-sections 4.9, 9.8, and 19.6 mm downstream from the attractant injection point and bacteria were enumerated in the middle of each pore throat. Bacterial chemotaxis was quantified in terms of the change in relative bacterial counts in each pore throat at cross-sections 9.8 and 19.6 mm with respect to counts at the cross-section at 4.9 mm. Under non-chemotactic conditions, relative bacterial count was observed to decrease at 9.8 mm and 19.6 mm cross-sections in low permeability regions due to dilution with the injectate from the non-porous channel (Figure 1). However, relative bacterial counts increased in the low permeability region at both downstream cross-sections under chemotactic conditions. A large increase in relative bacterial count in the pore throats just outside the low permeability region was also observed at both cross-sections (Figure 1). The bacterial chemotactic response was observed to decrease linearly with increasing Darcy velocity and at flow rate 0.220 mm/s the chemotactic effect was offset by the advective flow in the porous channel.

The Anti-Inflammatory Cytokine Interleukin-19 Is Expressed in and Angiogenic for Human Endothelial Cells

PubMed Central

Jain, Surbhi; Gabunia, Khatuna; Kelemen, Sheri E.; Panetti, Tracee S.; Autieri, Michael V.

2010-01-01

OBJECTIVE The expression and effects of anti-inflammatory interleukins on endothelial cell (EC) activation and development of angiogenesis is uncharacterized. The purpose of this study is to characterize the expression and function of Interleukin-19 (IL-19), a recently described Th2 anti-inflammatory interleukin on EC pathophysiology. METHODS and RESULTS We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal human coronary endothelium, and can be induced in cultured human EC by serum and bFGF. IL-19 is mitogenic, chemotactic, and promotes cell EC spreading. IL-19 activates the signaling proteins STAT3, p44/42, and Rac1. In functional ex vivo studies, IL-19 promotes cord-like structure formation of cultured EC and also enhances microvessel sprouting in the mouse aortic ring assay. IL-19 induces tube formation in matrigel plugs in vivo. CONCLUSIONS These data are the first to report expression of the anti-inflammatory interleukin IL-19 in EC, and the first to indicate that IL-19 is mitogenic and chemotactic for EC, and can induce the angiogenic potential of EC. PMID:20966397

Squid-derived chitin oligosaccharides are a chemotactic signal during colonization by Vibrio fischeri.

PubMed

Mandel, Mark J; Schaefer, Amy L; Brennan, Caitlin A; Heath-Heckman, Elizabeth A C; Deloney-Marino, Cindy R; McFall-Ngai, Margaret J; Ruby, Edward G

2012-07-01

Chitin, a polymer of N-acetylglucosamine (GlcNAc), is noted as the second most abundant biopolymer in nature. Chitin serves many functions for marine bacteria in the family Vibrionaceae ("vibrios"), in some instances providing a physical attachment site, inducing natural genetic competence, and serving as an attractant for chemotaxis. The marine luminous bacterium Vibrio fischeri is the specific symbiont in the light-emitting organ of the Hawaiian bobtail squid, Euprymna scolopes. The bacterium provides the squid with luminescence that the animal uses in an antipredatory defense, while the squid supports the symbiont's nutritional requirements. V. fischeri cells are harvested from seawater during each host generation, and V. fischeri is the only species that can complete this process in nature. Furthermore, chitin is located in squid hemocytes and plays a nutritional role in the symbiosis. We demonstrate here that chitin oligosaccharides produced by the squid host serve as a chemotactic signal for colonizing bacteria. V. fischeri uses the gradient of host chitin to enter the squid light organ duct and colonize the animal. We provide evidence that chitin serves a novel function in an animal-bacterial mutualism, as an animal-produced bacterium-attracting synomone.

ALTERATIONS OF MACROPHAGE FUNCTIONS BY MEDIATORS FROM LYMPHOCYTES

PubMed Central

Nathan, Carl F.; Karnovsky, Manfred L.; David, John R.

1971-01-01

Sensitized lymphocytes were incubated in vitro with the specific antigen Supernatants from these cultures were chromatographed on Sephadex G-100 columns. Supernatant fractions containing MIF, chemotactic factor, and lymphotoxin, but free of antigen and antibody, were incubated with normal peritoneal exudate macrophages. Macrophage adherence, phagocytosis, spreading, motility, and direct hexose monophosphate oxidation were enhanced, while protein synthesis was unaffected. Thus, antigen-stimulated lymphocytes secrete a factor or factors which enhance certain macrophage functions. Implications for models of cellular immunity and cellular hypersensitivity are discussed. PMID:5576335

Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet

USDA-ARS?s Scientific Manuscript database

Obesity is a risk factor for cancer. Adipose tissue produces pro-inflammatory adipokines that contribute obesity-related malignant progression. This study investigated the effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in male C57...

Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

NASA Astrophysics Data System (ADS)

Unachukwu, Uchenna John; Warren, Alice; Li, Ze; Mishra, Shawn; Zhou, Jing; Sauane, Moira; Lim, Hyungsik; Vazquez, Maribel; Redenti, Stephen

2016-03-01

To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

Chemotactic and hydrodynamic effects on collective dynamics of self-diffusiophoretic Janus motors

NASA Astrophysics Data System (ADS)

Huang, Mu-Jie; Schofield, Jeremy; Kapral, Raymond

2017-12-01

Collective motion in nonequilibrium steady state suspensions of self-propelled Janus motors driven by chemical reactions can arise due to interactions coming from direct intermolecular forces, hydrodynamic flow effects, or chemotactic effects mediated by chemical gradients. The relative importance of these interactions depends on the reactive characteristics of the motors, the way in which the system is maintained in a steady state, and properties of the suspension, such as the volume fraction. From simulations of a microscopic hard collision model for the interaction of fluid particles with the Janus motor we show that dynamic cluster states exist and determine the interaction mechanisms that are responsible for their formation. The relative importance of chemotactic and hydrodynamic effects is identified by considering a microscopic model in which chemotactic effects are turned off while the full hydrodynamic interactions are retained. The system is maintained in a steady state by means of a bulk reaction in which product particles are reconverted into fuel particles. The influence of the bulk reaction rate on the collective dynamics is also studied.

Motility and Adhesiveness in Human Neutrophils

PubMed Central

Smith, C. Wayne; Hollers, James C.; Patrick, Richard A.; Hassett, Clare

1979-01-01

Human peripheral blood neutrophils (PMN) obtained from healthy adults were examined in vitro with techniques adapted to assess the effects of chemotactic factors (CF) on cellular configuration and adhesiveness. The results were compared with those that use certain conventional techniques for assessing chemotaxis and chemokinesis. Exposure of PMN to N-formyl-l-methionyl-l-phenylalanine (f-Met-Phe), zymosan-activated serum, bacterial chemotactic factor, or a low molecular weight chemotactic factor from activated serum (C5a) in the absence of a gradient resulted in a change in cellular shape from a spherical to a polarized configuration in a high percentage of cells. This occurred rapidly in suspension, under conditions designed to exclude a role for cell adhesiveness, and was reversible upon removal of the CF. Restimulation of cells with the CF resulted in reappearance of the polarized configuration to the same extent as on initial stimulation with one exception: f-Met-Phe pretreated cells failed to respond to f-Met-Phe, though they responded fully to the other CF. Each CF caused a significant increase in PMN attachment to protein-coated glass. This enhanced adhesiveness was not reversible upon removal of the CF when the cells were treated under conditions shown to produce chemotactic deactivation. Cells treated under these conditions also exhibited significantly reduced motility on glass and in micropore filters in the absence of a gradient of CF. Bacterial chemotactic factor, even at high concentrations, failed to produce deactivation and did not cause a sustained enhancement of adhesiveness. Images PMID:372238

Active Brownian agents with concentration-dependent chemotactic sensitivity.

PubMed

Meyer, Marcel; Schimansky-Geier, Lutz; Romanczuk, Pawel

2014-02-01

We study a biologically motivated model of overdamped, autochemotactic Brownian agents with concentration-dependent chemotactic sensitivity. The agents in our model move stochastically and produce a chemical ligand at their current position. The ligand concentration obeys a reaction-diffusion equation and acts as a chemoattractant for the agents, which bias their motion towards higher concentrations of the dynamically altered chemical field. We explore the impact of concentration-dependent response to chemoattractant gradients on large-scale pattern formation, by deriving a coarse-grained macroscopic description of the individual-based model, and compare the conditions for emergence of inhomogeneous solutions for different variants of the chemotactic sensitivity. We focus primarily on the so-called receptor-law sensitivity, which models a nonlinear decrease of chemotactic sensitivity with increasing ligand concentration. Our results reveal qualitative differences between the receptor law, the constant chemotactic response, and the so-called log law, with respect to stability of the homogeneous solution, as well as the emergence of different patterns (labyrinthine structures, clusters, and bubbles) via spinodal decomposition or nucleation. We discuss two limiting cases, where the model can be reduced to the dynamics of single species: (I) the agent density governed by a density-dependent effective diffusion coefficient and (II) the ligand field with an effective bistable, time-dependent reaction rate. In the end, we turn to single clusters of agents, studying domain growth and determining mean characteristics of the stationary inhomogeneous state. Analytical results are confirmed and extended by large-scale GPU simulations of the individual based model.

Migration of Chemotactic Bacteria Transverse to Flow in Response to a Benzoate Source Plume Created in a Saturated Sand-Packed Microcosm

NASA Astrophysics Data System (ADS)

Ford, R.; Boser, B.

2012-12-01

Bioremediation processes depend on contact between microbial populations and the groundwater contaminants that they biodegrade. Chemotaxis, the ability of bacteria to sense a chemical gradient and swim preferentially toward locations of higher concentration, can enhance the transport of bacteria toward contaminant sources that may not be readily accessible by advection and dispersion alone. A two-dimensional rectangular-shaped microcosm packed with quartz sand was used to quantify the effect of chemotaxis on the migration of bacteria within a saturated model aquifer system. Artificial groundwater was pumped through the microcosm at a rate of approximately 1 m/day. A plume of sodium benzoate was created by continuous injection into an upper port of the microcosm to generate a chemical gradient in the vertical direction transverse to flow. Chemotactic bacteria, Pseudomonas putida F1, or the nonchemotactic mutant, P. putida F1 CheA, were injected with a conservative tracer in a port several centimeters below the benzoate position. As the injectates traversed the one-meter length of the microcosm, samples were collected from a dozen effluent ports to determine vertical concentration distributions for the bacteria, benzoate and tracer. A moment analysis was implemented to estimate the center of mass, variance, and skewness of the concentration profiles. The transverse dispersion coefficient and the transverse dispersivity for chemotactic and nonchemotactic bacteria were also evaluated. Experiments performed with a continuous injection of bacteria showed that the center of mass for chemotactic bacteria was closer to the benzoate source on average than the nonchemotactic control (relative to the conservative tracer). These results demonstrated that chemotaxis can increase bacterial transport toward contaminants, potentially enhancing the effectiveness of in situ bioremediation. Experiments with 2 cm and 3 cm spacing between bacteria and benzoate injection locations were performed to explore the relationship between the exposure time of the bacteria to benzoate and the transverse migration of bacteria due to chemotaxis. Experimentally determined transport parameters were then used as input to a two-dimensional mathematical model for bacterial transport. Model results showed the shift in center of mass for chemotactic bacteria was greater for 2 cm and 3 cm spacing than for 4 cm spacing for a given chemotactic sensitivity coefficient value, which showed that an increase in the exposure time of the bacteria to the model contaminant benzoate increased the transverse migration of bacteria. Modeling was used to test the effects of changing the chemotactic sensitivity coefficient and the chemotaxis receptor constant at three different bacteria and benzoate separation distances: 2 cm, 3 cm, and 4 cm. Mathematical models from this work can be applied to future field-scale studies to select design parameters that maximize transverse migration of chemotactic bacteria.

Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

PubMed

Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

2012-01-01

Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.

Threshold levels of ERK activation for chemotactic migration differ for NGF and EGF in rat pheochromocytoma PC12 cells.

PubMed

Ho, W C; Uniyal, S; Zhou, H; Morris, V L; Chan, B M C

2005-03-01

In a previous study, we show that stimulation of chemotaxis in rat pheochromocytoma PC12 cells by nerve growth factor (NGF) and epidermal growth factor (EGF) requires activation of the RAS-ERK signaling pathway. In this study, we compared the threshold levels of ERK activation required for EGF and NGF-stimulated chemotaxis in PC12 cells. The threshold ERK activity required for NGF to stimulate chemotaxis was approximately 30% lower than that for EGF. PD98059 treatment inhibited EGF stimulation of growth and chemotaxis; however, stimulation of chemotaxis required an EGF concentration approximately 10 times higher than for stimulation of PC12 cell growth. Thus, ERK-dependent cellular functions can be differentially elicited by the concentration of EGF. Also, treatment of PC12 cells with the PI3-K inhibitor LY294002 reduced ERK activation by NGF; thus, higher NGF concentrations were required to initiate chemotaxis and to achieve the same maximal chemotactic response seen in untreated PC12 cells. Therefore, the threshold NGF concentration to stimulate chemotaxis could be adjusted by the crosstalk between the ERK and PI3-K pathways, and the contributions of PI3-K and ERK to signal chemotaxis varied with the concentrations of NGF used. In comparison, LY294002 treatment had no effect on ERK activation by EGF, but the chemotactic response was reduced at all the concentrations of EGF tested indicating that NGF and EGF differed in the utilization of ERK and PI3-K to signal chemotaxis in PC12 cells.

BRE facilitates skeletal muscle regeneration by promoting satellite cell motility and differentiation

PubMed Central

Xiao, Lihai; Lee, Kenneth Ka Ho

2016-01-01

ABSTRACT The function of the Bre gene in satellite cells was investigated during skeletal muscle regeneration. The tibialis anterior leg muscle was experimentally injured in Bre knockout mutant (BRE-KO) mice. It was established that the accompanying muscle regeneration was impaired as compared with their normal wild-type counterparts (BRE-WT). There were significantly fewer pax7+ satellite cells and smaller newly formed myofibers present in the injury sites of BRE-KO mice. Bre was required for satellite cell fusion and myofiber formation. The cell fusion index and average length of newly-formed BRE-KO myofibers were found to be significantly reduced as compared with BRE-WT myofibers. It is well established that satellite cells are highly invasive which confers on them the homing ability to reach the muscle injury sites. Hence, we tracked the migratory behavior of these cells using time-lapse microscopy. Image analysis revealed no difference in directionality of movement between BRE-KO and BRE-WT satellite cells but there was a significant decrease in the velocity of BRE-KO cell movement. Moreover, chemotactic migration assays indicated that BRE-KO satellite cells were significantly less responsive to chemoattractant SDF-1α than BRE-WT satellite cells. We also established that BRE normally protects CXCR4 from SDF-1α-induced degradation. In sum, BRE facilitates skeletal muscle regeneration by enhancing satellite cell motility, homing and fusion. PMID:26740569

Trends in the design of nerve guidance channels in peripheral nerve tissue engineering.

PubMed

Chiono, Valeria; Tonda-Turo, Chiara

2015-08-01

The current trend of peripheral nerve tissue engineering is the design of advanced nerve guidance channels (NGCs) acting as physical guidance for regeneration of nerves across lesions. NGCs should present multifunctional properties aiming to direct the sprouting of axons from the proximal nerve end, to concentrate growth factors secreted by the injured nerve ends, and to reduce the ingrowth of scar tissue into the injury site. A critical aspect in the design of NGCs is conferring them the ability to provide topographic, chemotactic and haptotactic cues that lead to functional nerve regeneration thus increasing the axon growth rate and avoiding or minimizing end-organ (e.g. muscle) atrophy. The present work reviews the recent state of the art in NGCs engineering and defines the external guide and internal fillers structural and compositional requirements that should be satisfied to improve nerve regeneration, especially in the case of large gaps (>2 cm). Techniques for NGCs fabrication were described highlighting the innovative approaches direct to enhance the regeneration of axon stumps compared to current clinical treatments. Furthermore, the possibility to apply stem cells as internal cues to the NGCs was discussed focusing on scaffold properties necessary to ensure cell survival. Finally, the optimized features for NGCs design were summarized showing as multifunctional cues are needed to produce NGCs having improved results in clinics. Copyright © 2015 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, G.E.

When intact Arbacia punctulata spermatozoa are exposed to solubilized egg jelly, the electrophoretic mobility of an abundant sperm flagellar membrane protein changes from an apparent molecular mass of 160 kDa to 150 kDa. A. punctulata spermatozoa can be labeled in vivo with /sup 32/P-labeled cells it was demonstrated that the mobility shift of the 160-kDa protein is due to dephosphorylation. The peptide resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH/sub 2/) is the component of egg jelly which is responsible for inducing the dephosphorylation. The 160/150-kdal sperm membrane protein has been purified to homogeneity by affinity chromatography on concanavalin A-agarose, and identified as sperm guanylate cyclase.more » The enzymatic activity of the guanylate cyclase is tightly coupled to its phosphorylation state. Resact has been shown to act as a potent chemoattractant for A. punctulata spermatozoa. The chemotactic response is concentration-dependent, is abolished by pretreatment of the spermatozoa with resact, and shows an absolute requirement for external calcium. This work represents the first demonstration of animal sperm chemotaxis in response to a precisely-defined molecule of egg origin. The results established a new, biologically meaningful function for resact, and may implicate sperm guanylate cyclase and cGMP in flagellar function and the chemotactic response.« less

Chemotactic cell trapping in controlled alternating gradient fields

PubMed Central

Meier, Börn; Zielinski, Alejandro; Weber, Christoph; Arcizet, Delphine; Youssef, Simon; Franosch, Thomas; Rädler, Joachim O.; Heinrich, Doris

2011-01-01

Directed cell migration toward spatio-temporally varying chemotactic stimuli requires rapid cytoskeletal reorganization. Numerous studies provide evidence that actin reorganization is controlled by intracellular redistribution of signaling molecules, such as the PI4,5P2/PI3,4,5P3 gradient. However, exploring underlying mechanisms is difficult and requires careful spatio-temporal control of external chemotactic stimuli. We designed a microfluidic setup to generate alternating chemotactic gradient fields for simultaneous multicell exposure, greatly facilitating statistical analysis. For a quantitative description of intracellular response dynamics, we apply alternating time sequences of spatially homogeneous concentration gradients across 300 μm, reorienting on timescales down to a few seconds. Dictyostelium discoideum amoebae respond to gradient switching rates below 0.02 Hz by readapting their migration direction. For faster switching, cellular repolarization ceases and is completely stalled at 0.1 Hz. In this “chemotactically trapped” cell state, external stimuli alternate faster than intracellular feedback is capable to respond by onset of directed migration. To investigate intracellular actin cortex rearrangement during gradient switching, we correlate migratory cell response with actin repolymerization dynamics, quantified by a fluorescence distribution moment of the GFP fusion protein LimEΔcc. We find two fundamentally different cell polarization types and we could reveal the role of PI3-Kinase for cellular repolarization. In the early aggregation phase, PI3-Kinase enhances the capability of D. discoideum cells to readjust their polarity in response to spatially alternating gradient fields, whereas in aggregation competent cells the effect of PI3-Kinase perturbation becomes less relevant. PMID:21709255

Tumour related inhibition of macrophage chemotaxis in patients with colon cancer.

PubMed Central

Hermanowicz, A; Gibson, P R; Jewell, D P

1987-01-01

The chemotactic migration in vitro of peripheral blood, intestinal mucosal, and mesenteric lymph node mononuclear cells has been assessed in patients with colorectal carcinoma. Peripheral blood mononuclear cells of patients exhibited normal chemotaxis. For control patients with non-malignant, non-inflammatory intestinal disease, the chemotaxis of mucosal mononuclear cells was similar to that of autologous peripheral blood mononuclear cells. The chemotactic migration of mucosal mononuclear cells, however, isolated distant from a colon cancer was less than that of autologous peripheral blood mononuclear cells. Chemotactic migration was progressively impaired with increasing closeness to the tumour itself. Chemotaxis of mucosal mononuclear cell was independent of the site of tumour and the Dukes' grading. Mononuclear cells from mesenteric lymph nodes, however, exhibited impaired migration only in patients with Dukes' C tumours. Supernatants of the collagenase digestion of either tumour or adjacent mucosa contained macrophage directed inhibitors of chemotaxis and these inhibitors were not produced by tumour mononuclear cells. The presence of such inhibitors in the digestion supernatants and the demonstration that proximity to the tumour was associated with impaired mononuclear cell motility suggest that the production of macrophage directed chemotactic inhibitors is by colon cancer cells and that this may be occurring in vivo. PMID:3583069

C/EBP epsilon directs granulocytic versus monocytic lineage determination and confers chemotactic function via Hlx

PubMed Central

Halene, Stephanie; Gaines, Peter; Sun, Hong; Zibello, Theresa; Lin, Sharon; Khanna-Gupta, Arati; Williams, Simon C.; Perkins, Archibald; Krause, Diane; Berliner, Nancy

2010-01-01

Objective Mutations in the C/EBPε gene have been identified in the cells of patients with neutrophil specific granule deficiency (SGD), a rare congenital disorder marked by recurrent bacterial infections. Their neutrophils, in addition to lacking specific granules required for normal respiratory burst activity, also lack normal phagocytosis and chemotaxis. Although the SGD phenotype has been replicated in C/EBPε−/− (KO) mice, the mechanisms by which C/EBPε mutations act to decrease neutrophil function are not entirely clear. Methods In order to determine the role of C/EBPε in neutrophil differentiation and migration, we generated immortalized progenitor cell lines from C/EBPε KO and wild type (WT) mice and performed expression and flow cytometric analysis and functional studies. Results Expression of lineage specific cell surface antigens on our in vitro differentiated cell lines revealed persistent expression of monocytic markers on KO granulocytes. We verified this in primary murine peripheral blood and bone marrow cells. In addition, KO BM had an increase in immature myeloid precursors at the common myeloid progenitor (CMP) and granulocyte monocyte progenitor (GMP) level suggesting a critical role for C/EBPε not only in granulocyte maturation beyond the promyelocyte stage, but also in the monocyte/granulocyte lineage decision. We found that restoration of Hlx (H2.0-like homeo box 1) expression, which was decreased in C/EBPε KO cells, rescued chemotaxis, but not the other defects of C/EBPε KO neutrophils. Summary We show two new regulatory functions of C/EBPε in myelopoiesis: in the absence of C/EBPε, there is not only incomplete differentiation of granulocytes, but myelopoiesis is disrupted with the appearance of an intermediate cell type with monocyte and granulocyte features, and the neutrophils have abnormal chemotaxis. Restoration of expression of Hlx provides partial recovery of function; it has no effect on neutrophil maturation, but can completely ameliorate the chemotaxis defect in C/EBPe KO cells. PMID:19925846

Using optical tweezers to examine the chemotactic force to a single inflammatory cell--eosinophil stimulated by chemoattractants prepared from Toxocara Canis larvae

NASA Astrophysics Data System (ADS)

Shih, Po-Chen; Su, Yi-Jr; Chen, Ke-Min; Jen, Lin-Ni; Liu, Cheng-tzu; Hsu, Long

2005-08-01

Granulocytes are a group of white blood cells belonging to the innate immune system in human and in murine in which eosinophils play an important role in worm infection-induced inflammation. The migration of these cells is well characterized and has been separated into four steps: rolling, adhesion, transendothelial migration, and chemotaxis, however, the physical characteristics of the chemotactic force to eosinophils from worm component remain largely unknown. Note that optical tweezers are featured in the manipulation of a single cell and the measurement of biological forces. Therefore, we propose to use optical tweezers to examine the chemotactic force to a eosinophil from a T. canis lavae preparation in terms of distance during the migration of eosinophil.

Monocyte chemotactic protein-1 attenuates and high-fat diet exacerbates bone loss in mice with pulmonary metastasis of Lewis lung carcinoma

USDA-ARS?s Scientific Manuscript database

Bone can be adversely affected by obesity and cancer-associated complications including wasting. The objective of this study was to determine whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects found in male C57BL/6 mice with Lewis lung...

Human Platelets Exhibit Chemotaxis using Functional N-Formyl Peptide Receptors

DTIC Science & Technology

2005-01-01

activated phagocytes. Therefore, we examined the chemotactic migration of platelets qualita- tively by videomicroscopy . Platelets in medium were al- lowed...significantly decreased M. Czapiga et al. /Experimental Hematology 33 (2005) 73–84 79Figure 3. Videomicroscopy of human platelets in response to formyl...selected platelets during videomicroscopy from the time of the addition of fMLF (104 M in 1 µL) or PBS. Movement between markers represents 10 frames

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

NASA Astrophysics Data System (ADS)

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.

Sperm from sneaker male squids exhibit chemotactic swarming to CO₂.

PubMed

Hirohashi, Noritaka; Alvarez, Luis; Shiba, Kogiku; Fujiwara, Eiji; Iwata, Yoko; Mohri, Tatsuma; Inaba, Kazuo; Chiba, Kazuyoshi; Ochi, Hiroe; Supuran, Claudiu T; Kotzur, Nico; Kakiuchi, Yasutaka; Kaupp, U Benjamin; Baba, Shoji A

2013-05-06

Behavioral traits of sperm are adapted to the reproductive strategy that each species employs. In polyandrous species, spermatozoa often form motile clusters, which might be advantageous for competing with sperm from other males. Despite this presumed advantage for reproductive success, little is known about how sperm form such functional assemblies. Previously, we reported that males of the coastal squid Loligo bleekeri produce two morphologically different euspermatozoa that are linked to distinctly different mating behaviors. Consort and sneaker males use two distinct insemination sites, one inside and one outside the female's body, respectively. Here, we show that sperm release a self-attracting molecule that causes only sneaker sperm to swarm. We identified CO2 as the sperm chemoattractant and membrane-bound flagellar carbonic anhydrase as its sensor. Downstream signaling results from the generation of extracellular H(+), intracellular acidosis, and recovery from acidosis. These signaling events elicit Ca(2+)-dependent turning behavior, resulting in chemotactic swarming. These results illuminate the bifurcating evolution of sperm underlying the distinct fertilization strategies of this species. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemotactic signal integration in bacteria.

PubMed Central

Khan, S; Spudich, J L; McCray, J A; Trentham, D R

1995-01-01

Chemotactic signaling in Escherichia coli involves transmission of both negative and positive signals. In order to examine mechanisms of signal processing, behavioral responses to dual inputs have been measured by using photoactivable "caged" compounds, computer video analysis, and chemoreceptor deletion mutants. Signaling from Tar and Tsr, two receptors that sense amino acids and pH, was studied. In a Tar deletion mutant the photoactivated release of protons, a Tsr repellent, and of serine, a Tsr attractant, in separate experiments at pH 7.0 resulted in tumbling (negative) or smooth-swimming (positive) responses in ca. 50 and 140 ms, respectively. Simultaneous photorelease of protons and serine resulted in a single tumbling or smooth-swimming response, depending on the relative amounts of the two effectors. In contrast, in wild-type E. coli, proton release at pH 7.0 resulted in a biphasic response that was attributed to Tsr-mediated tumbling followed by Tar-mediated smooth-swimming. In wild-type E. coli at more alkaline pH values the Tar-mediated signal was stronger than the Tsr signal, resulting in a strong smooth-swimming response preceded by a diminished tumbling response. These observations imply that (i) a single receptor time-averages the binding of different chemotactic ligands generating a single response; (ii) ligand binding to different receptors can result in a nonintegrated response with the tumbling response preceding the smooth-swimming response; (iii) however, chemotactic signals of different intensities derived from different receptors can also result in an apparently integrated response; and (iv) the different chemotactic responses to protons at neutral and alkaline pH may contribute to E. coli migration toward neutrality. Images Fig. 6 PMID:7568212

Bacterial chemotaxis along vapor-phase gradients of naphthalene.

PubMed

Hanzel, Joanna; Harms, Hauke; Wick, Lukas Y

2010-12-15

The role of bacterial growth and translocation for the bioremediation of organic contaminants in the vadose zone is poorly understood. Whereas air-filled pores restrict the mobility of bacteria, diffusion of volatile organic compounds in air is more efficient than in water. Past research, however, has focused on chemotactic swimming of bacteria along gradients of water-dissolved chemicals. In this study we tested if and to what extent Pseudomonas putida PpG7 (NAH7) chemotactically reacts to vapor-phase gradients forming above their swimming medium by the volatilization from a spot source of solid naphthalene. The development of an aqueous naphthalene gradient by air-water partitioning was largely suppressed by means of activated carbon in the agar. Surprisingly, strain PpG7 was repelled by vapor-phase naphthalene although the steady state gaseous concentrations were 50-100 times lower than the aqueous concentrations that result in positive chemotaxis of the same strain. It is thus assumed that the efficient gas-phase diffusion resulting in a steady, and possibly toxic, naphthalene flux to the cells controlled the chemotactic reaction rather than the concentration to which the cells were exposed. To our knowledge this is the first demonstration of apparent chemotactic behavior of bacteria in response to vapor-phase effector gradients.

Endothelial-derived interleukin-6 induces cancer stem cell motility by generating a chemotactic gradient towards blood vessels.

PubMed

Kim, Hong Sun; Chen, Yu-Chih; Nör, Felipe; Warner, Kristy A; Andrews, April; Wagner, Vivian P; Zhang, Zhaocheng; Zhang, Zhixiong; Martins, Manoela D; Pearson, Alexander T; Yoon, Euisik; Nör, Jacques E

2017-11-21

Recent evidence suggests that the metastatic spread of head and neck squamous cell carcinomas (HNSCC) requires the function of cancer stem cells endowed with multipotency, self-renewal, and high tumorigenic potential. We demonstrated that cancer stem cells reside in perivascular niches and are characterized by high aldehyde dehydrogenase (ALDH) activity and high CD44 expression (ALDH high CD44 high ) in HNSCC. Here, we hypothesize that endothelial cell-secreted interleukin-6 (IL-6) contributes to tumor progression by enhancing the migratory phenotype and survival of cancer stem cells. Analysis of tissue microarrays generated from the invasive fronts of 77 HNSCC patients followed-up for up to 11 years revealed that high expression of IL-6 receptor (IL-6R) (p=0.0217) or co-receptor gp130 (p=0.0422) correlates with low HNSCC patient survival. We observed that endothelial cell-secreted factors induce epithelial to mesenchymal transition (EMT) and enhance invasive capacity of HNSCC cancer stem cells. Conditioned medium from CRISPR/Cas9-mediated IL-6 knockout primary human endothelial cells is less chemotactic for cancer stem cells in a microfluidics-based system than medium from control endothelial cells (p<0.05). Blockade of the IL-6 pathway with a humanized anti-IL-6R antibody (tocilizumab) inhibited endothelial cell-induced motility in vitro and decreased the fraction of cancer stem cells in vivo . Notably, xenograft HNSCC tumors vascularized with IL-6-knockout endothelial cells exhibited slower tumor growth and smaller cancer stem cell fraction. These findings demonstrate that endothelial cell-secreted IL-6 enhances the motility and survival of highly tumorigenic cancer stem cells, suggesting that endothelial cells can create a chemotactic gradient that enables the movement of carcinoma cells towards blood vessels.

Planarian shows decision-making behavior in response to multiple stimuli by integrative brain function.

PubMed

Inoue, Takeshi; Hoshino, Hajime; Yamashita, Taiga; Shimoyama, Seira; Agata, Kiyokazu

2015-01-01

Planarians belong to an evolutionarily early group of organisms that possess a central nervous system including a well-organized brain with a simple architecture but many types of neurons. Planarians display a number of behaviors, such as phototaxis and thermotaxis, in response to external stimuli, and it has been shown that various molecules and neural pathways in the brain are involved in controlling these behaviors. However, due to the lack of combinatorial assay methods, it remains obscure whether planarians possess higher brain functions, including integration in the brain, in which multiple signals coming from outside are coordinated and used in determining behavioral strategies. In the present study, we designed chemotaxis and thigmotaxis/kinesis tracking assays to measure several planarian behaviors in addition to those measured by phototaxis and thermotaxis assays previously established by our group, and used these tests to analyze planarian chemotactic and thigmotactic/kinetic behaviors. We found that headless planarian body fragments and planarians that had specifically lost neural activity following regeneration-dependent conditional gene knockdown (Readyknock) of synaptotagmin in the brain lost both chemotactic and thigmotactic behaviors, suggesting that neural activity in the brain is required for the planarian's chemotactic and thigmotactic behaviors. Furthermore, we compared the strength of phototaxis, chemotaxis, thigmotaxis/kinesis, and thermotaxis by presenting simultaneous binary stimuli to planarians. We found that planarians showed a clear order of predominance of these behaviors. For example, when planarians were simultaneously exposed to 400 lux of light and a chemoattractant, they showed chemoattractive behavior irrespective of the direction of the light source, although exposure to light of this intensity alone induces evasive behavior away from the light source. In contrast, when the light intensity was increased to 800 or 1600 lux and the same dose of chemoattractant was presented, planarian behaviors were gradually shifted to negative phototaxis rather than chemoattraction. These results suggest that planarians may be capable of selecting behavioral strategies via the integration of discrete brain functions when exposed to multiple stimuli. The planarian brain processes external signals received through the respective sensory neurons, thereby resulting in the production of appropriate behaviors. In addition, planarians can adjust behavioral features in response to stimulus conditions by integrating multiple external signals in the brain.

Activation of the complement system in patients with porphyrias after irradiation in vivo.

PubMed Central

Lim, H W; Poh-Fitzpatrick, M B; Gigli, I

1984-01-01

Irradiation of the forearms of two patients with erythropoietic protoporphyria and one patient with porphyria cutanea tarda resulted in an in vivo activation of the complement system, as assessed by diminution of the hemolytic titers of the third component of complement by 23-57%, and of the fifth component of complement (C5) by 19-47%. Such treatment also generated chemotactic activity for human polymorphonuclear cells; the chemotactic activity was stable at 56 degrees C and antigenically related to human C5. On Sephadex G-75 chromatography the chemotactic activity eluted with an apparent molecular weight of 15,000. These in vivo results extend our previous in vitro observation of photoactivation of complement in sera from patients with erythropoietic protoporphyria and porphyria cutanea tarda, and suggest that the complement system may participate in the pathogenesis of cutaneous phototoxicity in these patients. PMID:6392339

Fluorescent staining for leukocyte chemotaxis. Eosinophil-specific fluorescence with aniline blue.

PubMed

McCrone, E L; Lucey, D R; Weller, P F

1988-11-10

To overcome problems associated with the quantitation of human eosinophil chemotaxis in micropore filters, we have developed a fluorescent method of specifically staining eosinophils in chemotactic filters. A neutral solution of aniline blue yielded bright green fluorescent staining of the cytoplasmic granules of eosinophils. Other leukocytes and contaminating neutrophils potentially present with eosinophils did not fluoresce with aniline blue. The fluorescent staining eosinophils within filters provided bright, non-fading images that facilitated visual microscopic counting and were of sufficiently high contrast, unlike those with conventional eosinophil stains, to allow image analyzer based enumeration of eosinophil chemotactic responses at levels through the filters. Although not cell type-specific, congo red and ethidium bromide also provided high contrast, fluorescent images of all leukocyte types within chemotactic filters. Fluorescent staining with aniline blue constitutes a rapid, stable and eosinophil-specific stain that facilitates the visual or image analyzer-based quantitation of eosinophil chemotaxis.

Attachment, invasion, chemotaxis, and proteinase expression of B16-BL6 melanoma cells exhibiting a low metastatic phenotype after exposure to dietary restriction of tyrosine and phenylalanine.

PubMed

Uhlenkott, C E; Huijzer, J C; Cardeiro, D J; Elstad, C A; Meadows, G G

1996-03-01

We previously reported that low levels of tyrosine (Tyr) and phenylalanine (Phe) alter the metastatic phenotype of B16-BL6 (BL6) murine melanoma and select for tumor cell populations with decreased lung colonizing ability. To more specifically characterize the effects of Tyr and Phe restriction on the malignant phenotype of BL6, we investigated in vitro attachment, invasion, proteinase expression, and chemotaxis of high and low metastatic BL6 variants. High metastatic variant cells were isolated from subcutaneous tumors of mice fed a nutritionally complete diet (ND cells) and low metastatic variant cells were isolated from mice fed a diet restricted in Tyr and Phe (LTP cells). Results indicate that attachment to reconstituted basement membrane (Matrigel) was significantly reduced in LTP cells as compared to ND cells. Attachment to collagen IV, laminin, and fibronectin were similar between the two variants. Invasion through Matrigel and growth factor-reduced Matrigel were significantly decreased in LTP cells as compared to ND cells. Zymography revealed the presence of M(r) 92,000 and M(r) 72,000 progelatinases, tissue plasminogen activator, and urokinase plasminogen activator in the conditioned medium of both variants; however, there were no differences in activity of these secreted proteinases between the two variants. Growth of the variants on growth factor-reduced Matrigel similarly induced expression of the M(r) 92,000 progelatinase. The variants exhibited similar chemotactic responses toward laminin. However, the chemotactic response toward fibronectin by LTP cells was significantly increased. MFR5, a monoclonal antibody which selectively blocks function of the alpha 5 chain of the alpha 5 beta 1 integrin, VLA-5, decreased the chemotactic response toward fibronectin of ND cells by 37%; the chemotactic response by LTP cells was reduced by 49%. This effect was specific for fibronectin-mediated chemotaxis since the chemotaxis toward laminin and invasion through Matrigel were not altered by the presence of MFR5. The surface expression of VLA-5 was significantly increased in LTP cells as compared to ND cells by flow cytometric analysis. These observations suggest that limitation of Tyr and Phe either directly modifies BL6 or selects for subpopulations with altered in vitro invasion, chemotaxis, and integrin expression.

Pore-formation by adenylate cyclase toxoid activates dendritic cells to prime CD8+ and CD4+ T cells.

PubMed

Svedova, Martina; Masin, Jiri; Fiser, Radovan; Cerny, Ondrej; Tomala, Jakub; Freudenberg, Marina; Tuckova, Ludmila; Kovar, Marek; Dadaglio, Gilles; Adkins, Irena; Sebo, Peter

2016-04-01

The adenylate cyclase toxin-hemolysin (CyaA) of Bordetella pertussis is a bi-functional leukotoxin. It penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into their cytosol its N-terminal adenylate cyclase enzyme domain (~400 residues). In parallel, ~1300 residue-long RTX hemolysin moiety of CyaA forms cation-selective pores and permeabilizes target cell membrane for efflux of cytosolic potassium ions. The non-enzymatic CyaA-AC(-) toxoid, has repeatedly been successfully exploited as an antigen delivery tool for stimulation of adaptive T-cell immune responses. We show that the pore-forming activity confers on the CyaA-AC(-) toxoid a capacity to trigger Toll-like receptor and inflammasome signaling-independent maturation of CD11b-expressing dendritic cells (DC). The DC maturation-inducing potency of mutant toxoid variants in vitro reflected their specifically enhanced or reduced pore-forming activity and K(+) efflux. The toxoid-induced in vitro phenotypic maturation of DC involved the activity of mitogen activated protein kinases p38 and JNK and comprised increased expression of maturation markers, interleukin 6, chemokines KC and LIX and granulocyte-colony-stimulating factor secretion, prostaglandin E2 production and enhancement of chemotactic migration of DC. Moreover, i.v. injected toxoids induced maturation of splenic DC in function of their cell-permeabilizing capacity. Similarly, the capacity of DC to stimulate CD8(+) and CD4(+) T-cell responses in vitro and in vivo was dependent on the pore-forming activity of CyaA-AC(-). This reveals a novel self-adjuvanting capacity of the CyaA-AC(-) toxoid that is currently under clinical evaluation as a tool for delivery of immunotherapeutic anti-cancer CD8(+) T-cell vaccines into DC.

Bacterial chemoreceptors: high-performance signaling in networked arrays.

PubMed

Hazelbauer, Gerald L; Falke, Joseph J; Parkinson, John S

2008-01-01

Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation. The mechanisms that mediate these high-performance functions involve not only actions of individual proteins but also interactions among clusters of components, localized in extensive patches of thousands of molecules. Recently, these patches have been imaged in native cells, important features of chemoreceptor structure and on-off switching have been identified, and new insights have been gained into the structural basis and functional consequences of higher order interactions among sensory components. These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device.

Bacterial chemoreceptors: high-performance signaling in networked arrays

PubMed Central

Hazelbauer, Gerald L.; Falke, Joseph J.; Parkinson, John S.

2010-01-01

Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation. The mechanisms that mediate these high-performance functions involve not only actions of individual proteins but also interactions among clusters of components, localized in extensive patches of thousands of molecules. Recently, these patches have been imaged in native cells, important features of chemoreceptor structure and on–off switching have been identified, and new insights have been gained into the structural basis and functional consequences of higher order interactions among sensory components. These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device. PMID:18165013

Comparison of neutrophil functions between two strains of inbred mice.

PubMed

Zhang, Xiaohuan; Zhao, Sainan; Sun, Luping; Li, Wenqing; Glogauer, Michael; Hu, Yan

2016-12-01

In this study, differences between two strains of inbred mice in aspects of neutrophil function, namely Rac1 expression, chemotaxis, nicotinamide adenine dinucleotide phosphate oxidase activity and formation of neutrophil extracellular traps (NETs), were determined. Neutrophils from CBA/CaH mice exhibited weaker Rac1 expression and a slower chemotactic gradient than BALB/c mice. Furthermore, PMA- or fMLP-stimulated neutrophils from CBA/CaH mice generated much less superoxide and NETs than similarly stimulated neutrophils from BALB/c mice. These findings suggest that neutrophils from BALB/c mice are functionally more efficient than those from CBA/CaH mice. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Caffeine, dibutyryl cyclic-AMP and heparin affect the chemotactic and phagocytotic activities of neutrophils for boar sperm in vitro.

PubMed

Li, J-C; Yamaguchi, S; Kondo, Y; Funahashi, H

2011-04-15

The objective was to examine the effects of caffeine, dibutyryl cyclic AMP, and heparin on the chemotaxis and/or phagocytosis of PMNs for porcine sperm. The chemotactic activity of PMNs, determined in a blind well chamber, increased (P < 0.05) when fresh serum was added to the medium (control containing BSA, 1109.5 cells/mm(2) vs serum, 1226.3 cells/mm(2)), regardless of the presence of sperm (control, 1121.1 cells/mm(2) vs serum, 1245.8 cells/mm(2)), whereas heat-inactivated serum did not affect activity (without sperm, 1099.4 cells/mm(2) and with sperm, 1132.6 cells/mm(2)). Regardless of live and dead sperm and of the origin of PMNs (boars vs sows), the phagocytotic activity of PMNs, as determined by co-culture of PMNs with sperm for 60 min, increased (P < 0.05) in the presence of fresh serum containing active complement (46.7 and 43.0%, respectively), but stimulation was decreased (P < 0.05) when 1 mM or higher concentrations of caffeine was added to the medium (from 40.7 to 20.8-31.6%). The origin of PMNs (sows vs boars) did not significantly affect phagocytotic activity. The percentage of PMNs that phagocytized polystyrene latex beads decreased when 2 mM caffeine was added to the medium containing porcine serum (from 43.7 to 21.5%). Serum-stimulated chemotactic activity of PMNs (1089.9 cells/mm(2)) was also reduced (P < 0.05) with 2 mM caffeine (942.5 cells/mm(2)). Furthermore, dibutyryl cAMP at ≥ 0.1 mM or heparin at ≥ 100 μg/mL decreased phagocytotic activity, in a concentration-dependent manner (P < 0.05). Supplementation of PMNs with heparin at 100 or 500 μg/mL decreased (P < 0.05) chemotactic activity in the presence of serum (from 1137.1 cells/mm(2) to 1008.8-1026.3 cells/mm(2)). We inferred that opsonization in the presence of active complement stimulated phagocytotic and chemotactic activities of PMNs, whereas supplementation with caffeine and dibutyryl cAMP (which could be associated with the intracellular cAMP level of PMNs) or adding heparin decreased serum-stimulated phagocytotic and chemotactic activities. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Role of Progesterone Receptor Isoforms in Regulation of Cell Adhesion and Apoptosis

DTIC Science & Technology

2002-06-01

repeatable) (figure 1 below). We used taxol to induce apoptosis instead of tumor necrosis factor (TNF) (as initially proposed in the grant) because...highlighted in red in Fig. 6A), monocyte chemotactic protein (MCP; open arrow in Fig. 6A and isolated in Fig. 6B, top) and bullous pemphigoid antigen...red. The open arrow indicates monocyte chemotactic protein (MCP) and closed arrow indi- cates bullous pemphigoid antigen (BPAG). B, top, isolated

Disruption of Chemoreceptor Signaling Arrays by High Levels of CheW, the Receptor-Kinase Coupling Protein

PubMed Central

Cardozo, Marcos J.; Massazza, Diego A.; Parkinson, John S.; Studdert, Claudia A.

2017-01-01

Summary During chemotactic signaling by Escherichia coli, the small cytoplasmic CheW protein couples the histidine kinase CheA to chemoreceptor control. Although essential for assembly and operation of receptor signaling complexes, CheW in stoichiometric excess disrupts chemotactic behavior. To explore the mechanism of the CheW excess effect, we measured the physiological consequences of high cellular levels of wild-type CheW and of several CheW variants with reduced or enhanced binding affinities for receptor molecules. We found that high levels of CheW interfered with trimer assembly, prevented CheA activation, blocked cluster formation, disrupted chemotactic ability, and elevated receptor methylation levels. The severity of these effects paralleled the receptor binding affinities of the CheW variants. Because trimer formation may be an obligate step in the assembly of ternary signaling complexes and higher-order receptor arrays, we suggest that all CheW excess effects stem from disruption of trimer assembly. We propose that the CheW-binding sites in receptor dimers overlap their trimer contact sites and that high levels of CheW saturate the receptor binding sites, preventing trimer assembly. The CheW-trapped receptor dimers seem to be improved substrates for methyltransferase reactions, but cannot activate CheA or assemble into clusters, processes that are essential for chemotactic signaling. PMID:20487303

Quantitative analysis of transverse bacterial migration induced by chemotaxis in a packed column with structured physical heterogeneity.

PubMed

Wang, Meng; Ford, Roseanne M

2010-01-15

A two-dimensional mathematical model was developed to simulate transport phenomena of chemotactic bacteria in a sand-packed column designed with structured physical heterogeneity in the presence of a localized chemical source. In contrast to mathematical models in previous research work, in which bacteria were typically treated as immobile colloids, this model incorporated a convective-like chemotaxis term to represent chemotactic migration. Consistency between experimental observation and model prediction supported the assertions that (1) dispersion-induced microbial transfer between adjacent conductive zones occurred at the interface and had little influence on bacterial transport in the bulk flow of the permeable layers and (2) the enhanced transverse bacterial migration in chemotactic experiments relative to nonchemotactic controls was mainly due to directed migration toward the chemical source zone. On the basis of parameter sensitivity analysis, chemotactic parameters determined in bulk aqueous fluid were adequate to predict the microbial transport in our intermediate-scale porous media system. Additionally, the analysis of adsorption coefficient values supported the observation of a previous study that microbial deposition to the surface of porous media might be decreased under the effect of chemoattractant gradients. By quantitatively describing bacterial transport and distribution in a heterogeneous system, this mathematical model serves to advance our understanding of chemotaxis and motility effects in granular media systems and provides insights for modeling microbial transport in in situ microbial processes.

Plant-Adapted Escherichia coli Show Increased Lettuce Colonizing Ability, Resistance to Oxidative Stress and Chemotactic Response

PubMed Central

Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

2014-01-01

Background Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. Methods/Principal Findings This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. Conclusion/Significance These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues. PMID:25313845

Azospirillum brasilense Chemotaxis Depends on Two Signaling Pathways Regulating Distinct Motility Parameters

PubMed Central

Mukherjee, Tanmoy; Kumar, Dhivya; Burriss, Nathan; Xie, Zhihong

2016-01-01

ABSTRACT The genomes of most motile bacteria encode two or more chemotaxis (Che) systems, but their functions have been characterized in only a few model systems. Azospirillum brasilense is a motile soil alphaproteobacterium able to colonize the rhizosphere of cereals. In response to an attractant, motile A. brasilense cells transiently increase swimming speed and suppress reversals. The Che1 chemotaxis pathway was previously shown to regulate changes in the swimming speed, but it has a minor role in chemotaxis and root surface colonization. Here, we show that a second chemotaxis system, named Che4, regulates the probability of swimming reversals and is the major signaling pathway for chemotaxis and wheat root surface colonization. Experimental evidence indicates that Che1 and Che4 are functionally linked to coordinate changes in the swimming motility pattern in response to attractants. The effect of Che1 on swimming speed is shown to enhance the aerotactic response of A. brasilense in gradients, likely providing the cells with a competitive advantage in the rhizosphere. Together, the results illustrate a novel mechanism by which motile bacteria utilize two chemotaxis pathways regulating distinct motility parameters to alter movement in gradients and enhance the chemotactic advantage. IMPORTANCE Chemotaxis provides motile bacteria with a competitive advantage in the colonization of diverse niches and is a function enriched in rhizosphere bacterial communities, with most species possessing at least two chemotaxis systems. Here, we identify the mechanism by which cells may derive a significant chemotactic advantage using two chemotaxis pathways that ultimately regulate distinct motility parameters. PMID:27068592

Azospirillum brasilense Chemotaxis Depends on Two Signaling Pathways Regulating Distinct Motility Parameters.

PubMed

Mukherjee, Tanmoy; Kumar, Dhivya; Burriss, Nathan; Xie, Zhihong; Alexandre, Gladys

2016-06-15

The genomes of most motile bacteria encode two or more chemotaxis (Che) systems, but their functions have been characterized in only a few model systems. Azospirillum brasilense is a motile soil alphaproteobacterium able to colonize the rhizosphere of cereals. In response to an attractant, motile A. brasilense cells transiently increase swimming speed and suppress reversals. The Che1 chemotaxis pathway was previously shown to regulate changes in the swimming speed, but it has a minor role in chemotaxis and root surface colonization. Here, we show that a second chemotaxis system, named Che4, regulates the probability of swimming reversals and is the major signaling pathway for chemotaxis and wheat root surface colonization. Experimental evidence indicates that Che1 and Che4 are functionally linked to coordinate changes in the swimming motility pattern in response to attractants. The effect of Che1 on swimming speed is shown to enhance the aerotactic response of A. brasilense in gradients, likely providing the cells with a competitive advantage in the rhizosphere. Together, the results illustrate a novel mechanism by which motile bacteria utilize two chemotaxis pathways regulating distinct motility parameters to alter movement in gradients and enhance the chemotactic advantage. Chemotaxis provides motile bacteria with a competitive advantage in the colonization of diverse niches and is a function enriched in rhizosphere bacterial communities, with most species possessing at least two chemotaxis systems. Here, we identify the mechanism by which cells may derive a significant chemotactic advantage using two chemotaxis pathways that ultimately regulate distinct motility parameters. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A novel neutrophil-activating factor released by Trichomonas vaginalis.

PubMed Central

Shaio, M F; Lin, P R; Lee, C S; Hou, S C; Tang, P; Yang, K D

1992-01-01

We have investigated the effects of a novel neutrophil-activating factor released by Trichomonas vaginalis (TV-NAF) on neutrophil chemotaxis. TV-NAF was present in the supernatant from 10(7) T. vaginalis (STV) cultured in 1 ml of serum-free Hanks' balanced salt solution (HBSS) at 37 degrees C for 30 min. With a multichamber chemotactic assay, we found that there were 112 +/- 15 migrated neutrophils (mean +/- standard deviation, n = 7) for STV and 11 +/- 4 for HBSS per high-power field (x 400). STV was also able to induce neutrophil actin assembly (increased 1.5-fold), enhance expression of complement receptor type 3 (increased 5-fold), and promote intracellular calcium mobilization (increased 2.5-fold). There was no chemotactic activity in the preparation of STV from killed trichomonads. The fact that heating up to 100 degrees C or deproteinization by treatment with proteinase K at 65 degrees C for 1 h did not abolish its chemotactic activity suggests that the TV-NAF involved was not a protein. The chemotactic activity of TV-NAF was associated with the fraction containing small molecules of less than 3,000 Da. Therefore, the possibility that eicosanoid production by trichomonads is responsible for neutrophil activation was investigated. Leukotriene B4 (LTB4; 500 pg/ml) but not thromboxane B2 (< 20 pg/ml) or prostaglandin E2 (< 8 pg/ml) was found in the STV by radioimmunoassay. Production of LTB4 by trichomonads was time dependent and increased twofold when arachidonic acid (100 microM) was added but was not decreased when eicosanoid inhibitors were present. Evidence for the presence of LTB4 in STV was further provided by the fact that rabbit anti-LTB4 antiserum could abolish the chemotactic activity of STV. These studies suggest that the spontaneous release of TV-NAF, which is most likely LTB4, may activate neutrophils, presumably through a different arachidonate metabolic pathway than that in mammalian cells. PMID:1398962

Optimal methylation noise for best chemotactic performance of E. coli

NASA Astrophysics Data System (ADS)

Dev, Subrata; Chatterjee, Sakuntala

2018-03-01

In response to a concentration gradient of chemoattractant, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high chemoattractant concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequences on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell in a significant way. We model the intracellular reaction network in terms of coupled time evolution of three stochastic variables—kinase activity, methylation level, and CheY-P protein level—and study the effect of methylation noise on the chemotactic performance of the cell. In presence of a spatially varying nutrient concentration profile, a good chemotactic performance allows the cell to climb up the concentration gradient quickly and localize in the nutrient-rich regions in the long time limit. Our simulations show that the best performance is obtained at an optimal noise strength. While it is expected that chemotaxis will be weaker for very large noise, it is counterintuitive that the performance worsens even when noise level falls below a certain value. We explain this striking result by detailed analysis of CheY-P protein level statistics for different noise strengths. We show that when the CheY-P level falls below a certain (noise-dependent) threshold the cell tends to move down the concentration gradient of the nutrient, which has a detrimental effect on its chemotactic response. This threshold value decreases as noise is increased, and this effect is responsible for noise-induced enhancement of chemotactic performance. In a harsh chemical environment, when the nutrient degrades with time, the amount of nutrient intercepted by the cell trajectory is an effective performance criterion. In this case also, depending on the nutrient lifetime, we find an optimum noise strength when the performance is at its best.

Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity.

PubMed

Nagasawa, Hideko; Uto, Yoshihiro; Sasaki, Hideyuki; Okamura, Natsuko; Murakami, Aya; Kubo, Shinichi; Kirk, Kenneth L; Hori, Hitoshi

2005-01-01

The Gc protein (human group-specific component (Gc), a vitamin D-binding protein or Gc globulin), has important physiological functions that include involvement in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5a for neutrophils in inflammation and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In this review, the structure and function of the Gc protein is focused on especially with regard to Gc genotyping and GcMAF precursor activity. A discussion of the research strategy "GcMAF as a target for drug discovery" is included, based on our own research.

Vascular Endothelial Growth Factor (VEGF) Promotes Assembly of the p130Cas Interactome to Drive Endothelial Chemotactic Signaling and Angiogenesis.

PubMed

Evans, Ian M; Kennedy, Susan A; Paliashvili, Ketevan; Santra, Tapesh; Yamaji, Maiko; Lovering, Ruth C; Britton, Gary; Frankel, Paul; Kolch, Walter; Zachary, Ian C

2017-02-01

p130Cas is a polyvalent adapter protein essential for cardiovascular development, and with a key role in cell movement. In order to identify the pathways by which p130Cas exerts its biological functions in endothelial cells we mapped the p130Cas interactome and its dynamic changes in response to VEGF using high-resolution mass spectrometry and reconstruction of protein interaction (PPI) networks with the aid of multiple PPI databases. VEGF enriched the p130Cas interactome in proteins involved in actin cytoskeletal dynamics and cell movement, including actin-binding proteins, small GTPases and regulators or binders of GTPases. Detailed studies showed that p130Cas association of the GTPase-binding scaffold protein, IQGAP1, plays a key role in VEGF chemotactic signaling, endothelial polarization, VEGF-induced cell migration, and endothelial tube formation. These findings indicate a cardinal role for assembly of the p130Cas interactome in mediating the cell migratory response to VEGF in angiogenesis, and provide a basis for further studies of p130Cas in cell movement. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies.

PubMed Central

Keogan, M T; Esnault, V L; Green, A J; Lockwood, C M; Brown, D L

1992-01-01

Anti-neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminol-amplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti-double stranded DNA positive sera (P < 0.01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminescence system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f-Met-Leu-Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan-activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis. PMID:1424279

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes glioblastoma cell chemotaxis via Lyn activation

PubMed Central

Tran, Nhan L.

2014-01-01

The long-term survival of patients with glioblastoma is compromised by the proclivity for local invasion into the surrounding normal brain, escaping surgical resection and contributing to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell invasion via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the Rho guanosine triphosphatase family member Rac1. Here, we demonstrate that TWEAK acts as a chemotactic factor for glioma cells, a potential process for driving cell invasion into the surrounding brain tissue. TWEAK exposure induced the activation of Src family kinases (SFKs), and pharmacologic suppression of SFK activity inhibited TWEAK-induced chemotactic migration. We employed a multiplexed Luminex assay and identified Lyn as a candidate SFK activated by TWEAK. Depletion of Lyn suppressed TWEAK-induced chemotaxis and Rac1 activity. Furthermore, Lyn gene expression levels increase with primary glioma tumor grade and inversely correlate with patient survival. These results show that TWEAK-induced glioma cell chemotaxis is dependent upon Lyn kinase function and, thus, provides opportunities for therapeutic targeting of this deadly disease. PMID:23975833

Chemotaxis of C. elegans in 3D media: a model for navigation of undulatory microswimmers

NASA Astrophysics Data System (ADS)

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

2017-11-01

While the natural environment of C. elegans consists of complex 3D media (e.g., decomposing organic matter and water), most studies of chemotactic behavior of this nematode are limited to 2D. We present a 3D chemotaxis model that combines a realistic geometrical representation of body movements associated with 3D maneuvers, an analysis of mechanical interactions of the nematode body with the surrounding medium to determine nematode trajectories, and a simple memory-function description of chemosensory apparatus that controls the frequency, magnitude, and timing of turning maneuvers. We show that two main chemotaxis strategies of C. elegans moving in 2D, i.e., the biased random walk and gradual turn, are effective also in 3D, provided that 2D turns are supplemented by the roll maneuvers that enable 3D reorientation. Optimal choices of chemosensing and gait-control parameters are discussed; we show that the nematode can maintain efficient chemotaxis in burrowing and swimming by adjusting the undulation frequency alone, without changing the chemotactic component of the body control. Understanding how C. elegans efficiently navigates in 3D media may help in developing self-navigating artificial microswimmers. Supported by NSF Grant No. CBET 1603627.

Saddle-node bifurcation to jammed state for quasi-one-dimensional counter-chemotactic flow.

PubMed

Fujii, Masashi; Awazu, Akinori; Nishimori, Hiraku

2010-07-01

The transition of a counter-chemotactic particle flow from a free-flow state to a jammed state in a quasi-one-dimensional path is investigated. One of the characteristic features of such a flow is that the constituent particles spontaneously form a cluster that blocks the path, called a path-blocking cluster (PBC), and causes a jammed state when the particle density is greater than a threshold value. Near the threshold value, the PBC occasionally collapses on itself to recover the free flow. In other words, the time evolution of the size of the PBC governs the flux of a counter-chemotactic flow. In this Rapid Communication, on the basis of numerical results of a stochastic cellular automata (SCA) model, we introduce a Langevin equation model for the size evolution of the PBC that reproduces the qualitative characteristics of the SCA model. The results suggest that the emergence of the jammed state in a quasi-one-dimensional counterflow is caused by a saddle-node bifurcation.

Osmotaxis in Escherichia coli through changes in motor speed

PubMed Central

Rosko, Jerko; Martinez, Vincent A.; Poon, Wilson C. K.

2017-01-01

Bacterial motility, and in particular repulsion or attraction toward specific chemicals, has been a subject of investigation for over 100 years, resulting in detailed understanding of bacterial chemotaxis and the corresponding sensory network in many bacterial species. For Escherichia coli most of the current understanding comes from the experiments with low levels of chemotactically active ligands. However, chemotactically inactive chemical species at concentrations found in the human gastrointestinal tract produce significant changes in E. coli’s osmotic pressure and have been shown to lead to taxis. To understand how these nonspecific physical signals influence motility, we look at the response of individual bacterial flagellar motors under stepwise changes in external osmolarity. We combine these measurements with a population swimming assay under the same conditions. Unlike for chemotactic response, a long-term increase in swimming/motor speeds is observed, and in the motor rotational bias, both of which scale with the osmotic shock magnitude. We discuss how the speed changes we observe can lead to steady-state bacterial accumulation. PMID:28874571

CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas.

PubMed

Deininger, M H; Zhao, Y; Schluesener, H J

1999-01-01

CP-10 (chemotactic protein of m.w. 10,000) is a member of the S100 superfamily of Ca2+ binding peptides, which has potent chemotactic activity for murine and human myeloid cells. Here we report on the generation of monoclonal antibodies against CP-10 and accumulation of CP-10+ cells during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), uveitis (EAU) and in experimentally transplanted C6 gliomas. During acute inflammation, CP-10 is mainly expressed by large ED1+ monocytic perivascular cells that accumulate at days 11-14. CP-10+ cells are predominantly located in areas of cellular infiltration but are as well found in the meninges and infiltrating the brain parenchyma. In transplanted gliomas, CP-10+ cells are located exclusively within the tumor parenchyma. Using double labeling experiments, other cells participating in the inflammatory reaction were found to express CP-10, like few lymphoblastic W3/13+ cells in the vicinity of the inflammatory infiltrate.

Physical mechanisms for chemotactic pattern formation by bacteria.

PubMed Central

Brenner, M P; Levitov, L S; Budrene, E O

1998-01-01

This paper formulates a theory for chemotactic pattern formation by the bacteria Escherichia coli in the presence of excreted attractant. In a chemotactically neutral background, through chemoattractant signaling, the bacteria organize into swarm rings and aggregates. The analysis invokes only those physical processes that are both justifiable by known biochemistry and necessary and sufficient for swarm ring migration and aggregate formation. Swarm rings migrate in the absence of an external chemoattractant gradient. The ring motion is caused by the depletion of a substrate that is necessary to produce attractant. Several scaling laws are proposed and are demonstrated to be consistent with experimental data. Aggregate formation corresponds to finite time singularities in which the bacterial density diverges at a point. Instabilities of swarm rings leading to aggregate formation occur via a mechanism similar to aggregate formation itself: when the mass density of the swarm ring exceeds a threshold, the ring collapses cylindrically and then destabilizes into aggregates. This sequence of events is demonstrated both in the theoretical model and in the experiments. PMID:9545032

Simple Microfluidic Device For Studying Chemotaxis In Response To Dual Gradients

PubMed Central

Moussavi-Haramic, S. F.; Pezzi, H. M.; Huttenlocher, A.; Beebe, D. J.

2016-01-01

Chemotaxis is a fundamental biological process where complex chemotactic gradients are integrated and prioritized to guide cell migration toward specific locations. To understand the mechanisms of gradient dependent cell migration, it is important to develop in vitro models that recapitulate key attributes of the chemotactic cues present in vivo. Current in vitro tools for studying cell migration are not amenable to easily study the response of neutrophils to dual gradients. Many of these systems require external pumps and complex setups to establish and maintain the gradients. Here we report a simple yet innovative microfluidic device for studying cell migration in the presence of dual chemotactic gradients through a 3-dimensional substrate. The device is tested and validated by studying the migration of the neutrophil-like cell line PLB-985 to gradients of fMLP. Furthermore, the device is expanded and used with heparinised whole blood, whereupon neutrophils were observed to migrate from whole blood towards gradients of fMLP eliminating the need for any neutrophil purification or capture steps. PMID:25893484

The Vi Capsular Polysaccharide Enables Salmonella enterica Serovar Typhi to Evade Microbe-Guided Neutrophil Chemotaxis

PubMed Central

Wangdi, Tamding; Lee, Cheng-Yuk; Spees, Alanna M.; Yu, Chenzhou; Kingsbury, Dawn D.; Winter, Sebastian E.; Hastey, Christine J.; Wilson, R. Paul

2014-01-01

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. PMID:25101794

The HIV-1 gp41 ectodomain is cleaved by matriptase to produce a chemotactic peptide that acts through FPR2

PubMed Central

Wood, Matthew P; Cole, Amy L; Eade, Colleen R; Chen, Li-Mei; Chai, Karl X; Cole, Alexander M

2014-01-01

Several aspects of HIV-1 virulence and pathogenesis are mediated by the envelope protein gp41. Additionally, peptides derived from the gp41 ectodomain have been shown to induce chemotaxis in monocytes and neutrophils. Whereas this chemotactic activity has been reported, it is not known how these peptides could be produced under biological conditions. The heptad repeat 1 (HR1) region of gp41 is exposed to the extracellular environment and could therefore be susceptible to proteolytic processing into smaller peptides. Matriptase is a serine protease expressed at the surface of most epithelia, including the prostate and mucosal surfaces. Here, we present evidence that matriptase efficiently cleaves the HR1 portion of gp41 into a 22-residue chemotactic peptide MAT-1, the sequence of which is highly conserved across HIV-1 clades. We found that MAT-1 induced migration of primary neutrophils and monocytes, the latter of which act as a cellular reservoir of HIV during early stage infection. We then used formyl peptide receptor 1 (FPR1) and FPR2 inhibitors, along with HEK 293 cells, to demonstrate that MAT-1 can induce chemotaxis specifically using FPR2, a receptor found on the surface of monocytes, macrophages and neutrophils. These findings are the first to identify a proteolytic cleavage product of gp41 with chemotactic activity and highlight a potential role for matriptase in HIV-1 transmission and infection at epithelial surfaces and within tissue reservoirs of HIV-1. PMID:24617769

Coupled effects of chemotaxis and growth on traveling bacterial waves.

PubMed

Yan, Zhifeng; Bouwer, Edward J; Hilpert, Markus

2014-08-01

Traveling bacterial waves are capable of improving contaminant remediation in the subsurface. It is fairly well understood how bacterial chemotaxis and growth separately affect the formation and propagation of such waves. However, their interaction is not well understood. We therefore perform a modeling study to investigate the coupled effects of chemotaxis and growth on bacterial migration, and examine their effects on contaminant remediation. We study the waves by using different initial electron acceptor concentrations for different bacteria and substrate systems. Three types of traveling waves can occur: a chemotactic wave due to the biased movement of chemotactic bacteria resulting from metabolism-generated substrate concentration gradients; a growth/decay/motility wave due to a dynamic equilibrium between bacterial growth, decay and random motility; and an integrated wave due to the interaction between bacterial chemotaxis and growth. Chemotaxis hardly enhances the bacterial propagation if it is too weak to form a chemotactic wave or its wave speed is less than half of the growth/decay/motility wave speed. However, chemotaxis significantly accelerates bacterial propagation once its wave speed exceeds the growth/decay/motility wave speed. When convection occurs, it speeds up the growth/decay/motility wave but slows down or even eliminates the chemotactic wave due to the dispersion. Bacterial survival proves particularly important for bacterial propagation. Therefore we develop a conceptual model to estimate the speed of growth/decay/motility waves. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of tilmicosin on chemotactic, phagocytic, and bactericidal activities of bovine and porcine alveolar macrophages.

PubMed

Brumbaugh, Gordon W; Herman, James D; Clancy, Julianne S; Burden, Kyland I; Barry, Tracie; Simpson, R B; López, Hector Sumano

2002-01-01

To evaluate chemotactic, phagocytic, and bactericidal activities of bovine and porcine alveolar macrophages (AM) exposed to tilmicosin. 12 healthy calves and 12 healthy pigs. Lungs were obtained immediately after euthanasia; AM were collected by means of bronchoalveolar lavage and density gradient centrifugation. Chemotactic activity was evaluated by exposing AM to lipopolysaccharide or macrophage inhibitory peptide during incubation with tilmicosin. Phagocytic activity was evaluated by incubating AM with tilmicosin for 24 hours and then with tilmicosin-resistant Salmonella serotype Typhimurium. Bactericidal activity was evaluated by incubating AM with tilmicosin (0, 10, or 20 microg/ml for bovine AM; 0 or 10 microg/ml or 10 microg/ml but washed free of tilmicosin for porcine AM) and then with Mannheimia haemolytica (bovine AM) or with Actinobacillus pleuropneumoniae or Pasteurella multocida (porcine AM). Tilmicosin had no significant effects on chemotactic or phagocytic activities of bovine or porcine AM. The time-course of bactericidal activity was best described by polynomial equations. Time to cessation of bacterial growth and area under the time versus bacterial number curve were significantly affected by incubation of AM with tilmicosin. Results show that bactericidal activity of bovine and porcine AM was enhanced by tilmicosin, but not in proportion to the reported ability of AM to concentrate tilmicosin intracellularly. With or without exposure to tilmicosin, the time-course of bactericidal activity of bovine AM against M haemolytica and of porcine AM against A pleuropneumoniae or P multocida was too complex to be reduced to a simple linear equation.

Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

PubMed

Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

2017-11-01

Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD 4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD 4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 10 3 RFU; LTD 4 10 nM alone, 511 ± 39.2 × 10 3 RFU; LTD 4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 10 3 RFU). LTD 4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

Coupled effect of chemotaxis and growth on microbial distributions in organic-amended aquifer sediments: Observations from laboratory and field studies

USGS Publications Warehouse

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

2008-01-01

The inter-relationship of growth and chemotactic response exhibited by two common soil-inhabiting bacteria was investigated to determine its impact on bacterial migration. Filter-chambers were used to simulate aquifer sediments characterized by vertical gradients of organic contaminants in both artificial groundwater flow systems in the laboratory and within the screened intervals of observation wells in a sandy aquifer. A labile model contaminant (acetate) was added to the top compartments of the three-part chambers, whereas bacteria with a demonstrated propensity to grow on and chemotactically respond to acetate were introduced to the lower compartments, The motility and chemotactic response of Pseudomonas putida F1 resulted in 40 to 110% greater abundances in the upper compartments and concomitant 22 to 70% depletions in the lower compartments relative to the nonchemotactic controls over 2 days. Bacteria were in greatest abundance within the sand plug that separated the upper and lower compartments where sharp acetate gradients induced a strong chemotactic response. This observation was consistent with predictions from a mathematical model. In agreement with the laboratory results, the down-well filter-chamber incubations with Pseudomonas stutzeri in the aquifer indicated that 91% fewer bacteria resided in the lower compartment than the control experiment without acetate at 15 h. The combination of chemotaxis and growth greatly accelerated the migration of bacteria toward and subsequent abundance at the higher acetate concentration. ?? 2008 American Chemical Society.

A visual study of chemotaxis of human lymphocytes using a collagen-gel assay.

PubMed

Wilkinson, P C

1985-01-21

Time-lapse cinematography was used to study the chemotactic responsiveness of human blood lymphocytes as defined by morphological orientation and directional locomotion in gradients. At present, evidence for lymphocyte chemotaxis is indirect since neither of these essential features can be demonstrated with Boyden filter assays. Few lymphocytes direct from blood were motile, but culture in vitro for 1-3 days increased the proportion of locomotor forms to 30-40%. These cells were placed on 3-D collagen gels, and a chemotactic source was presented nearby on a small filter placed on the surface of, or within, the gel. The minority of lymphocytes that were capable of locomotion showed chemotactic responses to filters soaked in lipopolysaccharide if fresh human serum (20%), but not heat-inactivated serum, was present. Lymphocytes responded by protrusion of a lamella in the direction of the gradient source: 76% of locomotor lymphocytes showed their first orientation into the 180 degrees sector facing the source. They then moved directionally towards the source. The response to purified C5 peptides was equivocal. The locomotor lymphocytes showed a chemotactic response to supernatant fluids derived from cultures of the adherent mononuclear cell fraction from human blood (greater than 80% monocytes), judged by the same criteria. No particular lymphocyte type constituted the locomotor population. After exposure to LPS-activated serum, both T and B lymphocytes showed locomotor forms. There were slightly more T4+ cells among the locomotor population than among the population as a whole.

Cysteinyl leukotrienes promote human airway smooth muscle migration.

PubMed

Parameswaran, Krishnan; Cox, Gerard; Radford, Katherine; Janssen, Luke J; Sehmi, Roma; O'Byrne, Paul M

2002-09-01

Cysteinyl leukotrienes promote airway smooth muscle (ASM) contraction and proliferation. Little is known about their role in ASM migration. We investigated this using cultured human ASMs (between the second and fifth passages) obtained from the large airways of resected nonasthmatic lung. Platelet-derived growth factor-BB (1 ng/ml) promoted significant (3.5-fold) ASM migration of myocytes across collagen-coated 8- micro m polycarbonate membranes in Transwell culture plates. Leukotriene E(4) (10(-7), 10(-8), 10(-9) M) did not demonstrate a chemotactic effect; it did promote chemokinesis. Priming by leukotriene E(4) (10(-7) M) significantly augmented the directional migratory response to platelet-derived growth factor (1.5-fold, p < 0.05). This was blocked by montelukast (10(-6) M), demonstrating the effect to be mediated by the cysteinyl leukotriene receptor. The "priming effect" was also partially attenuated by prostaglandin E(2) (10(-7) M). Whereas both the chemokinetic and the chemotactic "primed" responses were equally attenuated by a p38 mitogen-activated protein kinase inhibitor (SB203580, 25 micro M) and by a Rho-kinase inhibitor (Y27632, 10 micro M), the chemotactic response showed greater inhibition than chemokinesis by a phosphatidylinositol-3 kinase inhibitor (LY294002, 50 micro M). These experiments suggest that cysteinyl leukotrienes play an augmentary role in human ASM migration. The phosphatidylinositol-3 kinase pathway is a key signaling mechanism in the chemotactic migration of ASM cells in response to cysteinyl leukotrienes.

C/EBPepsilon directs granulocytic-vs-monocytic lineage determination and confers chemotactic function via Hlx.

PubMed

Halene, Stephanie; Gaines, Peter; Sun, Hong; Zibello, Theresa; Lin, Sharon; Khanna-Gupta, Arati; Williams, Simon C; Perkins, Archibald; Krause, Diane; Berliner, Nancy

2010-02-01

Mutations in the CCAAT enhancer binding protein epsilon (C/EBPepsilon) gene have been identified in the cells of patients with neutrophil specific granule deficiency, a rare congenital disorder marked by recurrent bacterial infections. Their neutrophils, in addition to lacking specific granules required for normal respiratory burst activity, also lack normal phagocytosis and chemotaxis. Although the specific granule deficiency phenotype has been replicated in C/EBPepsilon(-/-) (knockout [KO]) mice, the mechanisms by which C/EBPepsilon mutations act to decrease neutrophil function are not entirely clear. In order to determine the role of C/EBPepsilon in neutrophil differentiation and migration, we generated immortalized progenitor cell lines from C/EBPepsilon KO and wild-type mice and performed expression and flow cytometric analysis and functional studies. Expression of lineage-specific cell surface antigens on our in vitro differentiated cell lines revealed persistent expression of monocytic markers on KO granulocytes. We verified this in primary murine peripheral blood and bone marrow cells. In addition, KO bone marrow had an increase in immature myeloid precursors at the common myeloid progenitor and granulocyte/monocyte progenitor levels, suggesting a critical role for C/EBPepsilon not only in granulocyte maturation beyond the promyelocyte stage, but also in the monocyte/granulocyte lineage decision. We found that restoration of Hlx (H2.0-like homeo box 1) expression, which was decreased in C/EBPepsilon KO cells, rescued chemotaxis, but not the other defects of C/EBPepsilon KO neutrophils. We show two new regulatory functions of C/EBPepsilon in myelopoiesis: in the absence of C/EBPepsilon, there is not only incomplete differentiation of granulocytes, but myelopoiesis is disrupted with the appearance of an intermediate cell type with monocyte and granulocyte features, and the neutrophils have abnormal chemotaxis. Restoration of expression of Hlx provides partial recovery of function; it has no effect on neutrophil maturation, but can completely ameliorate the chemotaxis defect in C/EBPepsilon KO cells. Copyright 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Chemotaxis of Molecular Dyes in Polymer Gradients in Solution.

PubMed

Guha, Rajarshi; Mohajerani, Farzad; Collins, Matthew; Ghosh, Subhadip; Sen, Ayusman; Velegol, Darrell

2017-11-08

Chemotaxis provides a mechanism for directing the transport of molecules along chemical gradients. Here, we show the chemotactic migration of dye molecules in response to the gradients of several different neutral polymers. The magnitude of chemotactic response depends on the structure of the monomer, polymer molecular weight and concentration, and the nature of the solvent. The mechanism involves cross-diffusion up the polymer gradient, driven by favorable dye-polymer interaction. Modeling allows us to quantitatively evaluate the strength of the interaction and the effect of the various parameters that govern chemotaxis.

Bifurcation in the chemotactic behavior of Physarum plasmodium

NASA Astrophysics Data System (ADS)

Shirakawa, Tomohiro; Gunji, Yukio-Pegio; Sato, Hiroshi; Tsubakino, Hiroto

2017-07-01

The plasmodium of true slime mold Physarum polycephalum is a unicellular and multinuclear giant amoeba. Since the cellular organism has some computational abilities, it is attracting much attention in the field of information science. However, previous studies have mainly focused on the optimization behavior of the plasmodium for a single-modality stimulus, and there are few studies on how the organism adapts to multi-modal stimuli. We stimulated the plasmodium with mixture of attractant and repellent stimuli, and we observed bifurcation in the chemotactic behavior of the plasmodium.

Neutrophil chemotaxis in response to TGF-beta isoforms (TGF-beta 1, TGF-beta 2, TGF-beta 3) is mediated by fibronectin.

PubMed

Parekh, T; Saxena, B; Reibman, J; Cronstein, B N; Gold, L I

1994-03-01

TGF-beta isoforms regulate numerous cellular functions including cell growth and differentiation, the cellular synthesis and secretion of extracellular matrix proteins, such as fibronectin (Fn), and the immune response. We have previously shown that TGF-beta 1 is the most potent chemoattractant described for human peripheral blood neutrophils (PMNs), suggesting that TGF-beta s may play a role in the recruitment of PMNs during the initial phase of the inflammatory response. In our current studies, we demonstrate that the maximal chemotactic response was attained near 40 fM for all mammalian TGF-beta isoforms. However, there was a statistically significant difference in migratory distance of the PMNs: TGF-beta 2 (556 microM) > TGF-beta 3 (463 microM) > TGF-beta 1 (380 microM) (beta 2: beta 3, p < or = 0.010; beta 3: beta 1, p < or = 0.04; beta 2: beta 1, p < or = 0.0012). A mAb to the cell binding domain (CBD) of Fn inhibited the chemotactic response to TGF-beta 1 and TGF-beta 3 by 63% and to TGF-beta 2 by 70%, whereas the response to FMLP, a classic chemoattractant, was only inhibited by 18%. In contrast, a mAb to a C-terminal epitope of Fn did not retard migration (< 1.5%). The Arg-gly-Asp-ser tetrapeptide inhibited chemotaxis by approximately the same extent as the anti-CBD (52 to 83%). Furthermore, a mAb against the VLA-5 integrin (VLA-5; Fn receptor) also inhibited TGF-beta-induced chemotaxis. These results indicate that chemotaxis of PMNs in response to TGF-beta isoforms is mediated by the interaction of the Arg-gly-Asp-ser sequence in the CBD of Fn with an integrin on the PMN cell surface, primarily the VLA-5 integrin. TGF-beta isoforms also elicited the release of cellular Fn from PMNs; we observed a 2.3-fold increase in Fn (389 to 401 ng/ml) in the supernatants of TGF-beta-stimulated PMNs compared with unstimulated cells (173.6 ng/ml). The concentration of TGF-beta required to cause maximal release of Fn from PMNs (4000 fM) is a concentration at which TGF-beta is no longer chemotactic, suggesting that PMNs only use Fn that is constitutively expressed for migration. At higher concentrations of TGF-beta, the Fn released may accumulate basal to the cell, ultimately retarding cellular migration and modulating the chemotactic response.

Effect of Porous Media Particle Size on Bacterial Motility and Chemotaxis

NASA Astrophysics Data System (ADS)

Olson, M. S.; Smith, J. A.; Ford, R. M.; Fernandez, E. J.

2003-12-01

Many soil-inhabiting bacteria that degrade chemical contaminants are both motile and chemotactic. Chemotaxis refers to the ability of bacteria to sense pollutant concentration gradients in water and preferentially swim toward regions of high pollutant concentration, and is thought to be important in guiding subsurface microbial populations toward chemical contaminants. Bacterial motion consists of a series of smooth-swimming runs interrupted by changes in direction. In the presence of a chemical gradient, bacteria bias their frequency of changing direction and demonstrate longer run lengths in the direction of increasing attractant concentration. One concern when studying bacterial chemotaxis in porous media is that in small pores, the porous media may interrupt the extended run lengths of bacteria swimming in the direction of a positive chemical gradient. The purpose of this study is to examine how a decrease in particle size affects the motility and chemotactic response of bacteria traveling through porous media. We employ an innovative technique for noninvasive visualization of changes in bacterial density distributions in a packed column as a function of time. Paramagnetic magnetite particles are attached to the surface of Pseudomonas putida F1 cells using an antibody. Bacterial distributions within a column of glass-coated polystyrene beads are imaged using magnetic resonance imaging (MRI), with a spatial resolution of 300 μ m. Experiments are conducted with both 250-300 μ m beads and 90-150 μ m beads. Bacteria labeled with magnetite are introduced into a specially designed chromatography column packed with glass-coated polystyrene beads. Bacterial migration is monitored over time using MRI, with and without the presence of a chemical gradient of trichloroethylene (TCE). Comparisons of the motility and chemotactic transport coefficients for Pseudomonas putida F1 cells traveling through different-sized samples of porous media in the presence of TCE will be presented and discussed. Results suggest a decrease in both motility and chemotaxis in the smaller-sized porous media.

Architecture of conference control functions

NASA Astrophysics Data System (ADS)

Kausar, Nadia; Crowcroft, Jon

1999-11-01

Conference control is an integral part in many-to-many communications that is used to manage and co-ordinate multiple users in conferences. There are different types of conferences which require different types of control. Some of the features of conference control may be user invoked while others are for internal management of a conference. In recent years, ITU (International Telecommunication Union) and IETF (Internet Engineering Task Force) have standardized two main models of conferencing, each system providing a set of conference control functionalities that are not easily provided in the other one. This paper analyzes the main activities appropriate for different types of conferences and presents an architecture for conference control called GCCP (Generic Conference Control Protocol). GCCP interworks different types of conferencing and provides a set of conference control functions that can be invoked by users directly. As an example of interworking, interoperation of IETF's SIP and ITU's H.323 call control functions have been examined here. This paper shows that a careful analysis of a conferencing architecture can provide a set of control functions essential for any group communication model that can be extensible if needed.

Differential targeting of Gbetagamma-subunit signaling with small molecules.

PubMed

Bonacci, Tabetha M; Mathews, Jennifer L; Yuan, Chujun; Lehmann, David M; Malik, Sundeep; Wu, Dianqing; Font, Jose L; Bidlack, Jean M; Smrcka, Alan V

2006-04-21

G protein betagamma subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gbetagamma subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gbetagamma subunit functions. Several compounds bound to Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.

LEGO bricks used as chemotactic chambers: evaluation by a computer-assisted image analysis technique.

PubMed

Azzarà, A; Chimenti, M

2004-01-01

One of the main techniques used to explore neutrophil motility, employs micropore filters in chemotactic chambers. Many new models have been proposed, in order to perform multiple microassays in a rapid, inexpensive and reproducible way. In this work, LEGO bricks have been used as chemotactic chambers in the evaluation of neutrophil random motility and chemotaxis and compared with conventional Boyden chambers in a "time-response" experiment. Neutrophil motility throughout the filters was evaluated by means of an image-processing workstation, in which a dedicated algorithm recognizes and counts the cells in several fields and focal planes throughout the whole filter; correlates counts and depth values; performs a statistical analysis of data; calculates the true value of neutrophil migration; determines the distribution of cells; and displays the migration pattern. By this method, we found that the distances travelled by the cells in conventional chambers and in LEGO bricks were perfectly identical, both in random migration and under chemotactic conditions. Moreover, no interference with the physiological behaviour of neutrophils was detectable. In fact, the kinetics of migration was identical both in random migration (characterized by a gaussian pattern) and in chemotaxis (characterized by a typical stimulation peak, previously identified by our workstation). In conclusion, LEGO bricks are extremely precise devices. They are simple to use and allow the use of small amounts of chemoattractant solution and cell suspension, supplying by itself a triplicate test. LEGO bricks are inexpensive, fast and suitable for current diagnostic activity or for research investigations in every laboratory.

Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP.

PubMed Central

Richter, J; Andersson, R; Edvinsson, L; Gullberg, U

1992-01-01

The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP. Images Figure 3 PMID:1282494

Motility analysis of bacteria-based microrobot (bacteriobot) using chemical gradient microchamber.

PubMed

Park, Daechul; Park, Sung Jun; Cho, Sunghoon; Lee, Yeonkyung; Lee, Yu Kyung; Min, Jung-Joon; Park, Bang Ju; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

2014-01-01

A bacteria-based microrobot (bacteriobot) was proposed and investigated as a new type of active drug delivery system because of its useful advantages, such as active tumor targeting, bacteria-mediated tumor diagnosis, and therapy. In this study, we fabricated a bacteriobot with enhanced motility by selective attachment of flagellar bacteria (Salmonella typhimurium). Through selective bovine serum albumin (BSA) pattering on hydrophobic polystyrene (PS) microbeads, many S. typhimurium could be selectively attached only on the unpatterned surface of PS microbead. For the evaluation of the chemotactic motility of the bacteriobot, we developed a microfluidic chamber which can generate a stable concentration gradient of bacterial chemotactic chemicals. Prior to the evaluation of the bacteriobot, we first evaluated the directional chemotactic motility of S. typhimurium using the proposed microfluidic chamber, which contained a bacterial chemo-attractant (L-aspartic acid) and a chemo-repellent (NiSO4 ), respectively. Compared to density of the control group in the microfluidic chamber without any chemical gradient, S. typhimurium increased by about 16% in the L-aspartic acid gradient region and decreased by about 22% in the NiSO4 gradient region. Second, we evaluated the bacteriobot's directional motility by using this microfluidic chamber. The chemotactic directional motility of the bacteriobot increased by 14% and decreased by 13% in the concentration gradients of L-aspartic acid and NiSO4 , respectively. These results confirm that the bacteriobot with selectively patterned S. typhimurium shows chemotaxis motility very similar to that of S. typhimurium. Moreover, the directional motilities of the bacteria and bacteriobot could be demonstrated quantitatively through the proposed microfluidic chamber. © 2013 Wiley Periodicals, Inc.

A chemotactic signaling surface on CheY defined by suppressors of flagellar switch mutations.

PubMed Central

Roman, S J; Meyers, M; Volz, K; Matsumura, P

1992-01-01

CheY is the response regulator protein that interacts with the flagellar switch apparatus to modulate flagellar rotation during chemotactic signaling. CheY can be phosphorylated and dephosphorylated in vitro, and evidence indicates that CheY-P is the activated form that induces clockwise flagellar rotation, resulting in a tumble in the cell's swimming pattern. The flagellar switch apparatus is a complex macromolecular structure composed of at least three gene products, FliG, FliM, and FliN. Genetic analysis of Escherichia coli has identified fliG and fliM as genes in which mutations occur that allele specifically suppress cheY mutations, indicating interactions among these gene products. We have generated a class of cheY mutations selected for dominant suppression of fliG mutations. Interestingly, these cheY mutations dominantly suppressed both fliG and fliM mutations; this is consistent with the idea that the CheY protein interacts with both switch gene products during signaling. Biochemical characterization of wild-type and suppressor CheY proteins did not reveal altered phosphorylation properties or evidence for phosphorylation-dependent CheY multimerization. These data indicate that suppressor CheY proteins are specifically altered in the ability to transduce chemotactic signals to the switch at some point subsequent to phosphorylation. Physical mapping of suppressor amino acid substitutions on the crystal structure of CheY revealed a high degree of spatial clustering, suggesting that this region of CheY is a signaling surface that transduces chemotactic signals to the switch. Images PMID:1400175

Feeding ducks, bacterial chemotaxis, and the Gini index

NASA Astrophysics Data System (ADS)

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.

Chemotaxis of Amoeba proteus in the developing pH gradient within a pocket-like chamber studied with the computer assisted method.

PubMed

Korohoda, W; Golda, J; Sroka, J; Wojnarowicz, A; Jochym, P; Madeja, Z

1997-01-01

A new "U" shaped, pocket-like chamber was used to observe the chemotactic responses of individual cells. This method permits monitoring of both the development of the concentration gradient of a tested substance and cell locomotion. We investigated the chemotactic responses of Amoeba proteus and observed that the amoebae moved in positively and negatively developing [H+] gradients towards the solution of lower pH in a pH range 5.75-7.75. The chemotactic response of amoebae to [H+] gradients required the presence of extracellular calcium ions. It was blocked and random locomotion was restored by the replacement of calcium with magnesium in the cell medium. Time-lapse video recording and data processing were accomplished with computer-assisted methods. This made it possible to compare selected methods of data presentation and analysis for cells locomoting in isotropic and anisotropic conditions. The cell trajectories were determined and displayed in circular diagrams, lengths of cell tracks and final cell displacements were estimated and a few parameters characterizing cell locomotion were computed.

Streptolysin O Inhibition of Neutrophil Chemotaxis and Mobility: Nonimmune Phenomenon with Species Specificity

PubMed Central

Van Epps, Dennis E.; Andersen, Burton R.

1974-01-01

The effects of streptolysin O (SO) (1 to 4 hemolytic units) on the mobility of neutrophilic leukocytes from humans, baboons, sheep, and rabbits were compared. After SO treatment, chemotaxis and random mobility of human neutrophils were markedly suppressed, baboon and sheep neutrophils were partially suppressed, and rabbit neutrophils were unaffected and demonstrated normal chemotaxis and mobility. The amounts of SO used in the mobility studies caused no leukocyte lysis or trypan blue uptake by human, baboon, or sheep cells, and minimal lysis or trypan blue uptake by rabbit cells. The possible involvement of immune mediators in the observed inhibition of human neutrophils was considered and excluded by the following studies. White blood cells from humans with humoral or cellular immune deficiencies responded in a manner similar to normal human cells; supernatant solutions from SO-treated human white blood cells did not contain a chemotactic suppressor; preincubation of SO with cholesterol (an inhibitor of SO hemolytic activity) caused loss of the chemotactic suppressive effect of the toxin on human leukocytes; and leukocytes from rabbits preimmunized with SO remained refractory to chemotactic suppression. Images PMID:4128632

Endocrine-immune interactions in human endometrium.

PubMed

Kayisli, U A; Guzeloglu-Kayisli, O; Arici, A

2004-12-01

The immune system is a complex entity designed to eliminate foreign intruding antigens and is influenced by and, in turn, influences the function of the reproductive system. Despite the widespread associations between immunology and reproductive medicine, the study of system interactions remains in its infancy. Many diverse facts are accumulating, and pieces of the puzzle are becoming available to provide a clearer picture. In this review article, we focus on the interactions between endocrine and immune systems in the human endometrium. Understanding the molecular pathways in endocrine-immune interactions in the human endometrium is crucial to understand events such as menstrual bleeding, tissue repair and regeneration, inflammation, angiogenesis, blastocyst implantation, and progression of pregnancy. These events require a balanced regulation of endometrial differentiation, proliferation, cell survival, leukocyte recruitment, apoptosis, and angiogenesis by sex steroids. In this review, we first outline the role of survival factors such as phosphoinositol 3-kinase/protein kinase B, PTEN, NFkappaB, and apoptotic molecules (Fas-FasL, Bcl-2). We then discuss their regulation by estrogen and progesterone in the endometrium. We present evidence for direct and/or indirect roles of steroid hormones on the expression of chemotactic cytokines (interleukin-8 and monocyte chemotactic protein-1) and on the survival versus apoptosis of resident endometrial cells (stromal, epithelial, and endothelial cells) and nonresident cells (leukocytes).

Unique mechanism of Helicobacter pylori for colonizing the gastric mucus.

PubMed

Yoshiyama, H; Nakazawa, T

2000-01-01

Helicobacter pylori is a human gastric pathogen causing chronic infection. Urease and motility using flagella are essential factors for its colonization. Urease of H. pylori exists both on the surface and in the cytoplasm, and is involved in neutralizing gastric acid and in chemotactic motility. H. pylori senses the concentration gradients of urea in the gastric mucus layer, then moves toward the epithelial surface by chemotactic movement. The energy source for the flagella movement is the proton motive force. The hydrolysis of urea by the cytoplasmic urease possibly generates additional energy for the flagellar rotation in the mucus gel layer.

Verification of epigenetic inheritance in a unicellular model system: multigenerational effects of hormonal imprinting.

PubMed

Kőhidai, László; Lajkó, Eszter; Pállinger, Eva; Csaba, György

2012-10-01

The unicellular Tetrahymena has receptors for hormones of higher vertebrates, produces these hormones, and their signal pathways are similar. The first encounter with a hormone in higher dose provokes the phenomenon of hormonal imprinting, by which the reaction of the cell is quantitatively modified. This modification is transmitted to the progeny generations. The duration of the single imprinter effect of two representative signal molecules, insulin and 5-HT (5-hydroxytryptamine), in two concentrations (10(-6) and 10(-15) M) were studied. The effects of imprinting were followed in 5 physiological indices: (i) insulin binding, (ii) 5-HT synthesis, (iii) swimming behaviour, (iv) cell growth and (v) chemotaxis in progeny generations 500 and 1000. The result of each index was different from the non-imprinted control functions, growth rate, swimming behaviour and chemotactic activity to insulin being enhanced, while others, e.g. synthesis and chemotactic responsiveness of 5-HT and the binding of insulin were reduced. This means that a function-specific heritable epigenetic change during imprinting occurs, and generally a single encounter with a femtomolar hormone concentration is enough for provoking durable and heritable imprinting in Tetrahymena. The experiments demonstrate the possibility of epigenetic effects at a unicellular level and call attention to the possibility that the character of unicellular organisms has changed through to the present day due to an enormous amount of non-physiological imprinter substances in their environment. The results - together with results obtained earlier in mammals - point to the validity of epigenetic imprinting effects throughout the animal world.

The calcium-activated potassium channel KCa3.1 plays a central role in the chemotactic response of mammalian neutrophils

PubMed Central

Henríquez, C.; Riquelme, T. T.; Vera, D.; Julio-Kalajzić, F.; Ehrenfeld, P.; Melvin, J. E.; Figueroa, C. D.; Sarmiento, J.; Flores, C. A.

2017-01-01

Aim Neutrophils are the first cells to arrive at sites of injury. Nevertheless, many inflammatory diseases are characterized by an uncontrolled infiltration and action of these cells. Cell migration depends on volume changes that are governed by ion channel activity, but potassium channels in neutrophil have not been clearly identified. We aim to test whether KCa3.1 participates in neutrophil migration and other relevant functions of the cell. Methods Cytometer and confocal measurements to determine changes in cell volume were used. Cells isolated from human, mouse and horse were tested for KCa3.1-dependent chemotaxis. Chemokinetics, calcium handling and release of reactive oxygen species were measured to determine the role of KCa3.1 in those processes. A mouse model was used to test for neutrophil recruitment after acute lung injury in vivo. Results We show for the first time that KCa3.1 is expressed in mammalian neutrophils. When the channel is inhibited by a pharmacological blocker or by genetic silencing, it profoundly affects cell volume regulation, and chemotactic and chemokinetic properties of the cells. We also demonstrated that pharmacological inhibition of KCa3.1 did not affect calcium entry or reactive oxygen species production in neutrophils. Using a mouse model of acute lung injury, we observed that Kca3.1−/− mice are significantly less effective at recruiting neutrophils into the site of inflammation. Conclusions These results demonstrate that KCa3.1 channels are key actors in the migration capacity of neutrophils, and its inhibition did not affect other relevant cellular functions. PMID:26138196

Induction of Macrophage Chemotaxis by Aortic Extracts from Patients with Marfan Syndrome Is Related to Elastin Binding Protein

PubMed Central

Guo, Gao; Gehle, Petra; Doelken, Sandra; Martin-Ventura, José Luis; von Kodolitsch, Yskert; Hetzer, Roland; Robinson, Peter N.

2011-01-01

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). PMID:21647416

Neural differentiation of mesenchymal stem cells influences chemotactic responses to HGF.

PubMed

Zheng, Bing; Wang, Chunyan; He, Lihong; Xu, Xiaojing; Qu, Jing; Hu, Jun; Zhang, Huanxiang

2013-01-01

Recently, mesenchymal stem cells (MSCs) have been extensively used for cell-based therapies in neuronal degenerative disease. Although much effort has been devoted to the delineation of factors involved in the migration of MSCs, the relationship between the chemotactic responses and the differentiation status of these cells remains elusive. Here, we report that MSCs in varying neural differentiation states display different chemotactic responses to hepatocyte growth factor (HGF): first, the number of chemotaxing MSCs and the optimal concentrations of HGF that induced the peak migration varied greatly; second, time-lapse video analysis showed that MSCs in certain differentiation state migrated more efficiently toward HGF; third, the phosphorylation levels of Akt, ERK1/2, SAPK/JNK, and p38MAPK were closely related to the differentiation levels of MSCs subjected to HGF; and finally, although inhibition of ERK1/2 signaling significantly attenuated HGF-stimulated transfilter migration of both undifferentiated and differentiating MSCs, abolishment of PI3K/Akt, p38MAPK, or SAPK/JNK signaling only decreased the number of migrated cells in certain differentiation state(s). Blocking of PI3K/Akt or MAPK signaling impaired the migration efficiency and/or speed, the extent of which depends on the cell differentiation states. Meanwhile, F-actin rearrangement, which is essential for MSCs chemotaxis, was induced by HGF, and the time points of cytoskeletal reorganization were different among these cells. Collectively, these results demonstrate that neural differentiation of MSCs influences their chemotactic responses to HGF: MSCs in varying differentiation states possess different migratory capacities, thereby shedding light on optimization of the therapeutic potential of MSCs to be employed for neural regeneration after injury. Copyright © 2012 Wiley Periodicals, Inc.

Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust-induced airway obstruction.

PubMed

Park, H; Jung, K; Kang, K; Nahm, D; Cho, S; Kim, Y

1999-04-01

The pathogenic mechanism of grain dust (GD)-induced occupational asthma (OA) remains unclear. To understand further the mechanism of GD-induced OA. Fifteen employees working in a same GD industry, complaining of work-related respiratory symptoms, were enrolled and were divided into two groups according to the GD-bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme-linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method. For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD-BPT in group III subjects (P < 0.05, respectively), while no significant changes were noted in group II subjects (P > 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti-IgG4 antibodies was noted in all three groups. These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD-induced occupational asthma.

Differential Targeting of Gβγ-Subunit Signaling with Small Molecules

NASA Astrophysics Data System (ADS)

Bonacci, Tabetha M.; Mathews, Jennifer L.; Yuan, Chujun; Lehmann, David M.; Malik, Sundeep; Wu, Dianqing; Font, Jose L.; Bidlack, Jean M.; Smrcka, Alan V.

2006-04-01

G protein βγ subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gβγ subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gβγ subunit functions. Several compounds bound to Gβγ subunits with affinities from 0.1 to 60 μM and selectively modulated functional Gβγ-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.

Optical tweezers for studying taxis in parasites

NASA Astrophysics Data System (ADS)

de Thomaz, A. A.; Fontes, A.; Stahl, C. V.; Pozzo, L. Y.; Ayres, D. C.; Almeida, D. B.; Farias, P. M. A.; Santos, B. S.; Santos-Mallet, J.; Gomes, S. A. O.; Giorgio, S.; Feder, D.; Cesar, C. L.

2011-04-01

In this work we present a methodology to measure force strengths and directions of living parasites with an optical tweezers setup. These measurements were used to study the parasites chemotaxis in real time. We observed behavior and measured the force of: (i) Leishmania amazonensis in the presence of two glucose gradients; (ii) Trypanosoma cruzi in the vicinity of the digestive system walls, and (iii) Trypanosoma rangeli in the vicinity of salivary glands as a function of distance. Our results clearly show a chemotactic behavior in every case. This methodology can be used to study any type of taxis, such as chemotaxis, osmotaxis, thermotaxis, phototaxis, of any kind of living microorganisms. These studies can help us to understand the microorganism sensory systems and their response function to these gradients.

'Extremotaxis': computing with a bacterial-inspired algorithm.

PubMed

Nicolau, Dan V; Burrage, Kevin; Nicolau, Dan V; Maini, Philip K

2008-01-01

We present a general-purpose optimization algorithm inspired by "run-and-tumble", the biased random walk chemotactic swimming strategy used by the bacterium Escherichia coli to locate regions of high nutrient concentration The method uses particles (corresponding to bacteria) that swim through the variable space (corresponding to the attractant concentration profile). By constantly performing temporal comparisons, the particles drift towards the minimum or maximum of the function of interest. We illustrate the use of our method with four examples. We also present a discrete version of the algorithm. The new algorithm is expected to be useful in combinatorial optimization problems involving many variables, where the functional landscape is apparently stochastic and has local minima, but preserves some derivative structure at intermediate scales.

An Ultrasensitive Bacterial Motor Revealed by Monitoring Signaling Proteins in Single Cells

NASA Astrophysics Data System (ADS)

Cluzel, Philippe; Surette, Michael; Leibler, Stanislas

2000-03-01

Understanding biology at the single-cell level requires simultaneous measurements of biochemical parameters and behavioral characteristics in individual cells. Here, the output of individual flagellar motors in Escherichia coli was measured as a function of the intracellular concentration of the chemotactic signaling protein. The concentration of this molecule, fused to green fluorescent protein, was monitored with fluorescence correlation spectroscopy. Motors from different bacteria exhibited an identical steep input-output relation, suggesting that they actively contribute to signal amplification in chemotaxis. This experimental approach can be extended to quantitative in vivo studies of other biochemical networks.

Defective neutrophil chemotaxis in juvenile periodontitis.

PubMed Central

Clark, R A; Page, R C; Wilde, G

1977-01-01

Neutrophil chemotaxis was evaluated in nine patients with juvenile periodontitis, with normal subjects and patients with the adult form of periodontitis as controls. Defective chemotactic responses were observed in neutrophils from seven of nine juvenile patients, and a reduced level of complement-derived chemotactic activity was demonstrated in serum from four patients. These determinations were normal in all the patients with adult periodontitis. Serum from five of the juvenile patients contained a heat-stable, non-dialyzable factor that markedly inhibited the chemotaxis of normal neutrophils. Thus the characteristic tissue destruction seen in juvenile periodontitis may be, at least in part, a consequence of a failure of host defense mechanisms. PMID:591063

In vitro inhibitory effects of Moringa oleifera leaf extract and its major components on chemiluminescence and chemotactic activity of phagocytes.

PubMed

Vongsak, Boonyadist; Gritsanapan, Wandee; Wongkrajang, Yuvadee; Jantan, Ibrahim

2013-11-01

The ethanol extract of Moringa oleifera Lam. leaves and its major constituents, crypto-chlorogenic acid, quercetin 3-O-glucoside and kaempferol 3-O-glucoside, were investigated on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using a luminol-based chemiluminescence assay. The chemotactic migration of PMNs was also investigated using the Boyden chamber technique. The ethanol extract demonstrated inhibitory activities on the oxidative burst and the chemotactic migration of PMNs. Quercetin 3-O-glucoside, crypto-chlorogenic acid, and kaempferol 3-O-glucoside, isolated from the extract, expressed relatively strong inhibitory activity on the oxidative burst of PMNs with IC50 values of 4.1, 6.7 and 7.0 microM, respectively, comparable with that of aspirin. They also demonstrated strong inhibition of chemotatic migration of PMNs with IC50 values of 9.5, 15.9 and 18.2 microM, respectively. The results suggest that M. oleifera leaves could modulate the immune response of human phagocytes, linking to its ethnopharmacological use as an anti-inflammatory agent. The immunomodulating activity of the plant was mainly due to its major components.

p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis.

PubMed

Wang, Wei; Liu, Haijun; Dai, Xiaoniu; Fang, Shencun; Wang, Xingang; Zhang, Yingming; Yao, Honghong; Zhang, Xilong; Chao, Jie

2015-11-18

Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear. Here, to elucidate the role of p53 in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Experiments using primary cultured adult human pulmonary fibroblasts led to the following results: 1) SiO2 treatment resulted in a rapid and sustained increase in p53 and PUMA protein levels; 2) the MAPK and PI3K pathways were involved in the SiO2-induced alteration of p53 and PUMA expression; and 3) RNA interference targeting p53 and PUMA prevented the SiO2-induced increases in fibroblast activation and migration. Our study elucidated a link between SiO2-induced p53/PUMA expression in fibroblasts and cell migration, thereby providing novel insight into the potential use of p53/PUMA in the development of novel therapeutic strategies for silicosis treatment.

Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice

PubMed Central

Yao, Longbiao; Yago, Tadayuki; Shao, Bojing; Liu, Zhenghui; Silasi-Mansat, Robert; Setiadi, Hendra; Lupu, Florea

2013-01-01

Neutrophils emigrate from venules to sites of infection or injury in response to chemotactic gradients. How these gradients form is not well understood. Some IL-6 family cytokines stimulate endothelial cells to express adhesion molecules and chemokines that recruit leukocytes. Receptors for these cytokines share the signaling subunit gp130. We studied knockout mice lacking gp130 in endothelial cells. Unexpectedly, gp130-deficient endothelial cells constitutively expressed more CXCL1 in vivo and in vitro, and even more upon stimulation with tumor necrosis factor-α. Mobilization of this increased CXCL1 from intracellular stores to the venular surface triggered β2 integrin–dependent arrest of neutrophils rolling on selectins but impaired intraluminal crawling and transendothelial migration. Superfusing CXCL1 over venules promoted neutrophil migration only after intravenously injecting mAb to CXCL1 to diminish its intravascular function or heparinase to release CXCL1 from endothelial proteoglycans. Remarkably, mice lacking gp130 in endothelial cells had impaired histamine-induced venular permeability, which was restored by injecting anti–P-selectin mAb to prevent neutrophil rolling and arrest. Thus, excessive CXCL1 expression in gp130-deficient endothelial cells augments neutrophil adhesion but hinders migration, most likely by disrupting chemotactic gradients. Our data define a role for endothelial cell gp130 in regulating integrin-dependent adhesion and de-adhesion of neutrophils during inflammation. PMID:24081661

Immune modulation of CD4+CD25+ regulatory T cells by zoledronic acid.

PubMed

Liu, Hsien; Wang, Shih-Han; Chen, Shin-Cheh; Chen, Ching-Ying; Lo, Jo-Lin; Lin, Tsun-Mei

2016-11-25

CD4 + CD25 + regulatory T (Treg) cells suppress tumor immunity by inhibiting immune cells. Manipulation of Treg cells represents a new strategy for cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed Treg-cell activity and activated inflammatory Th17 cells. However, the interaction between ZA and Treg cells remained unclear. This study investigated the immune modulation of Treg cells by ZA. Flow cytometry was used to analyze the phenotypic and immunosuppressive characteristics of Treg cells treated with ZA. Chemotactic migration was evaluated using transwell assays. Quantitative real-time PCR (qRT-PCR) was used to investigate the effect of ZA on the expression of suppressive molecules by Treg cells. Proliferation of isolated Treg cells in culture was inhibited by ZA, although ZA did not induce apoptosis. qRT-PCR and flow cytometry showed that ZA significantly downregulated the expression of CCR4, CTLA4, PD-1 and RANKL on Treg cells. Chemotactic migration and immunosuppressive functions were also significantly attenuated in Treg cells pretreated with ZA, and these effects were dose-dependent. Co-culture with Treg cells significantly increased the migration rate of breast cancer cells, while pretreatment of Treg cells with ZA attenuated this effect. Our findings demonstrated that ZA acted as an immune modulator by significantly inhibiting the expansion, migration, immunosuppressive function and pro-metastatic ability of Treg cells. Immunomodulation of Treg cells by ZA represents a new strategy for cancer therapy.

The calcium-activated potassium channel KCa3.1 plays a central role in the chemotactic response of mammalian neutrophils.

PubMed

Henríquez, C; Riquelme, T T; Vera, D; Julio-Kalajzić, F; Ehrenfeld, P; Melvin, J E; Figueroa, C D; Sarmiento, J; Flores, C A

2016-01-01

Neutrophils are the first cells to arrive at sites of injury. Nevertheless, many inflammatory diseases are characterized by an uncontrolled infiltration and action of these cells. Cell migration depends on volume changes that are governed by ion channel activity, but potassium channels in neutrophil have not been clearly identified. We aim to test whether KCa3.1 participates in neutrophil migration and other relevant functions of the cell. Cytometer and confocal measurements to determine changes in cell volume were used. Cells isolated from human, mouse and horse were tested for KCa3.1-dependent chemotaxis. Chemokinetics, calcium handling and release of reactive oxygen species were measured to determine the role of KCa3.1 in those processes. A mouse model was used to test for neutrophil recruitment after acute lung injury in vivo. We show for the first time that KCa3.1 is expressed in mammalian neutrophils. When the channel is inhibited by a pharmacological blocker or by genetic silencing, it profoundly affects cell volume regulation, and chemotactic and chemokinetic properties of the cells. We also demonstrated that pharmacological inhibition of KCa3.1 did not affect calcium entry or reactive oxygen species production in neutrophils. Using a mouse model of acute lung injury, we observed that Kca3.1(-/-) mice are significantly less effective at recruiting neutrophils into the site of inflammation. These results demonstrate that KCa3.1 channels are key actors in the migration capacity of neutrophils, and its inhibition did not affect other relevant cellular functions. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Polylysine as a functional biopolymer to couple gold nanorods to tumor-tropic cells.

PubMed

Borri, Claudia; Centi, Sonia; Ratto, Fulvio; Pini, Roberto

2018-05-31

The delivery of plasmonic particles, such as gold nanorods, to the tumor microenvironment has attracted much interest in biomedical optics for topical applications as the photoacoustic imaging and photothermal ablation of cancer. However, the systemic injection of free particles still crashes into a complexity of biological barriers, such as the reticuloendothelial system, that prevent their efficient biodistribution. In this context, the notion to exploit the inherent features of tumor-tropic cells for the creation of a Trojan horse is emerging as a plausible alternative. We report on a convenient approach to load cationic gold nanorods into murine macrophages that exhibit chemotactic sensitivity to track gradients of inflammatory stimuli. In particular, we compare a new model of poly-L-lysine-coated particles against two alternatives of cationic moieties that we have presented elsewhere, i.e. a small quaternary ammonium compound and an arginine-rich cell-penetrating peptide. Murine macrophages that are exposed to poly-L-lysine-coated gold nanorods at a dosage of 400 µM Au for 24 h undertake efficient uptake, i.e. around 3 pg Au per cell, retain the majority of their cargo until 24 h post-treatment and maintain around 90% of their pristine viability, chemotactic and pro-inflammatory functions. With respect to previous models of cationic coatings, poly-L-lysine is a competitive solution for the preparation of biological vehicles of gold nanorods, especially for applications that may require longer life span of the Trojan horse, say in the order of 24 h. This biopolymer combines the cost-effectiveness of small molecules and biocompatibility and efficiency of natural peptides and thus holds potential for translational developments.

Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

PubMed Central

Hradilova, Nada; Sadilkova, Lenka; Palata, Ondrej; Mysikova, Dagmar; Mrazkova, Hana; Lischke, Robert; Spisek, Radek; Adkins, Irena

2017-01-01

High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4+CD25+Foxp3+ T regulatory cells and stimulated IFN-γ-producing tumor antigen-specific CD4+ and CD8+ T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8+ and CD4+ T cell responses were detected in NSCLC patient’s against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8+ T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers. PMID:28187172

Chemotactic-based adaptive self-organization during colonial development

NASA Astrophysics Data System (ADS)

Cohen, Inon; Czirók, Andras; Ben-Jacob, Eshel

1996-02-01

Bacterial colonies have developed sophisticated modes of cooperative behavior which enable them to respond to adverse growth conditions. It has been shown that such behavior can be manifested in the development of complex colonial patterns. Certain bacterial species exhibit formation of branching patterns during colony development. Here we present a generic model to describe such patterning of swimming (tumbling) bacteria on agar surfaces. The model incorporates: (1) food diffusion, (2) reproduction and sporulation of the cells, (3) movement of the bacterial cells within a self-produced wetting fluid and (4) chemotactic signaling. As a plausible explanation for transitions between different branching morphologies, we propose an interplay between chemotaxis towards food, self-produced short range chemoattractant and long range chemorepellent.

Clusters, asters, and collective oscillations in chemotactic colloids

NASA Astrophysics Data System (ADS)

Saha, Suropriya; Golestanian, Ramin; Ramaswamy, Sriram

2014-06-01

The creation of synthetic systems that emulate the defining properties of living matter, such as motility, gradient-sensing, signaling, and replication, is a grand challenge of biomimetics. Such imitations of life crucially contain active components that transform chemical energy into directed motion. These artificial realizations of motility point in the direction of a new paradigm in engineering, through the design of emergent behavior by manipulating properties at the scale of the individual components. Catalytic colloidal swimmers are a particularly promising example of such systems. Here we present a comprehensive theoretical description of gradient-sensing of an individual swimmer, leading controllably to chemotactic or anti-chemotactic behavior, and use it to construct a framework for studying their collective behavior. We find that both the positional and the orientational degrees of freedom of the active colloids can exhibit condensation, signaling formation of clusters and asters. The kinetics of catalysis introduces a natural control parameter for the range of the interaction mediated by the diffusing chemical species. For various regimes in parameter space in the long-ranged limit our system displays precise analogs to gravitational collapse, plasma oscillations, and electrostatic screening. We present prescriptions for how to tune the surface properties of the colloids during fabrication to achieve each type of behavior.

Multi-phasic bi-directional chemotactic responses of the growth cone

PubMed Central

Naoki, Honda; Nishiyama, Makoto; Togashi, Kazunobu; Igarashi, Yasunobu; Hong, Kyonsoo; Ishii, Shin

2016-01-01

The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue. With biologically realistic sigmoidal dose-responses, our model predicted tri-phasic turning response depending on intracellular Ca2+ level, which was then experimentally confirmed by growth cone turning assays and Ca2+ imaging. Furthermore, we took a reverse-engineering analysis to identify balanced regulation between CaMKII (activator) and PP1 (inhibitor) and then the model performance was validated by reproducing turning assays with inhibitions of CaMKII and PP1. Thus, our study implies that the balance between activator and inhibitor underlies the multi-phasic bi-directional turning response of the growth cone. PMID:27808115

Bacteria foraging in turbulent waters

NASA Astrophysics Data System (ADS)

Taylor, John; Tang, Wenbo; Stocker, Roman

2009-11-01

Marine bacteria are the Ocean's recyclers, contributing to as much as 50% of the productivity of the marine food web. Bacteria forage on patches of dissolved nutrients using chemotaxis, the ability to swim up chemical gradients. As turbulence is ubiquitous in the Ocean, it is important to understand how turbulent flow conditions affect bacterial foraging. We used three-dimensional, isotropic direct numerical simulations coupled with a bacterial transport equation to address this problem. After the flow is continuously forced until it reaches a steady state, microscale nutrient patches are injected into the turbulent flow, and stirring produces thin nutrient filaments. Two populations of bacteria compete against each other: one population is motile and chemotactic (`active'), the other is non-motile (`passive'). The distribution of both populations is initially uniform. Chemotaxis allows active bacteria to cluster near the center of the nutrient filaments, increasing their nutrient uptake relative to passive bacteria. Increasing the turbulence intensity increases the short-term chemotactic advantage by quickly producing large gradients in the nutrient concentration, but also leads to rapid mixing of the nutrient field, which makes the chemotactic advantage short-lived. The results suggest that the evolutionary advantage of chemotaxis, based on the increase in nutrient uptake relative to the energetic cost of swimming, strongly depends on the turbulence level.

Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum

PubMed Central

Losada-Barragán, Monica; Umaña-Pérez, Adriana; Cuervo-Escobar, Sergio; Berbert, Luiz Ricardo; Porrozzi, Renato; Morgado, Fernanda N.; Mendes-da-Cruz, Daniella Areas; Savino, Wilson; Sánchez-Gómez, Myriam; Cuervo, Patricia

2017-01-01

Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered a primary risk factor for the development of clinical visceral leishmaniasis (VL). Protein malnutrition and infection with Leishmania infantum leads to lymphoid tissue disorganization, including changes in cellularity and lymphocyte subpopulations in the thymus and spleen. Here we report that protein malnutrition modifies thymic chemotactic factors by diminishing the CCL5, CXCL12, IGF1, CXCL9 and CXCL10 protein levels in infected animals. Nevertheless, T cells preserve their migratory capability, as they were able to migrate ex vivo in response to chemotactic stimuli, indicating that malnutrition may compromise the thymic microenvironment and alter in vivo thymocyte migration. Decrease in chemotactic factors protein levels was accompanied by an early increase in the parasite load of the spleen. These results suggest that the precondition of malnutrition is affecting the cell-mediated immune response to L. infantum by altering T cell migration and interfering with the capacity of protein-deprived animals to control parasite spreading and proliferation. Our data provide evidence for a disturbance of T lymphocyte migration involving both central and peripheral T-cells, which likely contribute to the pathophysiology of VL that occurs in malnourished individuals. PMID:28397794

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

NASA Astrophysics Data System (ADS)

Adadevoh, J.; Triolo, S.; Ramsburg, C. A.; Ford, R.

2015-12-01

The use of chemotactic bacteria in bioremediation has the potential to increase access to, and biotransformation of, contaminant mass within the subsurface environment. This laboratory-scale study aimed to understand and quantify the influence of chemotaxis on residence times of pollutant-degrading bacteria within homogeneous treatment zones. Focus was placed on a continuous flow sand-packed column system 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 non-chemotactic mutant strain, were simultaneously introduced into the sand-packed column at equal concentrations. Breakthrough curves obtained for the bacteria from column experiments conducted with and without naphthalene were used to quantify the effect of chemotaxis on transport parameters. In the presence of the chemoattractant, longitudinal dispersivity of PpG7 increased by a factor of 3 and percent recovery decreased from 21% to 12%. The results imply that pore-scale chemotaxis responses are evident at an interstitial fluid velocity of 1.7 m/d, 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.

Grain dust induces IL-8 production from bronchial epithelial cells: effect on neutrophil recruitment.

PubMed

Park, H S; Suh, J H; Kim, S S; Kwon, O J

2000-06-01

There have been several investigations suggesting an involvement of activated neutrophils in the development of grain dust (GD)-induced occupational asthma. Interleukin-8 in the sputa from GD-induced asthmatic patients increased significantly after the exposure to GD. To confirm IL-8 production from bronchial epithelial cells when exposed to GD, and to evaluate the role of IL-8 on neutrophil recruitment. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four different concentrations ranging from 1 to 200 microg/mL of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production and neutrophil chemotaxis, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant derived from subjects with GD-induced asthma exposed to 10 microg/mL of GD, and then compared with those without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. Neutrophil chemotactic activity of the culture supernatant was determined by modified Boyden chamber method. Interleukin-8 production and neutrophil chemotactic activity from bronchial epithelial cells significantly increased with additions of GD in a dose-dependent manner (P < .05, respectively), and were significantly augmented with additions of PBMC supernatant (P < .05, respectively) at each concentration. Close correlation was noted between neutrophil chemotactic activity and IL-8 level (r = 0.87, P < .05). Compared with the untreated sample, pre-treatment of anti-IL-8 antibody induced a significant suppression (up to 67.2%) of neutrophil chemotactic activity in a dose-dependent manner. These results suggest that IL-8 produced from bronchial epithelial cells may be a major cytokine, which induces neutrophil migration into the airways when exposed to GD.

Substrate-driven chemotactic assembly in an enzyme cascade.

PubMed

Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M; Gilson, Michael K; Butler, Peter J; Hess, Henry; Benkovic, Stephen J; Sen, Ayusman

2018-03-01

Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

Substrate-driven chemotactic assembly in an enzyme cascade

NASA Astrophysics Data System (ADS)

Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

2018-03-01

Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

Leukocyte subsets and neutrophil function after short-term spaceflight

NASA Technical Reports Server (NTRS)

Stowe, R. P.; Sams, C. F.; Mehta, S. K.; Kaur, I.; Jones, M. L.; Feeback, D. L.; Pierson, D. L.

1999-01-01

Changes in leukocyte subpopulations and function after spaceflight have been observed but the mechanisms underlying these changes are not well defined. This study investigated the effects of short-term spaceflight (8-15 days) on circulating leukocyte subsets, stress hormones, immunoglobulin levels, and neutrophil function. At landing, a 1.5-fold increase in neutrophils was observed compared with preflight values; lymphocytes were slightly decreased, whereas the results were variable for monocytes. No significant changes were observed in plasma levels of immunoglobulins, cortisol, or adrenocorticotropic hormone. In contrast, urinary epinephrine, norepinephrine, and cortisol were significantly elevated at landing. Band neutrophils were observed in 9 of 16 astronauts. Neutrophil chemotactic assays showed a 10-fold decrease in the optimal dose response after landing. Neutrophil adhesion to endothelial cells was increased both before and after spaceflight. At landing, the expression of MAC-1 was significantly decreased while L-selectin was significantly increased. These functional alterations may be of clinical significance on long-duration space missions.

Flagellar dynamics reveal the distribution of chemotactic signaling molecule CheY-P in E. coli

NASA Astrophysics Data System (ADS)

Bano, Roshni; Mears, Patrick; Chemla, Yann; Golding, Ido

E. colicells swim in a random walk consisting of ''runs'' - during which the flagella that propel the cell rotate counter-clockwise (CCW) - and ''tumbles''- during which one or more flagella rotate clockwise (CW). The tumbling frequency is modulated by the phosphorylation state of the signaling molecule CheY, which depends on the cell's environment. Phosphorylated CheY (CheY-P) binds to a flagellar motor and engenders a change in rotation state from CCW to CW. Despite advances in methods used to observe chemotactic signaling, it remains a challenge to measure the CheY-P level in cells directly. Here, we used an optical trap assay coupled with fluorescence microscopy to observe the dynamics of fluorescently labelled flagella in individual cells. By measuring the distribution of flagellar states in multi-flagellated cells and using our recent finding that each flagellar motor independently measures the cellular CheY-P concentration, we are able to extract the probability distribution of the CheY-P level in the cell. This analysis reveals the magnitude of fluctuations in chemotactic signaling in the live cell. We further investigate how this CheY-P distribution changes when cells encounter chemical gradients and perform chemotaxis. This work was supported by the National Science Foundation (NSF) through the Centre for Physics of Living Cells (CPLC).

Organic acids from root exudates of banana help root colonization of PGPR strain Bacillus amyloliquefaciens NJN-6

PubMed Central

Yuan, Jun; Zhang, Nan; Huang, Qiwei; Raza, Waseem; Li, Rong; Vivanco, Jorge M.; Shen, Qirong

2015-01-01

The successful colonization of plant growth promoting rhizobacteria (PGPR) in the rhizosphere is an initial and compulsory step in the protection of plants from soil-borne pathogens. Therefore, it is necessary to evaluate the role of root exudates in the colonization of PGPR. Banana root exudates were analyzed by high pressure liquid chromatography (HPLC) which revealed exudates contained several organic acids (OAs) including oxalic, malic and fumaric acid. The chemotactic response and biofilm formation of Bacillus amyloliquefaciens NJN-6 were investigated in response to OA’s found in banana root exudates. Furthermore, the transcriptional levels of genes involved in biofilm formation, yqxM and epsD, were evaluated in response to OAs via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results suggested that root exudates containing the OAs both induced the chemotaxis and biofilm formation in NJN-6. In fact, the strongest chemotactic and biofilm response was found when 50 μM of OAs were applied. More specifically, malic acid showed the greatest chemotactic response whereas fumaric acid significantly induced biofilm formation by a 20.7–27.3% increase and therefore biofilm formation genes expression. The results showed banana root exudates, in particular the OAs released, play a crucial role in attracting and initiating PGPR colonization on the host roots. PMID:26299781

A Diffusion Approximation Based on Renewal Processes with Applications to Strongly Biased Run-Tumble Motion.

PubMed

Thygesen, Uffe Høgsbro

2016-03-01

We consider organisms which use a renewal strategy such as run-tumble when moving in space, for example to perform chemotaxis in chemical gradients. We derive a diffusion approximation for the motion, applying a central limit theorem due to Anscombe for renewal-reward processes; this theorem has not previously been applied in this context. Our results extend previous work, which has established the mean drift but not the diffusivity. For a classical model of tumble rates applied to chemotaxis, we find that the resulting chemotactic drift saturates to the swimming velocity of the organism when the chemical gradients grow increasingly steep. The dispersal becomes anisotropic in steep gradients, with larger dispersal across the gradient than along the gradient. In contrast to one-dimensional settings, strong bias increases dispersal. We next include Brownian rotation in the model and find that, in limit of high chemotactic sensitivity, the chemotactic drift is 64% of the swimming velocity, independent of the magnitude of the Brownian rotation. We finally derive characteristic timescales of the motion that can be used to assess whether the diffusion limit is justified in a given situation. The proposed technique for obtaining diffusion approximations is conceptually and computationally simple, and applicable also when statistics of the motion is obtained empirically or through Monte Carlo simulation of the motion.

Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells

PubMed Central

Pace, Elisabetta; Ferraro, Maria; Siena, Liboria; Melis, Mario; Montalbano, Angela M; Johnson, Malcolm; Bonsignore, Maria R; Bonsignore, Giovanni; Gjomarkaj, Mark

2008-01-01

Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Toll-like receptor (TLR) expression and activation in a human bronchial epithelial cell line (16-HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor-κB (NF-κB) activation, the release of interleukin-8 (IL-8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced both NF-κB and ERK1/2 activation. The combined exposure of 16-HBE to CSE and LPS was associated with ERK activation rather than NF-κB activation and with a further increase of IL-8 release and of chemotactic activity toward neutrophils. Furthermore, CSE decreased the constitutive interferon-inducible protein-10 (IP-10) release and counteracted the effect of LPS in inducing both the IP-10 release and the chemotactic activity toward lymphocytes. In conclusion, cigarette smoke, by altering the expression and the activation of TLR4 via the preferential release of IL-8, may contribute to the accumulation of neutrophils within the airways of smokers. PMID:18217953

Effect of aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing amino acids on Leishmania spp. chemotaxis.

PubMed

Diaz, E; Zacarias, A K; Pérez, S; Vanegas, O; Köhidai, L; Padrón-Nieves, M; Ponte-Sucre, A

2015-11-01

In the sand-fly mid gut, Leishmania promastigotes are exposed to acute changes in nutrients, e.g. amino acids (AAs). These metabolites are the main energy sources for the parasite, crucial for its differentiation and motility. We analysed the migratory behaviour and morphological changes produced by aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing AAs in Leishmania amazonensis and Leishmania braziliensis and demonstrated that L-methionine (10-12 m), L-tryptophan (10-11 m), L-glutamine and L-glutamic acid (10-6 m), induced positive chemotactic responses, while L-alanine (10-7 m), L-methionine (10-11 and 10-7 m), L-tryptophan (10-11 m), L-glutamine (10-12 m) and L-glutamic acid (10-9 m) induced negative chemotactic responses. L-proline and L-cysteine did not change the migratory potential of Leishmania. The flagellum length of L. braziliensis, but not of L. amazonensis, decreased when incubated in hyperosmotic conditions. However, chemo-repellent concentrations of L-alanine (Hypo-/hyper-osmotic conditions) and L-glutamic acid (hypo-osmotic conditions) decreased L. braziliensis flagellum length and L-methionine (10-11 m, hypo-/hyper-osmotic conditions) decreased L. amazonensis flagellum length. This chemotactic responsiveness suggests that Leishmania discriminate between slight concentration differences of small and structurally closely related molecules and indicates that besides their metabolic effects, AAs play key roles linked to sensory mechanisms that might determine the parasite's behaviour.

Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.

PubMed Central

Nemoto, E; Nakamura, M; Shoji, S; Horiuchi, H

1997-01-01

Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP. PMID:9284170

A supplemented soft agar chemotaxis assay demonstrates the Helicobacter pylori chemotactic response to zinc and nickel

PubMed Central

Sanders, Lisa; Andermann, Tessa M.

2013-01-01

Directed motility, or chemotaxis, is required for Helicobacter pylori to establish infection in the stomach, although the full repertoire of this bacterium’s chemotactic responses is not yet known. Here we report that H. pylori responds to zinc as an attractant and nickel as a repellent. To reach this conclusion, we employed both a temporal chemotaxis assay based on bacterial reversals and a supplemented soft agar spatial assay. We refined the temporal assay using a previously described chemorepellent, acid, and found that H. pylori requires rich media with serum to maintain optimal swimming motility. Surprisingly, we found that some strains respond to acid as an attractant, and that the TlpC chemoreceptor correlated with whether acid was sensed as an attractant or repellent. Using this same assay, we detected weak repellent responses to nickel and copper, and a varied response to zinc. We thus developed an alternative spatial chemotactic assay called the supplemented soft agar assay, which utilizes soft agar medium supplemented with the test compound. With Escherichia coli, the attractant serine slowed overall bacterial migration, while the repellent nickel increased the speed of overall migration. In H. pylori we detected slowed migration with doubled tryptone media, as well as zinc, consistent with an attractant response. In contrast, nickel increased migration, consistent with repulsion. PMID:23139399

Misbalanced CXCL12 and CCL5 Chemotactic Signals in Vitiligo Onset and Progression.

PubMed

Rezk, Ahmed F; Kemp, Daria Marley; El-Domyati, Moetaz; El-Din, Wael Hosam; Lee, Jason B; Uitto, Jouni; Igoucheva, Olga; Alexeev, Vitali

2017-05-01

Generalized nonsegmental vitiligo is often associated with the activation of melanocyte-specific autoimmunity. Because chemokines play an important role in the maintenance of immune responses, we examined chemotactic signatures in cultured vitiligo melanocytes and skin samples of early (≤2 months) and advanced (≥6 months) vitiligo. Analysis showed that melanocytes in early lesions have altered expression of several chemotaxis-associated molecules, including elevated secretion of CXCL12 and CCL5. Higher levels of these chemokines coincided with prominent infiltration of the skin with antigen presenting cells (APCs) and T cells. Most of the intralesional APCs expressed the CD86 maturation marker and co-localized with T cells, particularly in early vitiligo lesions. These observations were confirmed by in vivo animal studies showing preferential recruitment of APCs and T cells to CXCL12- and CCL5-expressing transplanted melanocytes, immunotargeting of the chemokine-positive cells, continuous loss of the pigment-producing cells from the epidermis, and development of vitiligo-like lesions. Taken together, our studies show that melanocyte-derived CXCL12 and CCL5 support APC and T-cell recruitment, antigen acquisition, and T-cell activation in early vitiligo and reinforce the role of melanocyte-derived CXCL12 and CCL5 in activation of melanocyte-specific immunity and suggest inhibition of these chemotactic axes as a strategy for vitiligo stabilization. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemotaxis and auto-chemotaxis of self-propelling artificial droplet swimmers

NASA Astrophysics Data System (ADS)

Jin, Chenyu; Krueger, Carsten; Maass, Corinna

Chemotaxis and auto-chemotaxis are key mechanisms in the dynamics of micro-organisms, e.g. in the acquisition of nutrients and in the communication between individuals, influencing the collective behavior. However, chemical signalling and the natural environment of biological swimmers are generally complex, making them hard to access analytically. Simple experimental systems showing similar features could provide vital insights. We present such a swimmer system, as well as controlled assays to study chemotactic effects quantitatively and reproducibly. In our experiments, we let auto-chemotactic droplet swimmers pass through bifurcating microfluidic channels and record anticorrelations between the branch choices of consecutive droplets. We present an analytical model based on balancing stochastic forces versus a diffusing chemical gradient matching the experimental data. supported by the DFG SPP 1726 ''Microswimmers'' and the MaxSynBio network.

Chemotactic Motility of Sperm in Shear

NASA Astrophysics Data System (ADS)

Guasto, Jeffrey S.; Riffell, Jeffrey A.; Zimmer, Richard K.; Stocker, Roman

2011-11-01

Chemical gradients are utilized by plants and animals in sexual reproduction to guide swimming sperm cells toward the egg. This process (``chemotaxis''), which can greatly increase the success of fertilization, is subject to interference by fluid flow, both in the bodily conduits of internal fertilizers (e.g. mammals) and in the aquatic environment of external fertilizers (e.g. benthic invertebrates). We studied the biomechanics of chemotaxing sea urchin spermatozoa using microfluidic devices, which allow for the precise and independent control of attractant gradients and fluid shear. We captured swimming trajectories and flagellar beat patterns using high-speed video-microscopy, to detect chemotactic responses and measure the effect of fluid forces on swimming. This work will ultimately help us to understand how swimming sperm cells actively navigate natural chemoattractant gradients for successful fertilization.

Optimal chemotactic responses in stochastic environments

PubMed Central

Godány, Martin

2017-01-01

Although the “adaptive” strategy used by Escherichia coli has dominated our understanding of bacterial chemotaxis, the environmental conditions under which this strategy emerged is still poorly understood. In this work, we study the performance of various chemotactic strategies under a range of stochastic time- and space-varying attractant distributions in silico. We describe a novel “speculator” response in which the bacterium compare the current attractant concentration to the long-term average; if it is higher then they tumble persistently, while if it is lower than the average, bacteria swim away in search of more favorable conditions. We demonstrate how this response explains the experimental behavior of aerobically-grown Rhodobacter sphaeroides and that under spatially complex but slowly-changing nutrient conditions the speculator response is as effective as the adaptive strategy of E. coli. PMID:28644830

Micromotors Powered by Enzyme Catalysis.

PubMed

Dey, Krishna K; Zhao, Xi; Tansi, Benjamin M; Méndez-Ortiz, Wilfredo J; Córdova-Figueroa, Ubaldo M; Golestanian, Ramin; Sen, Ayusman

2015-12-09

Active biocompatible systems are of great current interest for their possible applications in drug or antidote delivery at specific locations. Herein, we report the synthesis and study of self-propelled microparticles powered by enzymatic reactions and their directed movement in substrate concentration gradient. Polystyrene microparticles were functionalized with the enzymes urease and catalase using a biotin-streptavidin linkage procedure. The motion of the enzyme-coated particles was studied in the presence of the respective substrates, using optical microscopy and dynamic light scattering analysis. The diffusion of the particles was found to increase in a substrate concentration dependent manner. The directed chemotactic movement of these enzyme-powered motors up the substrate gradient was studied using three-inlet microfluidic channel architecture.

Pregnant human peripheral leukocyte migration during several late pregnancy clinical conditions: a cross-sectional observational study.

PubMed

Takeda, Jun; Fang, Xin; Olson, David M

2017-01-10

Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating into stromal tissue. There they interact with resident immune and stromal cells to produce a mixture of matrix metalloproteinases, prostaglandins and cytokines including interleukin-1β (IL-1β) and IL-6 that in turn transform the uterus from pregnancy to parturition. Since migration is an early parturitional event our purpose was to study the migration of maternal peripheral blood leukocytes in response to a standard chemotactic signal during several different conditions of late pregnancy. We used a cross-sectional observational study design. Subjects were (sTL) spontaneous normal labour delivered vaginally at term, (TNL) elective caesarean section at term without labour, (PTL) preterm in labour, (PTNL) preterm not in labour, (TPTL) threatened preterm labour, and (pPROM) preterm with premature rupture of membranes. Leukocytes (100,000) obtained by venipuncture and chemotactic factor isolated from term labour fetal membranes were placed in the upper and lower halves, respectively, of a Boyden chamber separated by a filter with 3μm pores. Migrated leukocytes were assessed by flow cytometry. The number of leukocytes that migrated in 90 min was the primary outcome measure. Increased numbers of leukocytes from peripheral blood of women in labour (TL or PTL) or soon to go into labour (PPROM) migrated towards a chemotactic signal than did leukocytes from women not in labour (TNL, PTNL, or TPTL) (p < 0.0001). All pPROM delivered within 7d; TPTL delivered >30d. Receiver operating characteristic curve parameters indicated the cut-off point for delivery within 7d to be 37,082 leukocytes with sensitivity 78.1%, specificity 88.9%, positive predictive value 91.4%, negative predictive value 72.7%, and area under the curve 0.83. Leukocyte migration to a fetal membrane signal varies in a predictable fashion during various clinical situations of late gestation. This principle has the potential to be improved to become a clinical test to predict delivery.

Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

PubMed

Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

2014-04-11

Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

Synthetic chemerin-derived peptides suppress inflammation through ChemR23

PubMed Central

Cash, Jenna L.; Hart, Rosie; Russ, Andreas; Dixon, John P.C.; Colledge, William H.; Doran, Joanne; Hendrick, Alan G.; Carlton, Mark B.L.; Greaves, David R.

2008-01-01

Chemerin is a chemotactic protein that binds to the G protein–coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A140-A154), inhibited macrophage (MΦ) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MΦ chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23−/− mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23. PMID:18391062

Controlled Microfluidic Assembly and Functionalization of Complex Biomolecules

DTIC Science & Technology

2017-10-27

Name: The 15th International Conference on Micro and Nanotechnology for Power Generation and Energy Conversion Applications Conference Location...Paper or Presentation Conference Name: The 15th International Conference on Micro and Nanotechnology for Power Generation and Energy Conversion

Advances in Prosthetics and Orthotics

DTIC Science & Technology

2011-01-26

Teyhen, Granville) 2011 MHS Conference Limb-Socket Displacement 0 2 4 6 8 10 12 14 16 18 20 0-20 20-40 40-60 60-80 80-100 Percent Body Weight M i l l i m e...Strut AFO Ossur Cheetah Sprint foot 2011 MHS Conference Orthotic Functionality 19 - 2011 MHS Conference Orthotic Functionality  Hypothesis: Use of

The CatSper channel controls chemosensation in sea urchin sperm

PubMed Central

Seifert, Reinhard; Flick, Melanie; Bönigk, Wolfgang; Alvarez, Luis; Trötschel, Christian; Poetsch, Ansgar; Müller, Astrid; Goodwin, Normann; Pelzer, Patric; Kashikar, Nachiket D; Kremmer, Elisabeth; Jikeli, Jan; Timmermann, Bernd; Kuhl, Heiner; Fridman, Dmitry; Windler, Florian; Kaupp, U Benjamin; Strünker, Timo

2015-01-01

Sperm guidance is controlled by chemical and physical cues. In many species, Ca2+ bursts in the flagellum govern navigation to the egg. In Arbacia punctulata, a model system of sperm chemotaxis, a cGMP signaling pathway controls these Ca2+ bursts. The underlying Ca2+ channel and its mechanisms of activation are unknown. Here, we identify CatSper Ca2+ channels in the flagellum of A. punctulata sperm. We show that CatSper mediates the chemoattractant-evoked Ca2+ influx and controls chemotactic steering; a concomitant alkalization serves as a highly cooperative mechanism that enables CatSper to transduce periodic voltage changes into Ca2+ bursts. Our results reveal intriguing phylogenetic commonalities but also variations between marine invertebrates and mammals regarding the function and control of CatSper. The variations probably reflect functional and mechanistic adaptations that evolved during the transition from external to internal fertilization. PMID:25535245

Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function.

PubMed

Tuohy, J L; Lascelles, B D X; Griffith, E H; Fogle, J E

2016-07-01

Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA. That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses. Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs. Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018). Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

NASA Astrophysics Data System (ADS)

Minkoff, Marjorie Sue

A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the monoclonal antibody 2QD45 specifically immunoprecipitated the {rm M_ R} 67,000 ECF-binding protein from ^{125}{rm I}-labeled mouse, rat, and human eosinophils as assessed by SDS-PAGE and autoradiography. Two-dimensional gel electrophoresis showed that this ECF-binding protein has a lower PI point than either mouse or bovine albumin.

Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors

PubMed Central

1977-01-01

Polymorphonuclear leukocyte (PMN) chemotaxis has been examined under conditions which allow phase microscope observations of cells responding to controlled gradients of chemotactic factors. With this visual assay, PMNs can be seen to orient rapidly and reversibly to gradients of N-formylmethionyl peptides. The level of orientation depends upon the mean concentration of peptide present as well as the concentration gradient. The response allows an estimation of the binding constant of the peptide to the cell. In optimal gradients, PMNs can detect a 1% difference in the concentration of peptide. At high cell densities, PMNs incubated with active peptides orient their locomotion away from the center of the cell population. This orientation appears to be due to inactivation of the peptides by the cells. Such inactivation in vivo could help to limit an inflammatory response. PMID:264125

E. coli chemotaxis and super-diffusion

NASA Astrophysics Data System (ADS)

Dobnikar, Jure; Matthäus, Franziska; Jagodic, Marko

2010-03-01

The bacteria E. coli actively propel by switching between clockwise and anti-clockwise rotation of the flagella attached to their cell membranes. This results in two modes of motion: tumbling and swimming. The switching between the two modes is coupled to the ligand sensing through the chemotactic signalling pathway inside the cell. We modelled the signalling pathway and performed numerical simulations of the chemotactic motion of a large number of E. coli bacteria under various external conditions. We have shown that under certain conditions the thermal noise in the level of receptor-bound CheR (an enzyme responsible for methylation of the receptor sites) leads to super-diffusive behaviour (L'evy walk) which is advantageous for the bacterial populations in environments with scarce food. Exerting external pressure we might observe evolution of the wild-type to the super-diffusive populations.

Isolation of an N-acetyl-DL-phenylalanine beta-naphthyl esterase from rabbit peritoneal polymorphonuclear leukocytes.

PubMed

Tsung, P; Kegeles, S W; Showell, H J; Becker, E L

1975-09-22

An N-acetyl-DL-phenylalanine beta-naphthyl esterase has been purified 26-fold from rabbit peritoneal polymorphonuclear leukocytes. The purified enzyme was inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate. The apparent Km for hydrolysis of N-acetyl-DL-phenylalanine beta-naphthyl ester is 71 muM. Optimal reaction rates were observed at pH 6-8. No divalent cation requirement for the activation of the enzyme activity was observed. The esterase activity was neither inhibited nor stimulated by bacterial factor, complement component C5a, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) which are attractants or repellents for polymorphonuclear leukocytes. High chemotactic activity was observed in the partially purified fraction of the enzyme. The chemotactic activity, like the enzyme activity, was completely inhibited by 10(-7) M phosphonate.

Peptides as modifiers of Na+-induced pinocytosis in starved Amoeba proteus.

PubMed

Josefsson, J O; Johansson, P

1985-01-01

Low concentrations of six peptide hormones; glucagon, vasoactive intestinal peptide, substance P, angiotensin II, lysine-vasopressin, arginine-vasopressin, and the chemotactic peptide fMet-Leu-Phe, activated the capacity for pinocytosis in starved Amoeba proteus. Competitive inhibitors of the chemotactic peptide in leucocytes inhibited activation by fMet-Leu-Phe, suggesting that its action in the amoeba is mediated by specific receptors. The opioid peptides, beta-endorphin, dynorphin (1-13) and leu-enkephalin abolished through a naloxone-sensitive mechanism activation by hormones and several other activating agents. Also, low concentrations of beef and pork insulin inhibited activation by peptide hormones. An insulin analogue of low potency in mammalian cells was inactive in the amoeba. These results support the hypothesis that besides opioid receptors, there may be insulin receptors and possibly receptors for several other peptide hormones in Amoeba proteus.

Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.

PubMed

Tahtouh, Muriel; Croq, Françoise; Vizioli, Jacopo; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Daha, Mohamed R; Pestel, Joël; Lefebvre, Christophe

2009-02-01

In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.

Matrix Metalloproteinase-8 Facilitates Neutrophil Migration through the Corneal Stromal Matrix by Collagen Degradation and Production of the Chemotactic Peptide Pro-Gly-Pro

PubMed Central

Lin, Michelle; Jackson, Patricia; Tester, Angus M.; Diaconu, Eugenia; Overall, Christopher M.; Blalock, J. Edwin; Pearlman, Eric

2008-01-01

Matrix metalloproteinase (MMP)-8 and MMP-9 play several roles in inflammation, including degradation of extracellular matrix (ECM) components and regulation of cytokine activity. To determine the roles of MMP-8 and MMP-9 in a neutrophil-dependent inflammatory response, we used a murine model of corneal inflammation in which LPS is injected into the corneal stroma. In contrast to wild-type mice, we found that i) lipopolysaccharide (LPS)-injected CXCR2−/− corneas had impaired neutrophil infiltration and did not express either MMP-8 or MMP-9; ii) neutrophil migration through the central cornea was impaired in Mmp8−/−, but not Mmp9−/−, mice; iii) neutrophil migration was inhibited in collagenase-resistant mice; iv) the chemotactic Pro-Gly-Pro (PGP) tripeptide that binds CXCR2 was decreased in CXCR2−/− mice; v) PGP production was impaired in Mmp8−/− corneas; and vi) neutralizing anti-PGP antibody did not inhibit neutrophil infiltration in Mmp8−/− mice. We found no effects of MMP-8 on LPS-induced CXC chemokine (LIX, or CXCL5)-induced neutrophil recruitment or on LPS-induced CXC chemokine production. Together, these studies indicate that neutrophils contribute to the production of both MMP-8 and MMP-9 in LPS-injected corneas and that MMP-8 regulates neutrophil migration through the dense collagenous ECM of the corneal stroma by generating chemotactic PGP during inflammation. PMID:18556780

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury.

PubMed

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle; Summer, Ross

2014-01-01

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5'-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI.

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury

PubMed Central

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle

2013-01-01

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5′-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI. PMID:24285266

Many-body dynamics of chemically propelled nanomotors

NASA Astrophysics Data System (ADS)

Colberg, Peter H.; Kapral, Raymond

2017-08-01

The collective behavior of chemically propelled sphere-dimer motors made from linked catalytic and noncatalytic spheres in a quasi-two-dimensional confined geometry is studied using a coarse-grained microscopic dynamical model. Chemical reactions at the catalytic spheres that convert fuel to product generate forces that couple to solvent degrees of freedom as a consequence of momentum conservation in the microscopic dynamics. The collective behavior of the many-body system is influenced by direct intermolecular interactions among the motors, chemotactic effects due to chemical gradients, hydrodynamic coupling, and thermal noise. Segregation into high and low density phases and globally homogeneous states with strong fluctuations are investigated as functions of the motor characteristics. Factors contributing to this behavior are discussed in the context of active Brownian models.

Fine Tuning Cell Migration by a Disintegrin and Metalloproteinases

PubMed Central

Theodorou, K.

2017-01-01

Cell migration is an instrumental process involved in organ development, tissue homeostasis, and various physiological processes and also in numerous pathologies. Both basic cell migration and migration towards chemotactic stimulus consist of changes in cell polarity and cytoskeletal rearrangement, cell detachment from, invasion through, and reattachment to their neighboring cells, and numerous interactions with the extracellular matrix. The different steps of immune cell, tissue cell, or cancer cell migration are tightly coordinated in time and place by growth factors, cytokines/chemokines, adhesion molecules, and receptors for these ligands. This review describes how a disintegrin and metalloproteinases interfere with several steps of cell migration, either by proteolytic cleavage of such molecules or by functions independent of proteolytic activity. PMID:28260841

Monocyte function in infectious mononucleosis: evidence for a reversible cellular defect.

PubMed

Britton, S

1976-10-01

Migration of blood monocytes from patients with acute infectious mononucleosis and from normal controls was measured against chemotactic factors in serum. Moncytes from patients with acute infectious mononucleosis showed decreased migration as compared with that of control monocytes. However, serum from patients with infectious mononucleosis contained normal or above normal amounts of chemotaxins for monocytes. The migratory defect of monocytes from patients with infectious mononucleosis was reversible within three months after the onset of diesease. The cause of this monocyte migration defect in infectious mononucleosis is though to be an in vivo blockade of receptors on monocytes for chemotaxins, and it is speculated that this defect can partially explain the explain the ablated delayed-hypersensitivity skin reactions in this disease.

The Press Conferences of Eleanor Roosevelt.

ERIC Educational Resources Information Center

Beasley, Maurine H.

Newly discovered transcriptions of 87 of First Lady Eleanor Roosevelt's women-only press conferences held from 1933 to 1945 make possible an examination of the objectives, topics, and value of these conferences. By holding the conferences, Mrs. Roosevelt attributed to women an important function in the political communication process, and at the…

Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides

PubMed Central

Bisht, Sandeep; Pandey, Piyush; Sood, Anchal; Sharma, Shivesh; Bisht, N. S.

2010-01-01

Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K) of isolates were found to increase with successive increase in substrate concentration (0.5 to 1.0 mg/50ml). B. circulans SBA12 and Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B. circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of naphthalene respectively after 6 days of incubation as determined by HPLC analysis. PMID:24031572

THE REGULATORY ROLE OF DIVALENT CATIONS IN HUMAN GRANULOCYTE CHEMOTAXIS

PubMed Central

Gallin, John I.; Rosenthal, Alan S.

1974-01-01

Optimal human granulocyte chemotaxis has been shown to require both calcium and magnesium. Exposure of granulocytes to three different chemotactic factors (C5a, kallikrein, and dialyzable transfer factor) yielded a rapid calcium release, depressed calcium uptake, and was associated with a shift of calcium out of the cytoplasm and into a granule fraction. Colchicine, sodium azide, and cytochalasin B, in concentrations that inhibited chemotaxis, also inhibited calcium release while low concentrations of cytochalasin B, which enhanced chemotaxis, also enhanced calcium release. Microtubule assembly was visualized both in cells suspended in C5a without a chemotactic gradient and in cells actively migrating through a Micropore filter. The data suggest microtubule assembly is regulated, at least, in part, by the level of cytoplasmic calcium. It is proposed that asymmetric assembly of microtubules may be instrumental in imparting the net vector of motion during chemotaxis. PMID:4855032

Modelling the collective response of heterogeneous cell populations to stationary gradients and chemical signal relay

NASA Astrophysics Data System (ADS)

Pineda, M.; Eftimie, R.

2017-12-01

The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement of heterogeneous subpopulations of chemically interacting cells towards an imposed stable chemical gradient. Our simulations show explicitly how self-organisation of cell populations (which could lead to engulfment or complete cell segregation) can arise from the heterogeneity of chemotactic responses alone. This new result complements current theoretical and experimental studies that emphasise the role of differential cell-cell adhesion on self-organisation and spatial structure of cellular aggregates. We also investigate how the speed of individual cell aggregations increases with the chemotactic sensitivity of the cells, and decreases with the number of cells inside the aggregates

Termitarium-Inhabiting Bacillus spp. Enhanced Plant Growth and Bioactive Component in Turmeric (Curcuma longa L.).

PubMed

Chauhan, Ankit Kumar; Maheshwari, Dinesh Kumar; Dheeman, Shrivardhan; Bajpai, Vivek K

2017-02-01

Curcumin (diferuloyl methane) is the main bioactive component of turmeric (Curcuma longa L.) having remarkable multipotent medicinal and therapeutic applications. Two Bacilli isolated from termitarium soil and identified as Bacillus endophyticus TSH42 and Bacillus cereus TSH77 were used for bacterization of rhizome for raising C. longa ver. suguna for growth and enhancement. Both the strains showed remarkable PGP activities and also chemotactic in nature with high chemotactic index. Turmeric plants bacterized with strains B. endophyticus TSH42 and B. cereus TSH77 individually and in combination increased plant growth and turmeric production up to 18% in field trial in comparison to non-bacterized plants. High-performance liquid chromatography analysis was performed to determine the content of curcumin, which showed concentration of curcumin in un-inoculated turmeric as 3.66 g which increased by 13.6% (4.16 g) when combination of TSH42 and TSH77 was used.

[Inhibition of monocytes adhesion to the intima of arterial wall by local expression of antisense monocyte chemotactic protein-1].

PubMed

Wu, Q; Qiao, H; Wang, Z; Zhang, H; Liu, P; Xu, M; Ren, G; Zhao, S; She, M

2000-04-01

To study the mechanism of monocyte recruitment in atherogenesis and to clarify the effect of monocyte chemotactic protein-1 (MCP-1) in this process. Femoral arteries isolated from the rabbits which had been fed with a high cholesterol diet and locally perfused with MM-LDL within the artery beforehand, were used as the models. Antisense MCP-1cDNA was transferred into the arterial wall by injecting recombinant LNCX-anti-MCP-1/liposomal complex in the femoral sheath and the periarterial tissue. Expression of antisense MCP-1 mediated by recombinant LNCX plasmid/lipsomal complex gene transfer enabled to inhibit MCP-1 gene expression and adhesion of monocyte to the intima. MCP-1 plays an important role on the recruitment of monocytes in the arterial wall, which provides a potential clue in developing a gene therapy project for the prevention and treatment of atherogenesis.

Effect of conglutinin on phagocytic activity of bovine granulocytes.

PubMed

Dec, M; Wernicki, A; Puchalski, A; Urban-Chmiel, R; Radej, S

2012-01-01

In the present study we investigated the effect of bovine conglutinin on the phagocytic activity of leukocytes. We measured both the chemotactic activity of conglutinin and its effect on the internalization of zymosan particles and E. coli by granulocytes. We also assessed the binding of conglutinin to various microorganisms isolated from clinical cases in cattle. We showed that conglutinin binds strongly to the surface of yeast cells and to mannan-rich zymosan particles, while weak binding was observed in the case of the bacterial strains tested, including those whose O antigen is composed of mannan. Conglutinin (1-10 microg/ml) neither acts as a chemotactic factor for peripheral blood leukocytes nor affects ingestion of E. coli by granulocytes. However, as flow cytometry based assay showed, conglutinin (0.1-1 microg/ml) increased ingestion of zymosan expressed as mean fluorescence intensity (MFI) of positive cells.

PREFACE: Progress in Nonequilibrium Green's Functions V (PNGF V)

NASA Astrophysics Data System (ADS)

van Leeuwen, Robert; Tuovinen, Riku; Bonitz, Michael

2013-03-01

(The PDF contains: an obituary and in memoriam for David C. Langreth, a list of the conference participants, a complete list of the conference talks and posters and several photographs taken during the conference. ) The fifth interdisciplinary conference 'Progress in Nonequilibrium Green's Functions' (PNGF5) was held at the University of Jyväskylä, Finland, on 27--31 August 2012. The conference continued the successful tradition of its predecessors (Rostock 1999, Dresden 2002, Kiel 2005 and Glasgow 2009) to bring together different communities for an interdisciplinary exchange of recent results and theoretical concepts. The conference focused on recent developments, current challenges and future perspectives in nonequilibrium Green's functions theory in various fields of physics but included also other many-body methods. Roughly 20 invited talks were given by some of the top scientists in the field, accompanied by 10 contributed talks. (Slides of several presentations can be found online at www.jyu.fi/physics/pngf5.) Also a poster session was set up to enhance scientific discussions, building up new collaborations and enriching views and ideas. As at the previous meetings, the atmosphere was interactive and stimulating, benefitting both experienced scientists and young researchers and students. The present volume contains 14 articles based on works presented at this conference. The articles partly have review character so they should be of use for an interdisciplinary community working or interested in nonequilibrium Green's functions. All papers were refereed according to high scientific standards. The conference would not have been possible without financial support from the Federation of Finnish Learned Societies, Finnish Academy of Science and Letters and Nanoscience Center of the university of Jyväskylä which are greatly acknowledged. The local organizing committee is also grateful to the administration personnel, Marjut Hilska and Riitta-Liisa Kuittinen, for assistance. We further thank professor Antti-Pekka Jauho for invaluable help and advice during the organization of the conference. The editors of the present conference proceedings acknowledge the authors for their excellent papers and all the referees for participating in a thorough peer-reviewing of the manuscripts. Finally, it is our pleasure to announce that the sixth conference 'Progress in Nonequilibrium Green's Functions' (PNGF6) will be held in August 2015 at the University of Lund, Sweden. Riku Tuovinen and Robert van Leeuwen University of Jyväskylä Michael Bonitz University of Kiel February 2013

Functional Capacity Evaluation Research: Report from the Second International Functional Capacity Evaluation Research Meeting.

PubMed

James, C L; Reneman, M F; Gross, D P

2016-03-01

Functional capacity evaluations are an important component of many occupational rehabilitation programs and can play a role in facilitating reintegration to work thus improving health and disability outcomes. The field of functional capacity evaluation (FCE) research has continued to develop over recent years, with growing evidence on the reliability, validity and clinical utility of FCE within different patient and healthy worker groups. The second International FCE Research Conference was held in Toronto, Canada on October 2nd 2014 adjacent to the 2014 Work Disability Prevention Integration conference. This paper describes the outcomes of the conference. Fifty-four participants from nine countries attended the conference where eleven research projects and three workshops were presented. The conference provided an opportunity to discuss FCE practice, present new research and provide a forum for discourse around the issues pertinent to FCE use. Conference presentations covered aspects of FCE use including the ICF-FCE interface, aspects of reliability and validity, consideration of specific injury populations, comparisons of FCE components and a lively debate on the merits of 'Man versus Machine' in FCE's. Researchers, clinicians, and other professionals in the FCE area have a common desire to improve the content and quality of FCE research and to collaborate to further develop research across systems, cultures and countries.

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

PubMed Central

Sánchez, Jon Andoni; Alfonso, Amparo; Rodriguez, Ines; Alonso, Eva; Cifuentes, José Manuel; Bermudez, Roberto; Rateb, Mostafa E.; Jaspars, Marcel; Houssen, Wael E.; Ebel, Rainer; Tabudravu, Jioji; Botana, Luís M.

2016-01-01

The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds. PMID:27822214

Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation.

PubMed

Sánchez, Jon Andoni; Alfonso, Amparo; Rodriguez, Ines; Alonso, Eva; Cifuentes, José Manuel; Bermudez, Roberto; Rateb, Mostafa E; Jaspars, Marcel; Houssen, Wael E; Ebel, Rainer; Tabudravu, Jioji; Botana, Luís M

2016-01-01

The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds.

Chemotactic preferences govern competition and pattern formation in simulated two-strain microbial communities.

PubMed

Centler, Florian; Thullner, Martin

2015-01-01

Substrate competition is a common mode of microbial interaction in natural environments. While growth properties play an important and well-studied role in competition, we here focus on the influence of motility. In a simulated two-strain community populating a homogeneous two-dimensional environment, strains competed for a common substrate and only differed in their chemotactic preference, either responding more sensitively to a chemoattractant excreted by themselves or responding more sensitively to substrate. Starting from homogeneous distributions, three possible behaviors were observed depending on the competitors' chemotactic preferences: (i) distributions remained homogeneous, (ii) patterns formed but dissolved at a later time point, resulting in a shifted community composition, and (iii) patterns emerged and led to the extinction of one strain. When patterns formed, the more aggregating strain populated the core of microbial aggregates where starving conditions prevailed, while the less aggregating strain populated the more productive zones at the fringe or outside aggregates, leading to a competitive advantage of the less aggregating strain. The presence of a competitor was found to modulate a strain's behavior, either suppressing or promoting aggregate formation. This observation provides a potential mechanism by which an aggregated lifestyle might evolve even if it is initially disadvantageous. Adverse effects can be avoided as a competitor hinders aggregate formation by a strain which has just acquired this ability. The presented results highlight both, the importance of microbial motility for competition and pattern formation, and the importance of the temporal evolution, or history, of microbial communities when trying to explain an observed distribution.

A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrophil chemotaxis and the memory effect.

PubMed

Yang, Ke; Wu, Jiandong; Xu, Guoqing; Xie, Dongxue; Peretz-Soroka, Hagit; Santos, Susy; Alexander, Murray; Zhu, Ling; Zhang, Michael; Liu, Yong; Lin, Francis

2017-04-18

Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health sciences. Neutrophils are a widely used model to study eukaryotic cell migration and neutrophil chemotaxis itself can lead to protective or harmful immune actions to the body. While much has been learnt from past research about how neutrophils effectively navigate through a chemoattractant gradient, many interesting questions remain unclear. For example, while it is tempting to model neutrophil chemotaxis using the well-established biased random walk theory, the experimental proof was challenged by the cell's highly persistent migrating nature. A special experimental design is required to test the key predictions from the random walk model. Another question that has interested the cell migration community for decades concerns the existence of chemotactic memory and its underlying mechanism. Although chemotactic memory has been suggested in various studies, a clear quantitative experimental demonstration will improve our understanding of the migratory memory effect. Motivated by these questions, we developed a microfluidic cell migration assay (so-called dual-docking chip or D 2 -Chip) that can test both the biased random walk model and the memory effect for neutrophil chemotaxis on a single chip enabled by multi-region gradient generation and dual-region cell alignment. Our results provide experimental support for the biased random walk model and chemotactic memory for neutrophil chemotaxis. Quantitative data analyses provide new insights into neutrophil chemotaxis and memory by making connections to entropic disorder, cell morphology and oscillating migratory response.

Chemotactic Cues for NOTCH1-Dependent Leukemia

PubMed Central

Piovan, Erich; Tosello, Valeria; Amadori, Alberto; Zanovello, Paola

2018-01-01

The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL. Leukemia patients often present with high-blood cell counts, diffuse disease with infiltration of the bone marrow, secondary lymphoid organs, and diffusion to the central nervous system (CNS). Chemokines are chemotactic cytokines that regulate migration of cells between tissues and the positioning and interactions of cells within tissue. Homeostatic chemokines and their receptors have been implicated in regulating organ-specific infiltration, but may also directly and indirectly modulate tumor growth. Recently, oncogenic NOTCH1 has been shown to regulate infiltration of leukemic cells into the CNS hijacking the CC-chemokine ligand 19/CC-chemokine receptor 7 chemokine axis. In addition, a crucial role for the homing receptor axis CXC-chemokine ligand 12/CXC-chemokine receptor 4 has been demonstrated in leukemia maintenance and progression. Moreover, the CCL25/CCR9 axis has been implicated in the homing of leukemic cells into the gut, particularly in the presence of phosphatase and tensin homolog tumor suppressor loss. In this review, we summarize the latest developments regarding the role of NOTCH signaling in regulating the chemotactic microenvironmental cues involved in the generation and progression of T-ALL and compare these findings to B-CLL. PMID:29666622

The importance of interleukin-8 as a neutrophil chemoattractant in the lungs of cattle with pneumonic pasteurellosis.

PubMed Central

Caswell, J L; Middleton, D M; Gordon, J R

2001-01-01

Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8-neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions. PMID:11768129

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

USGS Publications Warehouse

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.

Chemotaxis by natural populations of coral reef bacteria.

PubMed

Tout, Jessica; Jeffries, Thomas C; Petrou, Katherina; Tyson, Gene W; Webster, Nicole S; Garren, Melissa; Stocker, Roman; Ralph, Peter J; Seymour, Justin R

2015-08-01

Corals experience intimate associations with distinct populations of marine microorganisms, but the microbial behaviours underpinning these relationships are poorly understood. There is evidence that chemotaxis is pivotal to the infection process of corals by pathogenic bacteria, but this evidence is limited to experiments using cultured isolates under laboratory conditions. We measured the chemotactic capabilities of natural populations of coral-associated bacteria towards chemicals released by corals and their symbionts, including amino acids, carbohydrates, ammonium and dimethylsulfoniopropionate (DMSP). Laboratory experiments, using a modified capillary assay, and in situ measurements, using a novel microfabricated in situ chemotaxis assay, were employed to quantify the chemotactic responses of natural microbial assemblages on the Great Barrier Reef. Both approaches showed that bacteria associated with the surface of the coral species Pocillopora damicornis and Acropora aspera exhibited significant levels of chemotaxis, particularly towards DMSP and amino acids, and that these levels of chemotaxis were significantly higher than that of bacteria inhabiting nearby, non-coral-associated waters. This pattern was supported by a significantly higher abundance of chemotaxis and motility genes in metagenomes within coral-associated water types. The phylogenetic composition of the coral-associated chemotactic microorganisms, determined using 16S rRNA amplicon pyrosequencing, differed from the community in the seawater surrounding the coral and comprised known coral associates, including potentially pathogenic Vibrio species. These findings indicate that motility and chemotaxis are prevalent phenotypes among coral-associated bacteria, and we propose that chemotaxis has an important role in the establishment and maintenance of specific coral-microbe associations, which may ultimately influence the health and stability of the coral holobiont.

Role of Chemotaxis in the Ecology of Denitrifiers

PubMed Central

Kennedy, Michael J.; Lawless, James G.

1985-01-01

A modification of the Adler capillary assay was used to evaluate the chemotactic responses of several denitrifiers to nitrate and nitrite. Strong positive chemotaxis was observed to NO3− and NO2− by soil isolates of Pseudomonas aeruginosa, Pseudomonas fluorescens, and Pseudomonas stutzeri, with the peak response occurring at 10−3 M for both attractants. In addition, a strong chemoattraction to serine (peak response at 10−2 M), tryptone, and a soil extract, but not to NH4+, was observed for all denitrifiers tested. Chemotaxis was not dependent on a previous growth on NO3−, NO2−, or a soil extract, and the chemoattraction to NO3− occurred when the bacteria were grown aerobically or anaerobically. However, the best response to NO3− was usually observed when the cells were grown aerobically with 10 mM NO3− in the growth medium. Capillary tubes containing 10−3 M NO3− submerged into soil-water mixtures elicited a significant chemotactic response to NO3− by the indigenous soil microflora, the majority of which were Pseudomonas spp. A chemotactic strain of P. fluorescens also was shown to survive significantly better in aerobic and anaerobic soils than was a nonmotile strain of the same species. Both strains had equal growth rates in liquid cultures. Thus, chemotaxis may be one mechanism by which denitrifiers successfully compete for available NO3− and NO2−, and which may facilitate the survival of naturally occurring populations of some denitrifiers. PMID:16346690

Delayed brain ischemia tolerance induced by electroacupuncture pretreatment is mediated via MCP-induced protein 1

PubMed Central

2013-01-01

Background Emerging studies have demonstrated that pretreatment with electroacupuncture (EA) induces significant tolerance to focal cerebral ischemia. The present study seeks to determine the involvement of monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified novel modulator of inflammatory reactions, in the cerebral neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of EA pretreatment-induced ischemic brain tolerance. Methods Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 minutes in male C57BL/6 mice and MCPIP1 knockout mice. Transcription and expression of MCPIP1 gene was monitored by qRT-PCR, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, proinflammatory cytokines and leukocyte infiltration in brain and NF-κB signaling were evaluated after ischemia/reperfusion. Results MCPIP1 protein and mRNA levels significantly increased specifically in mouse brain undergoing EA pretreatment. EA pretreatment significantly attenuated the infarct volume, neurological deficits, upregulation of proinflammatory cytokines and leukocyte infiltration in the brain of wild-type mice after MCAO compared with that of the non-EA group. MCPIP1-deficient mice failed to evoke EA pretreatment-induced tolerance compared with that of the control MCPIP1 knockout group without EA treatment. Furthermore, the activation of NF-κB signaling was significantly reduced in EA-pretreated wild-type mice after MCAO compared to that of the non-EA control group and MCPIP1-deficient mice failed to confer the EA pretreatment-induced inhibition of NF-κB signaling after MCAO. Conclusions Our data demonstrated that MCPIP1 deficiency caused significant lack of EA pretreatment-induced cerebral protective effects after MCAO compared with the control group and that MCPIP1 is involved in EA pretreatment-induced delayed brain ischemia tolerance. PMID:23663236

Dendritic Cell Migration Toward CCL21 Gradient Requires Functional Cx43

PubMed Central

Ruez, Richard; Dubrot, Juan; Zoso, Alice; Bacchetta, Marc; Molica, Filippo; Hugues, Stéphanie; Kwak, Brenda R.; Chanson, Marc

2018-01-01

Dendritic cells (DCs) travel through lymphatic vessels to transport antigens and present them to T cells in lymph nodes. DCs move directionally toward lymphatics by virtue of their CCR7 and a CCL21 chemotactic gradient. We evaluated in vivo and in bone marrow-derived dendritic cells (BMDCs) whether the gap junction protein Cx43 contributes to CCL21/CCR7-dependent DC migration in wild-type (WT) mice, heterozygous (Cx43+/−) mice and mice expressing a truncated form of Cx43 lacking its regulatory C-terminus (Cx43K258/−). In a model of flank skin inflammation, we found that the recruitment of myeloid DCs (mDCs) to skin draining lymph nodes was reduced in Cx43K258/− mice as compared to WT and Cx43+/− mice. In addition, the migration of Cx43K258/− BMDCs toward CCL21 was abolished in an in vitro chemotactic assay while it was only reduced in Cx43+/− cells. Both mutant genotypes showed defects in the directionality of BMDC migration as compared to WT BMDCs. No difference was found between the three populations of BMDCs in terms of expression of surface markers (CD11c, CD86, CD80, CD40, MHC-II, and CCR7) after differentiation and TLR activation. Finally, examination of the CCR7-induced signaling pathways in BMDCs revealed normal receptor-induced mobilization of intracellular Ca2+. These results demonstrate that full expression of an intact Cx43 is critical to the directionality and rate of DC migration, which may be amenable to regulation of the immune response. PMID:29636699

The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion.

PubMed

Koenen, Andrea; Babendreyer, Aaron; Schumacher, Julian; Pasqualon, Tobias; Schwarz, Nicole; Seifert, Anke; Deupi, Xavier; Ludwig, Andreas; Dreymueller, Daniela

2017-01-01

The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling. In this work, modeling analyses revealed that the phenylalanine F3.51 in CXCR6 might have impact on intramolecular interactions including hydrogen bonds by this possibly changing receptor function. Initial investigations with embryonic kidney HEK293 cells and further studies with monocytic THP-1 cells showed that mutation of DRF into DRY does not influence ligand binding, receptor internalization, receptor recycling, and protein kinase B (AKT) signaling. Adhesion was slightly decreased in a time-dependent manner. However, CXCL16-induced calcium signaling and migration were increased. Vice versa, when the DRY motif of the related receptor CX3CR1 was mutated into DRF the migratory response towards CX3CL1 was diminished, indicating that the presence of a DRF motif generally impairs chemotaxis in chemokine receptors. Transmembrane and soluble CXCL16 play divergent roles in homeostasis, inflammation, and cancer, which can be beneficial or detrimental. Therefore, the DRF motif of CXCR6 may display a receptor adaptation allowing adhesion and cell retention by transmembrane CXCL16 but reducing the chemotactic response to soluble CXCL16. This adaptation may avoid permanent or uncontrolled recruitment of inflammatory cells as well as cancer metastasis.

The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion

PubMed Central

Koenen, Andrea; Babendreyer, Aaron; Schumacher, Julian; Pasqualon, Tobias; Schwarz, Nicole; Seifert, Anke; Deupi, Xavier

2017-01-01

The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling. In this work, modeling analyses revealed that the phenylalanine F3.51 in CXCR6 might have impact on intramolecular interactions including hydrogen bonds by this possibly changing receptor function. Initial investigations with embryonic kidney HEK293 cells and further studies with monocytic THP-1 cells showed that mutation of DRF into DRY does not influence ligand binding, receptor internalization, receptor recycling, and protein kinase B (AKT) signaling. Adhesion was slightly decreased in a time-dependent manner. However, CXCL16-induced calcium signaling and migration were increased. Vice versa, when the DRY motif of the related receptor CX3CR1 was mutated into DRF the migratory response towards CX3CL1 was diminished, indicating that the presence of a DRF motif generally impairs chemotaxis in chemokine receptors. Transmembrane and soluble CXCL16 play divergent roles in homeostasis, inflammation, and cancer, which can be beneficial or detrimental. Therefore, the DRF motif of CXCR6 may display a receptor adaptation allowing adhesion and cell retention by transmembrane CXCL16 but reducing the chemotactic response to soluble CXCL16. This adaptation may avoid permanent or uncontrolled recruitment of inflammatory cells as well as cancer metastasis. PMID:28267793

Chemometric analysis of Hymenoptera toxins and defensins: A model for predicting the biological activity of novel peptides from venoms and hemolymph.

PubMed

Saidemberg, Daniel M; Baptista-Saidemberg, Nicoli B; Palma, Mario S

2011-09-01

When searching for prospective novel peptides, it is difficult to determine the biological activity of a peptide based only on its sequence. The "trial and error" approach is generally laborious, expensive and time consuming due to the large number of different experimental setups required to cover a reasonable number of biological assays. To simulate a virtual model for Hymenoptera insects, 166 peptides were selected from the venoms and hemolymphs of wasps, bees and ants and applied to a mathematical model of multivariate analysis, with nine different chemometric components: GRAVY, aliphaticity index, number of disulfide bonds, total residues, net charge, pI value, Boman index, percentage of alpha helix, and flexibility prediction. Principal component analysis (PCA) with non-linear iterative projections by alternating least-squares (NIPALS) algorithm was performed, without including any information about the biological activity of the peptides. This analysis permitted the grouping of peptides in a way that strongly correlated to the biological function of the peptides. Six different groupings were observed, which seemed to correspond to the following groups: chemotactic peptides, mastoparans, tachykinins, kinins, antibiotic peptides, and a group of long peptides with one or two disulfide bonds and with biological activities that are not yet clearly defined. The partial overlap between the mastoparans group and the chemotactic peptides, tachykinins, kinins and antibiotic peptides in the PCA score plot may be used to explain the frequent reports in the literature about the multifunctionality of some of these peptides. The mathematical model used in the present investigation can be used to predict the biological activities of novel peptides in this system, and it may also be easily applied to other biological systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Diffusion in the presence of a local attracting factor: Theory and interdisciplinary applications.

PubMed

Veermäe, Hardi; Patriarca, Marco

2017-06-01

In many complex diffusion processes the drift of random walkers is not caused by an external force, as in the case of Brownian motion, but by local variations of fitness perceived by the random walkers. In this paper, a simple but general framework is presented that describes such a type of random motion and may be of relevance in different problems, such as opinion dynamics, cultural spreading, and animal movement. To this aim, we study the problem of a random walker in d dimensions moving in the presence of a local heterogeneous attracting factor expressed in terms of an assigned position-dependent "attractiveness function." At variance with standard Brownian motion, the attractiveness function introduced here regulates both the advection and diffusion of the random walker, thus providing testable predictions for a specific form of fluctuation-relations. We discuss the relation between the drift-diffusion equation based on the attractiveness function and that describing standard Brownian motion, and we provide some explicit examples illustrating its relevance in different fields, such as animal movement, chemotactic diffusion, and social dynamics.

Effects of Simulated Microgravity on Functions of Neutrophil-like HL-60 Cells

NASA Astrophysics Data System (ADS)

Wang, Chengzhi; Li, Ning; Zhang, Chen; Sun, Shujin; Gao, Yuxin; Long, Mian

2015-11-01

Altered gravity, especially microgravity affects cellular functions of immune cells and can result in immune dysfunction for long-term, manned spaceflight and space exploration. The underlying mechanism, however, of sensing and responding to the gravity alteration is poorly understood. Here, a rotary cell culture system (RCCS) bioreactor was used to elucidate the effects of simulated microgravity on polymorphonuclear neutrophils (PMN)-like HL-60 cells. Alteration of cell morphology, up-regulation of (nitric oxide) NO production, enhancement of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein 1 (MCP-1) secretion, and diversity of cellular adhesion molecule expression were observed for the cells cultured in RCCS, leading to the up-regulated inflammatory immune responses and host defense. It was also indicated that such alterations in biological responses of PMNs mediated the reduced rolling velocity and decreased adhesion of PMN-like HL-60 cells on endothelial cells under shear flow. This work furthers the understandings in the effects and mechanism of microgravity on PMN functions, which are potentially helpful for optimizing the countermeasures to immune suppression in the future long-term, manned spaceflight.

Diffusion in the presence of a local attracting factor: Theory and interdisciplinary applications

NASA Astrophysics Data System (ADS)

Veermäe, Hardi; Patriarca, Marco

2017-06-01

In many complex diffusion processes the drift of random walkers is not caused by an external force, as in the case of Brownian motion, but by local variations of fitness perceived by the random walkers. In this paper, a simple but general framework is presented that describes such a type of random motion and may be of relevance in different problems, such as opinion dynamics, cultural spreading, and animal movement. To this aim, we study the problem of a random walker in d dimensions moving in the presence of a local heterogeneous attracting factor expressed in terms of an assigned position-dependent "attractiveness function." At variance with standard Brownian motion, the attractiveness function introduced here regulates both the advection and diffusion of the random walker, thus providing testable predictions for a specific form of fluctuation-relations. We discuss the relation between the drift-diffusion equation based on the attractiveness function and that describing standard Brownian motion, and we provide some explicit examples illustrating its relevance in different fields, such as animal movement, chemotactic diffusion, and social dynamics.

Comparison of colony stimulation factors on in vitro rat and human neutrophil function.

PubMed

Wheeler, J G; Huffine, M E; Childress, S; Sikes, J

1994-01-01

The effects of rhCSFs on in vitro polymorphonuclear leukocyte (PMN) function were studied in Sprague-Dawley neonatal and adult rats and adult and umbilical cord derived human PMN to compare species response. Following in vitro exposure to buffer or rhCSFs (50-100 micrograms/ml), PMN oxidative burst, chemotactic activity and adherence protein expression were measured. RhG-CSF increased the oxidative burst of adult rat PMN as measured by chemiluminescence and altered CD11b/CD18 in resting neonatal rat but not adult rat cells. RhGM-CSF had no effect on adult rat PMN function in vitro, but led to modest changes in adult rat PMN diapedesis across rat peritoneum. No responses were noted to rhM-CSF. Human PMN responded best to GM-CSF (particularly in the neonate), intermediately to G-CSF and none to M-CSF. These experiments show that the profile of cytokine effects is not similar in adult and neonatal rat PMN when compared to human cells. The diversity of actions in other species must be considered when using rhCSFs in animal models.

Harnessing the power of macrophages/monocytes for enhanced bone tissue engineering.

PubMed

Dong, Lei; Wang, Chunming

2013-06-01

Bone tissue engineering has attracted considerable attention as a promising treatment modality for severe bone degeneration. The pressing need for more sophisticated and fully functional bone substitutes has spurred a refocus on the development of bone constructs in a way more comparable to the physiological process. Current research is increasingly revealing the central roles of macrophages/monocytes in regulating bone development and repair, so we propose that these immunocytes can play a similar pivotal role in directing engineered bone regeneration. Accordingly, we discuss two possible strategies to exemplify how the distinctive power of macrophages/monocytes--particularly their cytokine-secretion ability and chemotactic response to foreign materials--can be harnessed to enhance the performance of bone tissue engineering applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

76 FR 76867 - Delegation of Certain Function and Authority Conferred Upon the President by Section 1535(c)(1...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

..., Public Law 111-383, to make the specified report to the Committees on Armed Services, Foreign Relations...--Delegation of Certain Function and Authority Conferred Upon the President by Section 1535 (c)(1) of the Ike...

Meeting Our Users where They Conference: A Texas A&M Model to Support Librarian Attendance at Subject-Specific Conferences

ERIC Educational Resources Information Center

Hankins, Rebecca; Melgoza, Pauline; Seeger, Christina; Wan, Gary

2009-01-01

Today's academic librarian is frequently called upon to function as a subject specialist, with or without advanced degrees in other disciplines. One method of monitoring trends within a given field is to study its literature; another is to attend conferences in the discipline. Discipline-specific conference attendance by academic librarians…

CXCR6-CXCL16 interaction in the pathogenesis of Juvenile Idiopathic Arthritis.

PubMed

Martini, Giorgia; Cabrelle, Anna; Calabrese, Fiorella; Carraro, Samuela; Scquizzato, Elisa; Teramo, Antonella; Facco, Monica; Zulian, Francesco; Agostini, Carlo

2008-11-01

In order to evaluate the role of CXCR6/CXCL16 in driving lymphocyte migration into inflamed joints of children with oligoarticular Juvenile Idiopathic Arthritis (JIA) we analysed CXCR6 expression and functional capability in lymphocytes from synovial fluid (SF) by flow cytometry, by real-time polymerase chain reaction (RT-PCR) and migration assays. Furthermore, CXCR6 and CXCL16 expression in synovial tissue (ST) was analysed by immunohistochemistry. T cells isolated from SF of patients with JIA expressed CXCR6 which was functionally active as shown by chemotactic assays. The same cells expressed CXCR3 and it exerted a migratory activity in response to CXCL10. CXCL16 and CXCR6 were intensively expressed on the synovium cells, respectively on macrophages, synoviocytes and endothelial cells and on lymphocytes, synoviocytes and endothelial cells. Taken together, these data suggest that CXCR6 and CXCR3 act coordinately with respective ligands and are involved in the pathophysiology of JIA-associated inflammatory processes.

Chemokine Function in Periodontal Disease and Oral Cavity Cancer

PubMed Central

Sahingur, Sinem Esra; Yeudall, W. Andrew

2015-01-01

The chemotactic cytokines, or chemokines, comprise a superfamily of polypeptides with a wide range of activities that include recruitment of immune cells to sites of infection and inflammation, as well as stimulation of cell proliferation. As such, they function as antimicrobial molecules and play a central role in host defenses against pathogen challenge. However, their ability to recruit leukocytes and potentiate or prolong the inflammatory response may have profound implications for the progression of oral diseases such as chronic periodontitis, where tissue destruction may be widespread. Moreover, it is increasingly recognized that chronic inflammation is a key component of tumor progression. Interaction between cancer cells and their microenvironment is mediated in large part by secreted factors such as chemokines, and serves to enhance the malignant phenotype in oral and other cancers. In this article, we will outline the biological and biochemical mechanisms of chemokine action in host–microbiome interactions in periodontal disease and in oral cancer, and how these may overlap and contribute to pathogenesis. PMID:25999952

DECREASED HEART RATE IS ASSOCIATED WITH CARBAMATE-INDUCED ACTIVATION OF PRO-INFLAMMATORY SERUM PROTEINS.

EPA Science Inventory

Previously we reported that chlorpyrifos (CHP), an irreversible cholinesterase (ChE) inhibitor, induces hypertension in rats. Concomitant with hypertension, we found an increase in C-reactive protein, macrophage inflammatory protein-2 , monocyte chemotactic protein-5 and interfer...

3 CFR - Delegation of Certain Function and Authority Conferred Upon the President by Section 1535(c)(1...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 3 The President 1 2012-01-01 2012-01-01 false Delegation of Certain Function and Authority Conferred Upon the President by Section 1535(c)(1) of the Ike Skelton National Defense Authorization Act for Fiscal Year 2011 Presidential Documents Other Presidential Documents Memorandum of July 19, 2011 Delegation of Certain Function and Authority...

Processing of natural and recombinant CXCR3-targeting chemokines and implications for biological activity.

PubMed

Hensbergen, P J; van der Raaij-Helmer, E M; Dijkman, R; van der Schors, R C; Werner-Felmayer, G; Boorsma, D M; Scheper, R J; Willemze, R; Tensen, C P

2001-09-01

Chemokines comprise a class of peptides with chemotactic activity towards leukocytes. The potency of different chemokines for the same receptor often varies as a result of differences in primary structure. In addition, post-translational modifications have been shown to affect the effectiveness of chemokines. Although in several studies, natural CXCR3-targeting chemokines have been isolated, detailed information about the proteins and their possible modifications is lacking. Using a combination of liquid chromatography and mass spectrometry we studied the protein profile of CXCR3-targeting chemokines expressed by interferon-gamma-stimulated human keratinocytes. The biological implications of one of the identified modifications was studied in more detail using calcium mobilization and chemotaxis assays. We found that the primary structure of human CXCL10 is different from the generally accepted sequence. In addition we identified a C-terminally truncated CXCL10, lacking the last four amino acids. Native CXCL11 was primarily found in its intact mature form but we also found a mass corresponding to an N-terminally truncated human CXCL11, lacking the first two amino acids FP, indicating that this chemokine is a substrate for dipeptidylpeptidase IV. Interestingly, this same truncation was found when we expressed human CXCL11 in Drosophila S2 cells. The biological activity of this truncated form of CXCL11 was greatly reduced, both in calcium mobilization (using CXCR3 expressing CHO cells) as well as its chemotactic activity for CXCR3-expressing T-cells. It is concluded that detailed information on chemokines at the protein level is important to characterize the exact profile of these chemotactic peptides as modifications can severely alter their biological activity.

Diagnostic and Prognostic Values of Monocyte Chemotactic Protein-1 in Ascitic Fluid of Patients with Spontaneous Bacterial Peritonitis.

PubMed

El-Toukhy, Naglaa; Emam, Sherin M

2016-06-01

Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhotics with ascites. Monocyte chemotactic protien-1 (MCP-1) is a chemotactic factor for monocytes/macrophages, and it activates lymphocytes and neutrophils during infection. This study aimed to evaluate the role of MPC-1 in the pathogenesis of SBP and assess its prognostic value and correlation to disease severity. The study included ninety patients with liver cirrhosis and ascites. Patients were divided into 2 groups: Group I including 45 ascetic patients with SBP (polymorph nuclear cell count (PMN) >= 250 cell/mm3 in ascitic fluid), and Group II including 45 ascetic patients without SBP. Assessment of the severity of liver cirrhosis was done using the modified Child-Pugh and model for end stage liver disease (MELD) scores. Ascetic fluid samples were subjected to total leucocytic count and differential, albumin, protein, glucose, and serum-ascetic albumin gradient analysis Ascetic fluid levels of (MCP-1was measured by ELISA. Higher level was detected in patients with SBP as compared to those without SBP. The number of polymorph nuclear cell count (PMN) >= 250 cell/mm3 in ascitic fluid) was used as gold standard for diagnosis of SBP. The diagnosis sensitivity and specificity of MCP level test were 86.7% and 95.4% respectively at cutoff of122.5ng/ml with accuracy 91%. MCP-1 level showed positive significant correlation with TLC, PMN leucocytes and MELD score. In conclusion, ascitic fluid MCP-1 level could be a reliable test for diagnosis of SBP, and could be used as a prognostic marker due to its positive correlation with the severity of liver disease. Copyright© by the Egyptian Association of Immunologists.

I-309/T cell activation gene-3 chemokine protects murine T cell lymphomas against dexamethasone-induced apoptosis.

PubMed

Van Snick, J; Houssiau, F; Proost, P; Van Damme, J; Renauld, J C

1996-09-15

We have previously reported that cytokines such as IL-9, IL-4, and IL-6 protect murine thymic lymphoma cell lines against dexamethasone-induced apoptosis. A similar activity, which could not be ascribed to any of these factors, was found in a number of human T cell supernatants that enabled mouse BW5147 thymic lymphoma not only to escape apoptosis but also to maintain proliferation. The protein responsible for this activity was purified to homogeneity from the culture medium of activated leukemic T cells and was found to be identical with the I-309 chemokine. Half-maximal anti-apoptotic activity was obtained with approximately 1 ng/ml, a concentration considerably lower than that required for the monocyte chemotactic activity of this molecule, as measured on THP-1 cells. The purified I-309 also improved the survival of two other mouse thymic lymphoma cell lines. This activity was as potent as that of IL-9, which was the strongest anti-apoptotic factor found to date for these cells. Similar results were obtained for BW5147 cells with recombinant I-309 and with T cell activation gene-3, the murine homologue of I-309, but not with other members of the chemokine family, including IL-8, neutrophil-activating peptide-2, granulocyte chemotactic protein-2, macrophage inflammatory protein-1a, RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), and MCP-2. MCP-3, however, showed a minor, but significant effect in this model. Unlike that of IL-9, the activity of I-309 was completely inhibited in the presence of pertussis toxin, indicating the involvement of a G protein in this process.

Dimethyl Sulfoxide (DMSO) Increases Percentage of CXCR4(+) Hematopoietic Stem/Progenitor Cells, Their Responsiveness to an SDF-1 Gradient, Homing Capacities, and Survival.

PubMed

Jarocha, Danuta; Zuba-Surma, Ewa; Majka, Marcin

2016-01-01

Cryopreservation of bone marrow (BM), mobilized peripheral blood (mPB), and cord blood (CB) hematopoietic stem/progenitor cells (HSPCs) is a routine procedure before transplantation. The most commonly used cryoprotectant for HSPCs is dimethyl sulfoxide (DMSO). The objective of this study was to evaluate the influence of DMSO on surface receptor expression and chemotactic activities of HSPCs. We found that 10 min of incubation of human mononuclear cells (MNCs) with 10% DMSO significantly increases the percentage of CXCR4(+), CD38(+), and CD34(+) cells, resulting in an increase of CD34(+), CD34(+)CXCR4(+), and CD34(+)CXCR4(+)CD38(-) subpopulations. Furthermore, DMSO significantly increased chemotactic responsiveness of MNCs and CXCR4(+) human hematopoietic Jurkat cell line to a stromal cell-derived factor-1 (SDF-1) gradient. Furthermore, we demonstrated enhanced chemotaxis of human clonogenic progenitor cells to an SDF-1 gradient, which suggests that DMSO directly enhances the chemotactic responsiveness of early human progenitors. DMSO preincubation also caused lower internalization of the CXCR4 receptor. In parallel experiments, we found that approximately 30% more of DMSO-preincubated human CD45(+) and CD45(+)CD34(+) cells homed to the mouse BM 24 h after transplantation in comparison to control cells. Finally, we demonstrated considerably higher (25 days) survival of mice transplanted with DMSO-exposed MNCs than those transplanted with the control cells. We show in this study an unexpected beneficial influence of DMSO on HSPC homing and suggest that a short priming with DMSO before transplantation could be considered a new strategy to enhance cell homing and engraftment.

Renal Amyloidosis: Origin and Clinicopathologic Correlations of 474 Recent Cases

PubMed Central

Said, Samar M.; Sethi, Sanjeev; Valeri, Anthony M.; Leung, Nelson; Cornell, Lynn D.; Fidler, Mary E.; Herrera Hernandez, Loren; Vrana, Julie A.; Theis, Jason D.; Quint, Patrick S.; Dogan, Ahmet

2013-01-01

Summary Background and objectives The kidney is the organ most commonly involved in systemic amyloidosis. This study reports the largest clinicopathologic series of renal amyloidosis. Design, setting, participants, & measurements This study provides characteristics of 474 renal amyloidosis cases evaluated at the Mayo Clinic Renal Pathology Laboratory from 2007 to 2011, including age, sex, serum creatinine, proteinuria, type of amyloid, and tissue distribution according to type. Results The type of amyloid was Ig amyloidosis in 407 patients (85.9%), AA amyloidosis in 33 (7.0%), leukocyte chemotactic factor 2 amyloidosis in 13 (2.7%), fibrinogen A α chain amyloidosis in 6 (1.3%), Apo AI, Apo AII, or Apo AIV amyloidosis in 3 (0.6%), combined AA amyloidosis/Ig heavy and light chain amyloidosis in 1 (0.2%), and unclassified in 11 (2.3%). Laser microdissection/mass spectrometry, performed in 147 cases, was needed to determine the origin of amyloid in 74 of the 474 cases (16%), whereas immunofluorescence failed to diagnose 28 of 384 light chain amyloidosis cases (7.3%). Leukocyte chemotactic factor 2 amyloidosis and Apo AI, Apo AII, or Apo AIV amyloidosis were characterized by diffuse interstitial deposition, whereas fibrinogen A α chain amyloidosis showed obliterative glomerular involvement. Compared with other types, Ig amyloidosis was associated with lower serum creatinine, higher degree of proteinuria, and amyloid spicules. Conclusions In the authors’ experience, the vast majority of renal amyloidosis cases are Ig derived. The newly identified leukocyte chemotactic factor 2 amyloidosis form was the most common of the rarer causes of renal amyloidosis. With the advent of laser microdissection/mass spectrometry for amyloid typing, the origin of renal amyloidosis can be determined in >97% of cases. PMID:23704299

Natural Killer (NK)/melanoma cell interaction induces NK-mediated release of chemotactic High Mobility Group Box-1 (HMGB1) capable of amplifying NK cell recruitment

PubMed Central

Parodi, Monica; Pedrazzi, Marco; Cantoni, Claudia; Averna, Monica; Patrone, Mauro; Cavaletto, Maria; Spertino, Stefano; Pende, Daniela; Balsamo, Mirna; Pietra, Gabriella; Sivori, Simona; Carlomagno, Simona; Mingari, Maria Cristina; Moretta, Lorenzo; Sparatore, Bianca; Vitale, Massimo

2015-01-01

In this study we characterize a new mechanism by which Natural Killer (NK) cells may amplify their recruitment to tumors. We show that NK cells, upon interaction with melanoma cells, can release a chemotactic form of High Mobility Group Box-1 (HMGB1) protein capable of attracting additional activated NK cells. We first demonstrate that the engagement of different activating NK cell receptors, including those mainly involved in tumor cell recognition can induce the active release of HMGB1. Then we show that during NK-mediated tumor cell killing two HMGB1 forms are released, each displaying a specific electrophoretic mobility possibly corresponding to a different redox status. By the comparison of normal and perforin-defective NK cells (which are unable to kill target cells) we demonstrate that, in NK/melanoma cell co-cultures, NK cells specifically release an HMGB1 form that acts as chemoattractant, while dying tumor cells passively release a non-chemotactic HMGB1. Finally, we show that Receptor for Advanced Glycation End products is expressed by NK cells and mediates HMGB1-induced NK cell chemotaxis. Proteomic analysis of NK cells exposed to recombinant HMGB1 revealed that this molecule, besides inducing immediate chemotaxis, also promotes changes in the expression of proteins involved in the regulation of the cytoskeletal network. Importantly, these modifications could be associated with an increased motility of NK cells. Thus, our findings allow the definition of a previously unidentified mechanism used by NK cells to amplify their response to tumors, and provide additional clues for the emerging role of HMGB1 in immunomodulation and tumor immunity. PMID:26587323

Chemotactic droplet swimmers in complex geometries

NASA Astrophysics Data System (ADS)

Jin, Chenyu; Hokmabad, Babak V.; Baldwin, Kyle A.; Maass, Corinna C.

2018-02-01

Chemotaxis1 and auto-chemotaxis are key mechanisms in the dynamics of micro-organisms, e.g. in the acquisition of nutrients and in the communication between individuals, influencing the collective behaviour. However, chemical signalling and the natural environment of biological swimmers are generally complex, making them hard to access analytically. We present a well-controlled, tunable artificial model to study chemotaxis and autochemotaxis in complex geometries, using microfluidic assays of self-propelling oil droplets in an aqueous surfactant solution (Herminghaus et al 2014 Soft Matter 10 7008-22 Krüger et al 2016 Phys. Rev. Lett. 117). Droplets propel via interfacial Marangoni stresses powered by micellar solubilisation. Moreover, filled micelles act as a chemical repellent by diffusive phoretic gradient forces. We have studied these chemotactic effects in a series of microfluidic geometries, as published in Jin et al (2017 Proc. Natl Acad. Sci. 114 5089-94): first, droplets are guided along the shortest path through a maze by surfactant diffusing into the maze from the exit. Second, we let auto-chemotactic droplet swimmers pass through bifurcating microfluidic channels and record anticorrelations between the branch choices of consecutive droplets. We present an analytical Langevin model matching the experimental data. In a previously unpublished experiment, pillar arrays of variable sizes and shapes provide a convex wall interacting with the swimmer and, in the case of attachment, bending its trajectory and forcing it to revert to its own trail. We observe different behaviours based on the interplay of wall curvature and negative autochemotaxis, i.e. no attachment for highly curved interfaces, stable trapping at large pillars, and a narrow transition region where negative autochemotaxis makes the swimmers detach after a single orbit.

Bacteria Interactions with Dying Diatoms

NASA Astrophysics Data System (ADS)

Smriga, S.; Juarez, G.; Fernandez, V.; Stocker, R.

2016-02-01

Dying phytoplankton are surrounded by microscale gradients of dissolved organic matter (DOM) that can attract bacteria. These 'phycospheres' may impact the trophic transfer of DOM in the marine microbial food web and enable the growth of bacterial populations, yet these effects remain poorly quantified particularly in relation to the physiological state of the phytoplankton. We dissected phycosphere interactions at unprecedented spatial and temporal resolution using the model diatom Thalassiosira weissflogii and the bacterium Marinobacter adhaerans. Diatom stress was stimulated by addition of polyunsaturated aldehyde (PUA) and both diatom and bacterial responses were captured via time-lapse fluorescence microscopy. We found that stressed diatoms underwent lysis 10-15 h after PUA treatment. Coordinated with the timing of this transition into phytodetritus, wild-type Marinobacter accumulated via chemotaxis near the diatoms immediately following lysis. In contrast, at lysis there was no accumulation of either a non-chemotactic or a non-motile mutant of Marinobacter, pointing to behavioral rather than demographic responses as drivers for the accumulation. Despite the lack of response, non-chemotactic as well as non-swimming bacterial cells that by chance attached to or were located near (<30 µm) stressed diatoms experienced more growth than cells further afield. Growth within the phycosphere was even greater after diatom lysis. Through quantification at the microscale, these results reveal that chemotaxis may precede rapid bacterial attachment to stressed and dying diatoms and may be integral to the microbial colonization of new phytodetritus during phytoplankton blooms and bloom collapses in coastal ecosystems. Even while chemotactic cells retain a growth advantage given their ability to sense and respond to lysis events, phycosphere DOM provides growth benefits to both motile and non-motile taxa that become attached to or happen to be co-located with new phytodetrital particles, thus likely influencing the composition of particle-attached microbial communities.

Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B.

PubMed

Irukayama-Tomobe, Yoko; Tanaka, Hirokazu; Yokomizo, Takehiko; Hashidate-Yoshida, Tomomi; Yanagisawa, Masashi; Sakurai, Takeshi

2009-03-10

GPR109B (HM74) is a putative G protein-coupled receptor (GPCR) whose cognate ligands have yet to be characterized. GPR109B shows a high degree of sequence similarity to GPR109A, another GPCR that was identified as a high-affinity nicotinic acid (niacin) receptor. However, the affinity of nicotinic acid to GPR109B is very low. In this study, we found that certain aromatic D-amino acids, including D-phenylalanine, D-tryptophan, and the metabolite of the latter, D-kynurenine, decreased the activity of adenylate cyclase in cells transfected with GPR109B cDNA through activation of pertussis toxin (PTX)-sensitive G proteins. These D-amino acids also elicited a transient rise of intracellular Ca(2+) level in cells expressing GPR109B in a PTX-sensitive manner. In contrast, these D-amino acids did not show any effects on cells expressing GPR109A. We found that the GPR109B mRNA is abundantly expressed in human neutrophils. D-phenylalanine and D-tryptophan induced a transient increase of intracellular Ca(2+) level and a reduction of cAMP levels in human neutrophils. Furthermore, knockdown of GPR109B by RNA interference inhibited the D-amino acids-induced decrease of cellular cAMP levels in human neutrophils. These D-amino acids induced chemotactic activity of freshly prepared human neutrophils. We also found that D-phenylalanine and D-tryptophan induced chemotactic responses in Jurkat cells transfected with the GPR109B cDNA but not in mock-transfected Jurkat cells. These results suggest that these aromatic D-amino acids elicit a chemotactic response in human neutrophils via activation of GPR109B.

Sperm chemotaxis in siphonophores. II. Calcium-dependent asymmetrical movement of spermatozoa induced by the attractant.

PubMed

Cosson, M P; Carré, D; Cosson, J

1984-06-01

Spermatozoa from siphonophores have been shown to be attracted towards an extracellular structure, the cupule, which covers the predetermined site of fertilization of the egg. Observations on sperm behaviour during the chemotactic response show that spermatozoa describe trajectories of large diameter (700-1000 micron) while far from the cupule, and of smaller diameter (200 micron) in the cupule area. The transition between the two types of swimming occurs progressively when spermatozoa cross a 3 mm wide area around the cupule. After a few minutes 99% of the spermatozoa keep swimming around the attractant source, following circular paths 150-200 micron in diameter. In the absence of the attractant, comparable modifications of sperm trajectories are observed in the presence of the ionophore A23187 and high calcium concentrations. In the presence of 10(-2) M calcium ions, A23187-treated spermatozoa describe trajectories 200 micron in diameter, which increase up to 800 micron at lower calcium concentrations (10(-6) M). In the absence of calcium ions, spermatozoa swim across the cupule area without modification of their trajectories and no sperm accumulation can be detected. This requirement of the chemotactic response for calcium ions is observed either with fresh cupules stuck on the eggs, with cupules separated from the eggs, or with cupule extracts. Moreover, a soluble component fractionated from the cupule induces, when diluted in sea water, a reduction in the size of the sperm trajectories and this also requires calcium ions. The present data show that the chemotactic response of siphonophore sperm, which requires millimolar concentrations of calcium ions, occurs through a non-transient induction of increased asymmetry of the flagellar waveform. It is proposed that the natural attractant operates to produce an increase in the intraaxonemal calcium concentration.

MHC Class II Activation and Interferon-γ Mediate the Inhibition of Neutrophils and Eosinophils by Staphylococcal Enterotoxin Type A (SEA).

PubMed

Ferreira-Duarte, Ana P; Pinheiro-Torres, Anelize S; Anhê, Gabriel F; Condino-Neto, Antônio; Antunes, Edson; DeSouza, Ivani A

2017-01-01

Staphylococcal enterotoxins are classified as superantigens that act by linking T-cell receptor with MHC class II molecules, which are expressed on classical antigen-presenting cells (APC). Evidence shows that MHC class II is also expressed in neutrophils and eosinophils. This study aimed to investigate the role of MHC class II and IFN-γ on chemotactic and adhesion properties of neutrophils and eosinophils after incubation with SEA. Bone marrow (BM) cells obtained from BALB/c mice were resuspended in culture medium, and incubated with SEA (3-30 ng/ml; 1-4 h), after which chemotaxis and adhesion were evaluated. Incubation with SEA significantly reduced the chemotactic and adhesive responses in BM neutrophils activated with IL-8 (200 ng/ml). Likewise, SEA significantly reduced the chemotactic and adhesive responses of BM eosinophils activated with eotaxin (300 ng/ml). The inhibitory effects of SEA on cell chemotaxis and adhesion were fully prevented by prior incubation with an anti-MHC class II blocking antibody (2 μg/ml). SEA also significantly reduced the intracellular Ca 2+ levels in IL-8- and eotaxin-activated BM cells. No alterations of MAC-1, VLA4, and LFA-1α expressions were observed after SEA incubation. In addition, SEA elevated by 3.5-fold ( P < 0.05) the INF-γ levels in BM cells. Incubation of BM leukocytes with IFN-γ (10 ng/ml, 2 h) reduced both neutrophil and eosinophil chemotaxis and adhesion, which were prevented by prior incubation with anti-MHC class II antibody (2 μg/ml). In conclusion, SEA inhibits neutrophil and eosinophil by MHC class II-dependent mechanism, which may be modulated by concomitant release of IFN-γ.

21 CFR 1316.54 - Prehearing conference.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Prehearing conference. 1316.54 Section 1316.54 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE ADMINISTRATIVE FUNCTIONS... to be called. (e) The advance submission at the prehearing conference of all documentary evidence and...

Conference on Functional Literacy in the Community College Setting (Los Alamitos, California, July 1978).

ERIC Educational Resources Information Center

Knoell, Dorothy M.; And Others

The conference papers included in this collection address issues of concern to literacy development in the community college. "Functional Literacy and Persistence in the Community College," by Dorothy M. Knoell, raises questions about student persistence in the absence of requisite skills. "Training Perspective on Functional…

Chemotactic selection of pollutant degrading soil bacteria

DOEpatents

Hazen, Terry C.

1994-01-01

A method for identifying soil microbial strains which may be bacterial degraders of pollutants comprising the steps of placing a concentration of a pollutant in a substantially closed container, placing the container in a sample of soil for a period of time ranging from one minute to several hours, retrieving the container, collecting the contents of the container, and microscopically determining the identity of the bacteria present. Different concentrations of the pollutant can be used to determine which bacteria respond to each concentration. The method can be used for characterizing a polluted site or for looking for naturally occurring biological degraders of the pollutant. Then bacteria identified as degraders of the pollutant and as chemotactically attracted to the pollutant are used to inoculate contaminated soil. To enhance the effect of the bacteria on the pollutant, nutrients are cyclicly provided to the bacteria then withheld to alternately build up the size of the bacterial colony or community and then allow it to degrade the pollutant.

Chemotactic selection of pollutant degrading soil bacteria

DOEpatents

Hazen, T.C.

1991-03-04

A method is described for identifying soil microbial strains which may be bacterial degraders of pollutants. This method includes: Placing a concentration of a pollutant in a substantially closed container; placing the container in a sample of soil for a period of time ranging from one minute to several hours; retrieving the container and collecting its contents; microscopically determining the identity of the bacteria present. Different concentrations of the pollutant can be used to determine which bacteria respond to each concentration. The method can be used for characterizing a polluted site or for looking for naturally occurring biological degraders of the pollutant. Then bacteria identified as degraders of the pollutant and as chemotactically attracted to the pollutant are used to innoculate contaminated soil. To enhance the effect of the bacteria on the pollutant, nutrients are cyclicly provided to the bacteria then withheld to alternately build up the size of the bacterial colony or community and then allow it to degrade the pollutant.

Simulation of Paramecium Chemotaxis Exposed to Calcium Gradients.

PubMed

Sarvestani, Ali N; Shamloo, Amir; Ahmadian, Mohammad Taghi

2016-06-01

Paramecium or other ciliates have the potential to be utilized for minimally invasive surgery systems, making internal body organs accessible. Paramecium shows interesting responses to changes in the concentration of specific ions such as K(+), Mg(2+), and Ca(2+) in the ambient fluid. Some specific responses are observed as, changes in beat pattern of cilia and swimming toward or apart from the ion source. Therefore developing a model for chemotactic motility of small organisms is necessary in order to control the directional movements of these microorganisms before testing them. In this article, we have developed a numerical model, investigating the effects of Ca(2+) on swimming trajectory of Paramecium. Results for Ca(2+)-dependent chemotactic motility show that calcium gradients are efficient actuators for controlling the Paramecium swimming trajectory. After applying a very low Ca(2+) gradient, a directional chemotaxis of swimming Paramecium is observable in this model. As a result, chemotaxis is shown to be an efficient method for controlling the propulsion of these small organisms.

Adaptability of non-genetic diversity in bacterial chemotaxis

PubMed Central

Frankel, Nicholas W; Pontius, William; Dufour, Yann S; Long, Junjiajia; Hernandez-Nunez, Luis; Emonet, Thierry

2014-01-01

Bacterial chemotaxis systems are as diverse as the environments that bacteria inhabit, but how much environmental variation can cells tolerate with a single system? Diversification of a single chemotaxis system could serve as an alternative, or even evolutionary stepping-stone, to switching between multiple systems. We hypothesized that mutations in gene regulation could lead to heritable control of chemotactic diversity. By simulating foraging and colonization of E. coli using a single-cell chemotaxis model, we found that different environments selected for different behaviors. The resulting trade-offs show that populations facing diverse environments would ideally diversify behaviors when time for navigation is limited. We show that advantageous diversity can arise from changes in the distribution of protein levels among individuals, which could occur through mutations in gene regulation. We propose experiments to test our prediction that chemotactic diversity in a clonal population could be a selectable trait that enables adaptation to environmental variability. DOI: http://dx.doi.org/10.7554/eLife.03526.001 PMID:25279698

Mucorales species activation of a serum leukotactic factor.

PubMed Central

Marx, R S; Forsyth, K R; Hentz, S K

1982-01-01

Previous studies have suggested that the focal accumulation of phagocytic leukocytes is an important feature of the host response in mucormycosis. To ascertain the basis for this influx of inflammatory cells, we evaluated the effect of members of the order Mucorales, including species from the genera Rhizopus, Absidia, and Mucor, on the chemotactic activity of normal human serum for neutrophils and monocytes. Both hyphae and spores produced concentration-dependent chemotaxigenesis in serum to a maximum level equivalent to that produced by zymosan activation of serum. Chemotactic activity was similar for live and heat-killed hyphae. No leukotactic activity was demonstrated in the absence of serum. The pretreatment of serum with anti-C3 antibody, heating at 56 degrees C, or 0.01 M EDTA abolished the activity. The pretreatment of serum with 0.01 M ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid did not abolish the activity. These data provide evidence that the leukotactic activity of Mucorales species is generated through the alternative complement pathway. PMID:6759409

The development of human mast cells. An historical reappraisal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribatti, Domenico, E-mail: domenico.ribatti@uniba.it

2016-03-15

The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34{sup +}/CD117{sup +}/CD13{sup +}multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, differentmore » MC phenotypes can develop in different tissues and organs. - Highlights: • Human mast cells originate from CD34/CD117/CD13 positive multipotent hematopoietic progenitors. • Stem cell factor is a major chemotactic factor for mast cells and their progenitors. • Different mast cell phenotypes can develop in different tissues and organs.« less

Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum

PubMed Central

Ibarra-Meneses, Ana V.; Sanchez, Carmen; Alvar, Jorge; Moreno, Javier; Carrillo, Eugenia

2017-01-01

New biomarkers are needed to identify asymptomatic Leishmania infection as well as immunity following vaccination or treatment. With the aim of finding a robust biomarker to assess an effective cellular immune response, monocyte chemotactic protein 1 (MCP-1) was examined in plasma from soluble Leishmania antigen (SLA)-stimulated whole blood collected from subjects living in a Leishmania infantum-endemic area. MCP-1, expressed 110 times more strongly than IL-2, identified 87.5% of asymptomatic subjects and verified some asymptomatic subjects close to the cutoff. MCP-1 was also significantly elevated in all patients cured of visceral leishmaniasis (VL), unlike IL-2, indicating the specific memory response generated against Leishmania. These results show MCP-1 to be a robust candidate biomarker of immunity that could be used as a marker of cure and to both select and follow the population in vaccine phase I–III human clinical trials with developed rapid, easy-to-use field tools. PMID:29033933

Calaxin drives sperm chemotaxis by Ca2+-mediated direct modulation of a dynein motor

PubMed Central

Mizuno, Katsutoshi; Shiba, Kogiku; Okai, Masahiko; Takahashi, Yusuke; Shitaka, Yuji; Oiwa, Kazuhiro; Tanokura, Masaru; Inaba, Kazuo

2012-01-01

Sperm chemotaxis occurs widely in animals and plants and plays an important role in the success of fertilization. Several studies have recently demonstrated that Ca2+ influx through specific Ca2+ channels is a prerequisite for sperm chemotactic movement. However, the regulator that modulates flagellar movement in response to Ca2+ is unknown. Here we show that a neuronal calcium sensor, calaxin, directly acts on outer-arm dynein and regulates specific flagellar movement during sperm chemotaxis. Calaxin inhibition resulted in significant loss of sperm chemotactic movement, despite normal increases in intracellular calcium concentration. Using a demembranated sperm model, we demonstrate that calaxin is essential for generation and propagation of Ca2+-induced asymmetric flagellar bending. An in vitro motility assay revealed that calaxin directly suppressed the velocity of microtubule sliding by outer-arm dynein at high Ca2+ concentrations. This study describes the missing link between chemoattractant-mediated Ca2+ signaling and motor-driven microtubule sliding during sperm chemotaxis. PMID:23169663

Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

PubMed

Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

2006-01-01

Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico.

PubMed

Larsen, Christopher P; Beggs, Marjorie L; Wilson, Jon D; Lathrop, Sarah L

2016-06-01

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population.

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

PubMed Central

Cakmak, Hakan; Basar, Murat; Seval-Celik, Yasemin; Osteen, Kevin G.; Duleba, Antoni J.; Taylor, Hugh S.; Lockwood, Charles J.; Arici, Aydin

2012-01-01

Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future. PMID:22267540

3 CFR - Delegation of a Certain Function and Authority Conferred Upon the President by Section 1235(c) of...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Delegation of a Certain Function and Authority Conferred Upon the President by Section 1235(c) of the Ike Skelton National Defense Authorization Act for Fiscal Year 2011 Presidential Documents Other Presidential Documents Memorandum of January 5, 2012 Delegation of a Certain Function and Authority...

Sixth National Conference on Citizenship.

ERIC Educational Resources Information Center

Department of Justice, Washington, DC.

The document presents proceedings from the sixth in a series of annual national citizenship conferences. Held in Washington, D.C. in 1951, the conference served as a forum where educational, political, business, religious, labor, civic, and communications leaders could explore functions and duties of American citizenship. The theme of the…

Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.

PubMed

Goldsammler, Michelle; Merhi, Zaher; Buyuk, Erkan

2018-05-09

Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.

Leader Training Conference Report.

ERIC Educational Resources Information Center

Michigan-Ohio Regional Educational Lab., Inc., Detroit.

The purpose of this conference was to prepare key people in the field of education to function as inservice education leaders in their respective settings. It called for participants to learn what the MOREL inservice education program is and what it hopes to accomplish, to identify the role and functions of the inservice education leader, and to…

Caring, Conversing, and Realizing Values: New Directions in Language Studies

ERIC Educational Resources Information Center

Hodges, Bert H.; Steffensen, Sune V.; Martin, James E.

2012-01-01

Language serves many functions for humans, but three of the most important are coordination, learning, and friendship. All of those functions were well served by the conversations from which this special issue emerged, a conference, "Grounding language in perception and (inter) action", held at Gordon College in June 2009. The conference brought…

Mononuclear Phagocyte-Mediated Antifungal Immunity: The Role of Chemotactic Receptors and Ligands

PubMed Central

Swamydas, Muthulekha; Break, Timothy J.; Lionakis, Michail S.

2015-01-01

Over the past two decades, fungal infections have emerged as significant causes of morbidity and mortality in patients with hematological malignancies, hematopoietic stem cell or solid organ transplantation and acquired immunodeficiency syndrome. Besides neutrophils and CD4+ T lymphocytes, which have long been known to play an indispensable role in promoting protective antifungal immunity, mononuclear phagocytes are now being increasingly recognized as critical mediators of host defense against fungi. Thus, a recent surge of research studies has focused on understanding the mechanisms by which resident and recruited monocytes, macrophages and dendritic cells accumulate and become activated at the sites of fungal infection. Herein, we critically review how a variety of G-protein coupled chemoattractant receptors and their ligands mediate mononuclear phagocyte recruitment and effector function during infection by the most common human fungal pathogens. PMID:25715741

Argumentation in a Multi Party Asynchronous Computer Mediated Conference: A Generic Analysis

ERIC Educational Resources Information Center

Coffin, Caroline; Painter, Clare; Hewings, Ann

2005-01-01

This paper draws on systemic functional linguistic genre analysis to illuminate the way in which post graduate applied linguistics students structure their argumentation within a multi party asynchronous computer mediated conference. Two conference discussions within the same postgraduate course are compared in order to reveal the way in which…

New ergonomic and functional design of digital conferencing rooms in a clinical environment

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Amato, Carlos L.; McGill, D. Ric; Liu, Brent J.; Balbona, Joseph A.; McCoy, J. Michael

2003-05-01

Clinical conferences and multidisciplinary medical rounds play a major role in patient management and decision-making relying on presentation of variety of documents: films, charts, videotapes, graphs etc. These conferences and clinical rounds are often carried out in conferencing rooms or department libraries that are usually not suitable for presentation of the data in electronic format. In most instances digital projection equipment is added to existing rooms without proper consideration to functional, ergonomic, acoustical, spatial and environmental requirements. Also, in large academic institutions, the conference rooms serve multiple purposes including as classrooms for teaching and education of students and for administrative meetings among managers and staff. In the migration toward a fully digital hospital we elected to analyze the functional requirements and optimize the ergonomic design of conferencing rooms that can accommodate clinical rounds, multidisciplinary reviews, seminars, formal lectures and department meetings. 3D computer simulation was used for better evaluation and analysis of spatial and ergonomic parameters and for gathering opinions and input from users on different design options. A critical component of the design is the understanding of the different workflow and requirements of different types of conferences and presentations that can be carried out in these conference rooms.

CHEMOTACTIC ROLE OF NEUROTROPIN 3 IN THE EMBRYONIC TESTIS THAT FACILITATES MORPHOLOGICAL MALE SEX DETERMINATION. (R827405)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Characterization and Reactivity of Broiler Chicken Sera to Selected Recombinant Campylobacter jejuni Chemotactic Proteins

USDA-ARS?s Scientific Manuscript database

Campylobacter jejuni, a Gram-negative rod bacterium, is the leading causative agent of human acute bacterial gastroenteritis worldwide. Consumption and handling of raw or undercooked poultry are regarded as a major source for human infection. Because bacterial chemotaxis guides microorganisms to c...

THE EFFECTS OF COMBINATORIAL EXPOSURE OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES ON AIRWAY EPITHELIAL CELL RELEASE OF CHEMOTACTIC MEDIATORS

EPA Science Inventory

Asthma is a chronic inflammatory disorder of the airways affecting nearly 15 million individuals nationally. Within the inflamed asthmatic airway there exist complex interactions between many cells and the cytokines they release, in particular mast cells, eosinophils, T-lymphocy...

Leader Training Conference Report. (Second, February 3-19, 1969).

ERIC Educational Resources Information Center

Michigan-Ohio Regional Educational Lab., Inc., Detroit.

The purpose of this conference was to prepare key people in the field of education to function as inservice education leaders in their respective settings. The design called for participants to learn what the MOREL inservice education program is and what it hopes to accomplish, to identify the role and functions of the inservice education leader,…

77 FR 3367 - Delegation of a Certain Function and Authority Conferred Upon the President by Section 1235(c) of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

... Armed Services, Foreign Relations, Homeland Security and Governmental Affairs, and Appropriations of the... Section 1235(c) of the Ike Skelton National Defense Authorization Act for Fiscal Year 2011 Memorandum for... function and authority conferred upon the President by section 1235(c) of the Ike Skelton National Defense...

Functional Capacity Evaluation Research: Report from the Third International Functional Capacity Evaluation Research Meeting.

PubMed

Edelaar, M J A; Gross, D P; James, C L; Reneman, M F

2018-03-01

Purpose Based on the success of the first two conferences the Third International FCE Research Conference was held in The Netherlands on September 29, 2016. The aim was to provide ongoing opportunity to share and recent FCE research and discuss its implications. Methods Invitations and call for abstracts were sent to previous attendees, researchers, practicing FCE clinicians and professionals. Fifteen abstracts were selected for presentation. The FCE research conference contained two keynote lectures. Results 54 participants from 12 countries attended the conference where 15 research projects and 2 keynote lectures were presented. The conference provided an opportunity to present and discuss recent FCE research, and provided a forum for discourse related to FCE use. Conference presentations covered aspects of practical issues in administration and interpretation; protocol reliability and validity; consideration of specific injury populations; and a focused discussion on proposed inclusion of work physiology principles in FCE testing with the Heart Rate Reserve Method. Details of this Third International FCE Research Conference are available from http://repro.rcnheliomare.nl/FCE.pdf . Conclusions Researchers, clinicians, and other professionals in the FCE area have a common desire to further improve the content and quality of FCE research and to collaborate to further develop research across systems, cultures and countries. A fourth, 2-day, International FCE research conference will be held in Valens, Switzerland in August or September 2018. A 'FCE research Society' will be developed.

Neutrophil-derived chemokines on the road to immunity.

PubMed

Tecchio, Cristina; Cassatella, Marco A

2016-04-01

During recent years, it has become clear that polymorphonuclear neutrophils are remarkably versatile cells, whose functions go far beyond phagocytosis and killing. In fact, besides being involved in primary defense against infections-mainly through phagocytosis, generation of toxic molecules, release of toxic enzymes and formation of extracellular traps-neutrophils have been shown to play a role in finely regulating the development and the evolution of inflammatory and immune responses. These latter neutrophil-mediated functions occur by a variety of mechanisms, including the production of newly manufactured cytokines. Herein, we provide a general overview of the chemotactic cytokines/chemokines that neutrophils can potentially produce, either under inflammatory/immune reactions or during their activation in more prolonged processes, such as in tumors. We highlight recent observations generated from studying human or rodent neutrophils in vitro and in vivo models. We also discuss the biological significance of neutrophil-derived chemokines in the context of infectious, neoplastic and immune-mediated diseases. The picture that is emerging is that, given their capacity to produce and release chemokines, neutrophils exert essential functions in recruiting, activating and modulating the activities of different leukocyte populations. Copyright © 2016. Published by Elsevier Ltd.

Hawthorn extract inhibits human isolated neutrophil functions.

PubMed

Dalli, Ernesto; Milara, Javier; Cortijo, Julio; Morcillo, Esteban J; Cosín-Sales, Juan; Sotillo, José Francisco

2008-06-01

Hawthorn extract is a popular herbal medicine given as adjunctive treatment for chronic heart failure. In contrast to the cardiac properties of hawthorn extract, its anti-inflammatory effect has been scarcely investigated. This study examines the effects of a dry extract of leaves and flowers of Crataegus laevigata on various functional outputs of human neutrophils in vitro. Incubation of human neutrophils obtained from peripheral blood of healthy donors with C. laevigata extract (0.75-250 microg/ml) inhibited N-formyl-Met-Leu-Phe (FMLP)-induced superoxide anion generation, elastase release and chemotactic migration with potency values of 43.6, 21.9, and 31.6 microg/ml, respectively. By contrast, serum-opsonized zymosan-induced phagocytosis was unaltered by plant extract. C. laevigata extract (125 microg/ml) reduced FMLP-induced leukotriene B(4) production and lipopolysaccharide-induced generation of tumour necrosis factor-alpha and interleukin-8. Extract inhibited FMLP-induced intracellular calcium signal with potency of 17.4 microg/ml. Extract also markedly inhibited the extracellular calcium entry into calcium-depleted neutrophils, and the thapsigargin-induced intracellular calcium response. In conclusion, C. laevigata extract inhibited various functional outputs of activated human neutrophils which may be relevant to the pathophysiology of cardiac failure.

Report of a Planning Conference for Solar Technology Information Transfer. Jackson, Mississippi, September 7-8, 1978.

ERIC Educational Resources Information Center

Graves, Sid F., Jr., Ed.

This summary of the decisions and recommendations of the Planning Conference for Solar Technology Information Transfer includes a brief discussion of the outline of a functioning solar energy technology network in the State of Mississippi. During the conference, participants recognized current energy information needs and recommended ways to meet…

Report on the 2011 Critical Assessment of Function Annotation (CAFA) meeting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedberg, Iddo

2015-01-21

The Critical Assessment of Function Annotation meeting was held July 14-15, 2011 at the Austria Conference Center in Vienna, Austria. There were 73 registered delegates at the meeting. We thank the DOE for this award. It helped us organize and support a scientific meeting AFP 2011 as a special interest group (SIG) meeting associated with the ISMB 2011 conference. The conference was held in Vienna, Austria, in July 2011. The AFP SIG was held on July 15-16, 2011 (immediately preceding the conference). The meeting consisted of two components, the first being a series of talks (invited and contributed) and discussionmore » sections dedicated to protein function research, with an emphasis on the theory and practice of computational methods utilized in functional annotation. The second component provided a large-scale assessment of computational methods through participation in the Critical Assessment of Functional Annotation (CAFA). The meeting was exciting and, based on feedback, quite successful. There were 73 registered participants. The schedule was only slightly different from the one proposed, due to two cancellations. Dr. Olga Troyanskaya has canceled and we invited Dr. David Jones instead. Similarly, instead of Dr. Richard Roberts, Dr. Simon Kasif gave a closing keynote. The remaining invited speakers were Janet Thornton (EBI) and Amos Bairoch (University of Geneva).« less

Report and Research Agenda of the American Geriatrics Society and National Institute on Aging Bedside-to-Bench Conference on Sleep, Circadian Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health, and Functioning

PubMed Central

Fung, Constance H.; Vitiello, Michael V.; Alessi, Cathy A.; Kuchel, George A.

2016-01-01

The American Geriatrics Society, with support from the National Institute on Aging and other funders, held its eighth Bedside-to-Bench research conference, entitled “Sleep, Circadian Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health and Functioning,” October 4 to 6, 2015, in Bethesda, Maryland. Part of a conference series addressing three common geriatric syndromes—delirium, sleep and circadian rhythm (SCR) disturbance, and voiding dysfunction—the series highlighted relationships and pertinent clinical and pathophysiological commonalities between these three geriatric syndromes. The conference provided a forum for discussing current sleep, circadian rhythm, and aging research; identifying gaps in knowledge; and developing a research agenda to inform future investigative efforts. The conference also promoted networking among developing researchers, leaders in the field of SCR and aging, and National Institutes of Health program personnel. PMID:27858974

Partnering for functional genomics research conference: Abstracts of poster presentations

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-06-01

This reports contains abstracts of poster presentations presented at the Functional Genomics Research Conference held April 16--17, 1998 in Oak Ridge, Tennessee. Attention is focused on the following areas: mouse mutagenesis and genomics; phenotype screening; gene expression analysis; DNA analysis technology development; bioinformatics; comparative analyses of mouse, human, and yeast sequences; and pilot projects to evaluate methodologies.

Cellular vaccines in listeriosis: role of the Listeria antigen GAPDH.

PubMed

Calderón-González, Ricardo; Frande-Cabanes, Elisabet; Bronchalo-Vicente, Lucía; Lecea-Cuello, M Jesús; Pareja, Eduardo; Bosch-Martínez, Alexandre; Fanarraga, Mónica L; Yañez-Díaz, Sonsoles; Carrasco-Marín, Eugenio; Alvarez-Domínguez, Carmen

2014-01-01

The use of live Listeria-based vaccines carries serious difficulties when administrated to immunocompromised individuals. However, cellular carriers have the advantage of inducing multivalent innate immunity as well as cell-mediated immune responses, constituting novel and secure vaccine strategies in listeriosis. Here, we compare the protective efficacy of dendritic cells (DCs) and macrophages and their safety. We examined the immune response of these vaccine vectors using two Listeria antigens, listeriolysin O (LLO) and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), and several epitopes such as the LLO peptides, LLO189-201 and LLO91-99 and the GAPDH peptide, GAPDH1-22. We discarded macrophages as safe vaccine vectors because they show anti-Listeria protection but also high cytotoxicity. DCs loaded with GAPDH1-22 peptide conferred higher protection and security against listeriosis than the widely explored LLO91-99 peptide. Anti-Listeria protection was related to the changes in DC maturation caused by these epitopes, with high production of interleukin-12 as well as significant levels of other Th1 cytokines such as monocyte chemotactic protein-1, tumor necrosis factor-α, and interferon-γ, and with the induction of GAPDH1-22-specific CD4(+) and CD8(+) immune responses. This is believed to be the first study to explore the use of a novel GAPDH antigen as a potential DC-based vaccine candidate for listeriosis, whose efficiency appears to highlight the relevance of vaccine designs containing multiple CD4(+) and CD8(+) epitopes.

Macrophages as drug delivery vehicles for photochemical internalization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Madsen, Steen J.; Gonzalez, Jonathan; Molina, Stephanie; Kumar Nair, Rohit; Hirschberg, Henry

2017-02-01

Targeted delivery of chemotherapeutic drugs to tumor sites is a major challenge in cancer chemotherapy. Cell-based vectorization of therapeutic agents has great potential for cancer therapy in that it can target and maintain an elevated concentration of therapeutic agents at the tumor site and prevent their spread into healthy tissue. The use of circulating cells such as monocytes/macrophages (Ma) offers several advantages compared to nanoparticles as targeted drug delivery vehicles. Ma can be easily obtained from the patient, loaded in vitro with drugs and reinjected into the blood stream. Ma can selectively cross the partially compromised blood-brain barrier surrounding brain tumors and are known to actively migrate to tumors, drawn by chemotactic factors, including hypoxic regions where conventional chemo and radiation therapy are least effective. The utility of Ma as targeted drug delivery vehicles for photochemical internalization (PCI) of tumors was investigated in this study. In vitro studies were conducted using a mixture of F98 rat glioma cells and rat macrophages loaded with a variety of chemotherapeutic agents including bleomycin and 5-fluorouracil. Preliminary data show that macrophages are resistant to both chemotherapeutics while significant toxicity is observed for F98 cells exposed to both drugs. Co-incubation of F98 cells with loaded Ma results in significant F98 toxicity suggesting that Ma are releasing the drugs and, hence providing the rationale for their use as delivery vectors for cancer therapies such as PCI.

Cellular vaccines in listeriosis: role of the Listeria antigen GAPDH

PubMed Central

Calderón-González, Ricardo; Frande-Cabanes, Elisabet; Bronchalo-Vicente, Lucía; Lecea-Cuello, M. Jesús; Pareja, Eduardo; Bosch-Martínez, Alexandre; Fanarraga, Mónica L.; Yañez-Díaz, Sonsoles; Carrasco-Marín, Eugenio; Álvarez-Domínguez, Carmen

2014-01-01

The use of live Listeria-based vaccines carries serious difficulties when administrated to immunocompromised individuals. However, cellular carriers have the advantage of inducing multivalent innate immunity as well as cell-mediated immune responses, constituting novel and secure vaccine strategies in listeriosis. Here, we compare the protective efficacy of dendritic cells (DCs) and macrophages and their safety. We examined the immune response of these vaccine vectors using two Listeria antigens, listeriolysin O (LLO) and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), and several epitopes such as the LLO peptides, LLO189−201 and LLO91−99 and the GAPDH peptide, GAPDH1−22. We discarded macrophages as safe vaccine vectors because they show anti-Listeria protection but also high cytotoxicity. DCs loaded with GAPDH1−22 peptide conferred higher protection and security against listeriosis than the widely explored LLO91−99 peptide. Anti-Listeria protection was related to the changes in DC maturation caused by these epitopes, with high production of interleukin-12 as well as significant levels of other Th1 cytokines such as monocyte chemotactic protein-1, tumor necrosis factor-α, and interferon-γ, and with the induction of GAPDH1−22-specific CD4+ and CD8+ immune responses. This is believed to be the first study to explore the use of a novel GAPDH antigen as a potential DC-based vaccine candidate for listeriosis, whose efficiency appears to highlight the relevance of vaccine designs containing multiple CD4+ and CD8+ epitopes. PMID:24600592

Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

PubMed

Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

2015-01-01

Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

48 CFR 801.602-72 - Exceptions and additional review requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... review of all proposed contracts with hotels or similar facilities for conferences or similar functions... conference at a particular hotel is a procurement and procurement laws and regulations must be followed. ...

48 CFR 801.602-72 - Exceptions and additional review requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... review of all proposed contracts with hotels or similar facilities for conferences or similar functions... conference at a particular hotel is a procurement and procurement laws and regulations must be followed. ...

ARSENITE ACTIVATES KB-DEPENDENT IL-8 GENE EXPRESSION IN AIRWAY EPITHELIM IN THE ABSENCE OF NUCLEAR TRANSLOCATION OF NF-KB

EPA Science Inventory

Airway epithelial cells respond to certain environmental stresses by mounting a proinflammatory response, which is characterized by enhanced synthesis and release of the neutrophil chemotactic and activating factor interleukin-8 (IL-8). IL-8 expression is regulated at the transcr...

Increased monocyte chemotactic protein-1 concentration and monocyte count independently associate with a poor prognosis in dogs with lymphoma.

PubMed

Perry, J A; Thamm, D H; Eickhoff, J; Avery, A C; Dow, S W

2011-03-01

Overexpression of the chemokine monocyte chemotactic protein-1 (MCP-1) has been associated with a poor prognosis in many human cancers. Increased MCP-1 concentrations may promote tumour progression by increasing mobilization of myeloid derived suppressor cells such as immature monocytes and neutrophils. We hypothesized that increased numbers of peripheral neutrophils or monocytes and increased MCP-1 concentrations would predict a worse outcome in dogs with multicentric lymphoma. In this retrospective study involving 26 client-owned dogs diagnosed with lymphoma, we show that peripheral neutrophil and monocyte counts as well as serum MCP-1 concentrations were significantly elevated relative to healthy control animals, and that such increases were associated with a decreased disease-free interval in dogs treated with chemotherapy based on cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP). To our knowledge, this is the first study showing that pretreatment evaluation of monocyte and neutrophil counts can provide important prognostic information in dogs with lymphoma. The mechanisms underlying these observations remain to be determined. © 2010 Blackwell Publishing Ltd.

Lytic and Chemotactic Features of the Plaque-Forming Bacterium KD531 on Phaeodactylum tricornutum

PubMed Central

Chen, Zhangran; Zheng, Wei; Yang, Luxi; Boughner, Lisa A.; Tian, Yun; Zheng, Tianling; Xu, Hong

2017-01-01

Phaeodactylum tricornutum is a dominant bloom forming species and potential biofuel feedstock. To control P. tricornutum bloom or to release lipids from P. tricornutum, we previously screened and identified the lytic bacterium Labrenzia sp. KD531 toward P. tricornutum. In the present study, we evaluated the lytic activity of Labrenzia sp. KD531 on microalgae and investigated its lytic mechanism. The results indicated that the lytic activity of KD531 was temperature- and pH-dependent, but light-independent. In addition to P. tricornutum, KD531 also showed lytic activity against other algal species, especially green algae. A quantitative analysis of algal cellular protein, carbohydrate and lipid content together with measurements of dry weight after exposure to bacteria-infected algal lysate indicated that the bacterium KD531 influenced the algal biomass by disrupting the algal cells. Both chemotactic analysis and microscopic observations of subsamples from different regions of formed plaques showed that KD531 could move toward and then directly contact algal cells. Direct contact between P. tricornutum and KD531 cells was essential for the lytic process. PMID:29312256

Asymmetrical Macromolecular Complex Formation of Lysophosphatidic Acid Receptor 2 (LPA2) Mediates Gradient Sensing in Fibroblasts*

PubMed Central

Ren, Aixia; Moon, Changsuk; Zhang, Weiqiang; Sinha, Chandrima; Yarlagadda, Sunitha; Arora, Kavisha; Wang, Xusheng; Yue, Junming; Parthasarathi, Kaushik; Heil-Chapdelaine, Rick; Tigyi, Gabor; Naren, Anjaparavanda P.

2014-01-01

Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA2) on chemotactic fibroblasts. The onset of decreased LPA2 mobility correlates to the spatial recruitment and coupling to LPA2-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA2 trigger a Ca2+ puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA2 disorganizes the gradient of Ca2+ puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts. PMID:25542932

The directional response of chemotactic cells depends on a balance between cytoskeletal architecture and the external gradient.

PubMed

Wang, Ming-Jie; Artemenko, Yulia; Cai, Wen-Jie; Iglesias, Pablo A; Devreotes, Peter N

2014-11-06

Polarized migrating cells display signal transduction events, such as activation of phosphatidylinositol 3-kinase (PI3K) and Scar/Wave, and respond more readily to chemotactic stimuli at the leading edge. We sought to determine the basis of this polarized sensitivity. Inhibiting actin polymerization leads to uniform sensitivity. However, when human neutrophils were "stalled" by simultaneously blocking actin and myosin dynamics, they maintained the gradient of responsiveness to chemoattractant and also displayed noise-driven PIP3 flashes on the basal membrane, localized toward the front. Thus, polarized sensitivity does not require migration or cytoskeletal dynamics. The threshold for response is correlated with the static F-actin distribution, but not cell shape or volume changes, membrane fluidity, or the preexisting distribution of PI3K. The kinetics of responses to temporal and spatial stimuli were consistent with the local excitation global inhibition model, but the overall direction of the response was biased by the internal axis of polarity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

SU-8 based microdevices to study self-induced chemotaxis in 3D microenvironments

NASA Astrophysics Data System (ADS)

Ayuso, Jose; Monge, Rosa; Llamazares, Guillermo; Moreno, Marco; Agirregabiria, Maria; Berganzo, Javier; Doblaré, Manuel; Ochoa, Iñaki; Fernandez, Luis

2015-05-01

Tissues are complex three-dimensional structures in which cell behaviour is frequently guided by chemotactic signals. Although starvation and nutrient restriction induce many different chemotactic processes, the recreation of such conditions in vitro remains difficult when using standard cell culture equipment. Recently, microfluidic techniques have arisen as powerful tools to mimic such physiological conditions. In this context, microfluidic three-dimensional cell culture systems require precise control of cell/hydrogel location because samples need to be placed within a microchamber without obstruction of surrounding elements. In this article, SU-8 is studied as structural material for the fabrication of complex cell culture devices due to its good mechanical properties, low gas permeability and sensor integration capacity. In particular, this manuscript presents a SU-8 based microdevice designed to create “self-induced” medium starvation, based on the combination of nutrient restriction and natural cell metabolism. Results show a natural migratory response towards nutrient source, showing how cells adapt to their own microenvironment modifications. The presented results demonstrate the SU-8 potential for microdevice fabrication applied to cell culture.

Form Follows Function: Designer Chemistry at the 52nd Bürgenstock Conference.

PubMed

Heretsch, Philipp

2017-07-24

The 52nd Bürgenstock Conference on Stereochemistry took place from April 30-May 4, 2017, and showed how chemistry and design go hand-in-hand (as reflected in the image of the Bauhausarchiv in Berlin). In this Conference Report, Philipp Heretsch outlines the program. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Random Fields and Collective Effects in Molecular Magnets

DTIC Science & Technology

2018-01-29

longitudinal fields the final state consists of only partially reversed spins. Further, we measured the front speed as a function of applied magnetic...field. The theory of magnetic deflagration, together with a modification that takes into account the partial spin reversal, fits the transverse field...Conference Paper or Presentation Conference Name: APS March Meeting 2016 Conference Location: Baltimore, Paper Title: Time-resolved Measurements

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation

PubMed Central

Mendez-Enriquez, E; Melendez, Y; Martinez, F; Baay, G; Huerta-Yepez, S; Gonzalez-Bonilla, C; Fortoul, T I; Soldevila, G; García-Zepeda, E A

2008-01-01

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides. PMID:18336592

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation.

PubMed

Mendez-Enriquez, E; Melendez, Y; Martinez, F; Baay, G; Huerta-Yepez, S; Gonzalez-Bonilla, C; Fortoul, T I; Soldevila, G; García-Zepeda, E A

2008-05-01

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides.

Localization of palmitoylated and activated G protein α-subunit in Dictyostelium discoideum.

PubMed

Alamer, Sarah; Kageyama, Yusuke; Gundersen, Robert E

2018-06-01

Guanine nucleotide-binding proteins (G proteins) act as molecular switches to regulate many fundamental cellular processes. The lipid modification, palmitoylation, can be considered as a key factor for proper G protein function and plasma membrane localization. In Dictyostelium discoidum, Gα2 is essential for the chemotactic response to cAMP in their developmental life cycle. However, the regulation of Gα2 with respect to palmitoylation, activation and Gβγ association is less clear. In this study, Gα2 is shown to be palmitoylated on Cys-4 by [ 3 H]palmitate labeling. Loss of this palmitoylation site results in redistribution of Gα2 within the cell and poor D. discoideum development. Cellular re-localization is also observed for activated Gα2. In the membrane fraction, Gα2-wt (YFP) is highly enriched in a low-density membrane fraction, which is palmitoylation-dependent. Activated Gα2 monomer and heterotrimer are shifted to two different higher-density fractions. These results broaden our understanding of how G protein localization and function are regulated inside the cells. © 2018 Wiley Periodicals, Inc.

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

PubMed Central

Vargas, Pablo; Maiuri, Paolo; Bretou, Marine; Sáez, Pablo J.; Pierobon, Paolo; Maurin, Mathieu; Chabaud, Mélanie; Lankar, Danielle; Obino, Dorian; Terriac, Emmanuel; Raab, Matthew; Thiam, Hawa-Racine; Brocker, Thomas; Kitchen-Goosen, Susan M.; Alberts, Arthur S.; Sunareni, Praveen; Xia, Sheng; Li, Rong; Voituriez, Raphael; Piel, Matthieu; Lennon-Duménil, Ana-Maria

2018-01-01

Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA–mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42–Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4–MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function. PMID:26641718

Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis

NASA Astrophysics Data System (ADS)

Tang, Ming; Wang, Mingjie; Shi, Changji; Iglesias, Pablo A.; Devreotes, Peter N.; Huang, Chuan-Hsiang

2014-10-01

Numerous models explain how cells sense and migrate towards shallow chemoattractant gradients. Studies show that an excitable signal transduction network acts as a pacemaker that controls the cytoskeleton to drive motility. Here we show that this network is required to link stimuli to actin polymerization and chemotactic motility and we distinguish the various models of chemotaxis. First, signalling activity is suppressed towards the low side in a gradient or following removal of uniform chemoattractant. Second, signalling activities display a rapid shut off and a slower adaptation during which responsiveness to subsequent test stimuli decline. Simulations of various models indicate that these properties require coupled adaptive and excitable networks. Adaptation involves a G-protein-independent inhibitor, as stimulation of cells lacking G-protein function suppresses basal activities. The salient features of the coupled networks were observed for different chemoattractants in Dictyostelium and in human neutrophils, suggesting an evolutionarily conserved mechanism for eukaryotic chemotaxis.

Neutrophil trails guide influenza-specific CD8+ T cells in the airways

PubMed Central

Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Capece, Tara; Bae, Seyeon; Miller, Richard; Topham, David J.; Kim, Minsoo

2016-01-01

During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells is unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8+ T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditional knock-out mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8+ T cell recruitment and effector functions. Collectively, these results suggest neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8+ T cell migration and localization in influenza-infected tissues. PMID:26339033

Neutrophil trails guide influenza-specific CD8⁺ T cells in the airways.

PubMed

Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris; Capece, Tara; Bae, Seyeon; Miller, Richard; Topham, David J; Kim, Minsoo

2015-09-04

During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells are unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8(+) T cell-mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8(+) T cell recruitment and effector functions. Collectively, these results suggest that neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8(+) T cell migration and localization in influenza-infected tissues. Copyright © 2015, American Association for the Advancement of Science.

IL-20 bone diseases involvement and therapeutic target potential.

PubMed

Wang, Hsiao-Hsuan; Hsu, Yu-Hsiang; Chang, Ming-Shi

2018-04-24

Millions of people around the world suffer from bone disorders, likes osteoporosis, rheumatoid arthritis (RA), and cancer-induced osteolysis. In general, the bone remodeling balance is determined by osteoclasts and osteoblasts, respectively responsible for bone resorption and bone formation. Excessive inflammation disturbs the activities of these two kinds of cells, typically resulting in the bone loss. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory disorders likes psoriasis, atherosclerosis, cancer, liver fibrosis, and RA. IL-20 has an important role in the regulation of osteoclastogenesis and osteoblastogenesis and is upregulated in several bone-related diseases. The anti-IL-20 monoclonal antibody treatment has a therapeutic potential in several experimental disease models including ovariectomy-induced osteoporosis, cancer-induced osteolysis, and bone fracture. This review article provides an overview describing the IL-20's biological functions in the common bone disorders and thus providing a novel therapeutic strategy in the future.

Rac regulates vascular endothelial growth factor stimulated motility.

PubMed

Soga, N; Connolly, J O; Chellaiah, M; Kawamura, J; Hruska, K A

2001-01-01

During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent. VEGF stimulated chemotaxis, is critically dependent on Rac activation. Osteopontin was a potent matrix activator of motility, and perhaps one explanation for the absence of a VEGF plus osteopontin effect is that osteopontin stimulated motility was inhibitory to the Rac pathway.

In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor.

PubMed

Badie, B; Schartner, J; Klaver, J; Vorpahl, J

1999-05-01

Considered as immune effector cells of the central nervous system, microglia represent a major component of the inflammatory cells found in malignant gliomas. Although their role in brain tumor biology is unclear, accumulation of microglia in malignant brain tumors may be mediated through active secretion of cytokines by glioma cells. Because hepatocyte growth factor/scatter factor (HGF/SF) has been shown to modulate glioma motility through an autocrine mechanism, and because microglia have been reported to express the HGF/SF receptor Met, we hypothesized that microglia recruitment by gliomas may also occur through the secretion of HGF/SF. The effect of glioma cells in augmenting BV-2 murine microglia motility was studied by using an in vitro Boyden chamber migration assay. To determine the chemokines involved in microglia migration, neutralizing monoclonal antibodies against monocyte chemotactic protein-1 and HGF/SF were tested. Immunoblotting was used to check for the expression of HGF/SF by glioma cells, and the expression of Met by BV-2 cells was examined by flow cytometry. BV-2 migration was noted within 7 hours of incubation with both human (U251 MG and U373 MG) and murine (GL261) glioma cell lines. This migration corresponded to HGF/SF secretion by glioma cells and was completely inhibited by neutralizing monoclonal antibody against HGF/SF, but not monocyte chemotactic protein-1. Exposure of BV-2 cells to recombinant HGF/SF, but not monocyte chemotactic protein-1, resulted in their migration and down-regulation of Met in a dose-dependent fashion. HGF/SF, which plays a role in glioma motility and mitogenesis, may also act as a chemokine for microglia and may be responsible for the microglia infiltration in malignant gliomas. This active recruitment of microglia may play an important role in glioma biology.

Control of Human Endometrial Stromal Cell Motility by PDGF-BB, HB-EGF and Trophoblast-Secreted Factors

PubMed Central

Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H. E.; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S.; Bamberger, Ana-Maria; Gellersen, Birgit

2013-01-01

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site. PMID:23349855

Growth-related gene product {alpha}: A chemotactic cytokine for neutrophils in rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koch, A.E.; Pope, R.M.; Shah, M.R.

Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product {alpha} (gro{alpha}) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro{alpha} (mean 5.3 {+-} 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro{alpha} (mean 4.3 {+-} 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10{sup 5}/cells/ml RPMImore » 1640/24 h) produced antigenic gro{alpha} (mean 0.2 {+-} 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-{alpha} (mean 1.3 {+-} 0.3 ng/ml) or IL-1{beta} (mean 2.3 {+-} 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro{alpha}: neutrophils (PMNs) (10{sup 7} cells/ml/24 h) produced 3.7 {+-} 0.7 ng/ml. RA SF mononuclear cells produced gro{alpha}, particularly upon incubation with LPS or PHA. Immunoreactive ST gro{alpha} was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro{alpha} for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro{alpha} plays an important role in the ingress of PMNs into the RA joint. 54 refs., 6 figs., 1 tab.« less

Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages.

PubMed

Wang, Ying; Wang, Gary Z; Rabinovitch, Peter S; Tabas, Ira

2014-01-31

Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell type-specific causation studies in vivo are lacking, and the molecular mechanisms of potential proatherogenic effects remain to be determined. Our aims were to assess the importance of macrophage mitoOS in atherogenesis and to explore the underlying molecular mechanisms. We first validated Western diet-fed Ldlr(-/-) mice as a model of human mitoOS-atherosclerosis association by showing that non-nuclear oxidative DNA damage, a marker of mitoOS in lesional macrophages, correlates with aortic root lesion development. To investigate the importance of macrophage mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6c(hi) monocyte infiltration into lesions, and lower levels of monocyte chemotactic protein-1. The decrease in lesional monocyte chemotactic protein-1 was associated with the suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-κB p65), indicating decreased activation of the proinflammatory NF-κB pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed monocyte chemotactic protein-1 expression by decreasing the activation of the IκB-kinase β-RelA NF-κB pathway. MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-κB-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis.

Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.

PubMed Central

Little, S.; Dean, T.; Bevin, S.; Hall, M.; Ashton, M.; Church, M.; Warner, J.; Shute, J.

1995-01-01

BACKGROUND--Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS--Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS--Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS--The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease. PMID:7491556

Agonist-dependent phosphorylation of N-formylpeptide and activation peptide from the fifth component of C (C5a) chemoattractant receptors in differentiated HL60 cells.

PubMed

Tardif, M; Mery, L; Brouchon, L; Boulay, F

1993-04-15

Attenuation of signaling is a key step in controlling the cytotoxic potential of leukocyte responses to chemotactic factors. Antipeptide antibodies, directed against the N-formyl chemotactic peptide receptor (FPR) and the activation peptide from the fifth component of C (C5a) anaphylatoxin receptor (C5aR) of human neutrophils, were used to analyze the ability of these receptors to be phosphorylated. Our data show that, in granulocyte-like differentiated HL-60 cells, both FPR and C5aR undergo an agonist dose-dependent phosphorylation that reaches completion in less than 2 to 3 min, consistent with the rate and the dose-dependent attenuation of signaling in phagocytes. Therefore, phosphorylation might be one of the possible mechanisms involved in the desensitization process of FPR and C5aR. Addition of either C5a or the protein kinase C activator (PMA) did not appear to induce the phosphorylation of FPR in the absence of FMLP or to modulate the phosphorylation of the latter at low concentrations of agonist. In contrast, although FMLP at a saturating concentration barely stimulated the phosphorylation of unoccupied C5aR, it markedly potentiated C5aR phosphorylation in cells exposed to low concentrations of C5a. Moreover, PMA was able to induce C5aR phosphorylation in the absence of agonist, indicating that protein kinase C or protein kinase C-activated kinase(s) could be involved in the phosphorylation of C5aR. Pretreatment of cells with staurosporine, a potent but nonspecific inhibitor of protein kinase C, resulted in the partial inhibition of both FPR and C5aR phosphorylation induced by saturating concentrations of agonist, suggesting that a kinase different from protein kinase C might be mainly responsible for the phosphorylation of these chemotactic receptors.

Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing.

PubMed

Yoon, Dong Suk; Lee, Yunki; Ryu, Hyun Aae; Jang, Yeonsue; Lee, Kyoung-Mi; Choi, Yoorim; Choi, Woo Jin; Lee, Moses; Park, Kyung Min; Park, Ki Dong; Lee, Jin Woo

2016-07-01

In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications. Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound closure, neovascularization, and thicker granulation. Therefore, we expect that HRP-catalyzed in situ forming GH hydrogels can serve as an injectable/sprayable carrier of various therapeutic agents for wound healing applications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions

PubMed Central

Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

2015-01-01

Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced chemotactic and proangiogenic properties and a significant (p < .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies. Significance The present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. PMID:25979862

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.

PubMed

Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

2015-07-01

: Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced chemotactic and proangiogenic properties and a significant (p < .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies. The present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. ©AlphaMed Press.

Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

PubMed

Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

2013-10-09

Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

MULTISCALE MODELS OF TAXIS-DRIVEN PATTERNING IN BACTERIAL POPULATIONS

PubMed Central

XUE, CHUAN; OTHMER, HANS G.

2009-01-01

Spatially-distributed populations of various types of bacteria often display intricate spatial patterns that are thought to result from the cellular response to gradients of nutrients or other attractants. In the past decade a great deal has been learned about signal transduction, metabolism and movement in E. coli and other bacteria, but translating the individual-level behavior into population-level dynamics is still a challenging problem. However, this is a necessary step because it is computationally impractical to use a strictly cell-based model to understand patterning in growing populations, since the total number of cells may reach 1012 - 1014 in some experiments. In the past phenomenological equations such as the Patlak-Keller-Segel equations have been used in modeling the cell movement that is involved in the formation of such patterns, but the question remains as to how the microscopic behavior can be correctly described by a macroscopic equation. Significant progress has been made for bacterial species that employ a “run-and-tumble” strategy of movement, in that macroscopic equations based on simplified schemes for signal transduction and turning behavior have been derived [14, 15]. Here we extend previous work in a number of directions: (i) we allow for time-dependent signals, which extends the applicability of the equations to natural environments, (ii) we use a more general turning rate function that better describes the biological behavior, and (iii) we incorporate the effect of hydrodynamic forces that arise when cells swim in close proximity to a surface. We also develop a new approach to solving the moment equations derived from the transport equation that does not involve closure assumptions. Numerical examples show that the solution of the lowest-order macroscopic equation agrees well with the solution obtained from a Monte Carlo simulation of cell movement under a variety of temporal protocols for the signal. We also apply the method to derive equations of chemotactic movement that are governed by multiple chemotactic signals. PMID:19784399

Chemotactic peptide fMetLeuPhe induces translocation of the TRPV2 channel in macrophages.

PubMed

Nagasawa, Masahiro; Nakagawa, Yuko; Tanaka, Shigeyasu; Kojima, Itaru

2007-03-01

The present study was conducted to characterize the regulation and function of TRPV2 in macrophages. Among six members of the TRPV family channels, only the expression of TRPV2 was detected in macrophages. We then determined localization of TRPV2 using TtT/M87 macrophages transfected with TRPV2-EGFP. In serum-free condition, most of the TRPV2 signal was located in the cytoplasm and colocalized with the endoplasmic reticulum marker. Treatment with serum induced translocation of some of the TRPV2-EGFP to the plasma membrane. Serum-induced translocation was blocked by transfection of short-form TRPV2 (s-TRPV2) lacking a pore-forming region and the sixth transmembrane domain. Addition of a chemotactic peptide formyl Met-Leu-Phe (fMLP) also induced translocation of TRPV2-EGFP to the plasma membrane. The fMLP-induced translocation was blocked by an inhibitor of PI 3-kinase, LY294002, and pertussis toxin. Whole-cell patch clamp analysis showed a Cs+ current in the TtT/M87 cell, which was blocked by an addition of ruthenium red and transfection of either s-TRPV2 or siRNA for TRPV2. fMLP increased the Cs+ current. fMLP induced a rapid and sustained elevation of cytoplasmic Ca2+ ([Ca2+]C), the sustained phase of which was abolished by removal of extracellular calcium. The sustained elevation of [Ca2+]C was also blocked by ruthenium red, and transfection of either s-TRPV2 or siRNA. Finally, fMLP-induced migration of macrophage was blocked by ruthenium red or transfection of s-TRPV2. These results suggest that fMLP induces translocation of TRPV2 from intracellular compartment to the plasma membrane, and this translocation is critical for fMLP-induced calcium entry. Copyright 2006 Wiley-Liss, Inc.

Summit Conference on Environmental Education, Report and Recommendations. Conference Developed Under the Auspices of the Environmental Education Association of Illinois. Document No. 79/25.

ERIC Educational Resources Information Center

Buckman, Emily

This report documents the recommendations derived from conference attention to five areas of concern: (1) responsibility of all sectors to enhance the individual's ability to make informed decisions on environmental issues; (2) the responsibility of all sectors to share information leading to enhanced ability to function in an environmentally…

On a Parabolic-Elliptic system with chemotaxis and logistic type growth

NASA Astrophysics Data System (ADS)

Galakhov, Evgeny; Salieva, Olga; Tello, J. Ignacio

2016-10-01

We consider a nonlinear PDEs system of two equations of Parabolic-Elliptic type with chemotactic terms. The system models the movement of a biological population ;u; towards a higher concentration of a chemical agent ;w; in a bounded and regular domain Ω ⊂RN for arbitrary N ∈ N. After normalization, the system is as follows

High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis lung carcinoma

USDA-ARS?s Scientific Manuscript database

Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesit...

PREFACE: Functional materials and nanotechnologies (FM&NT-2007)

NASA Astrophysics Data System (ADS)

Sternberg, Andris; Muzikante, Inta

2007-06-01

The International Baltic Sea Region conference Functional Materials and Nanotechnologies (FM&NT-2007) was held in Riga, 2-4 April 2007 in the Institute of Solid State Physics, University of Latvia (ISSP LU). The conference was organized in co-operation with projects ERANET 'MATERA' and EUREKA 'BIONANOCOMPOSITE'. The purpose of the conference was to bring together scientists, engineers and students from universities, research institutes and related industrial companies active in the field of advanced material science and materials technologies trends and future activities. Scientific themes covered in the conference are:

PREFACE: International Conference on Functional Materials and Nanotechnologies 2013 (FM&NT2013)

NASA Astrophysics Data System (ADS)

Nõmmiste, Ergo; Kirm, Marco; Plank, Toomas

2013-12-01

The International Conference Functional Materials and Nanotechnologies (FM&NT - 2013) was held in Tartu, 21-24 April 2013 at the Dorpat Conference Centre. The conference was organised by Institute of Physics, University of Tartu. The FM&NT conference series was started in 2006 by scientists from the Institute of Solid State Physics, University of Latvia. It is an annual conference bringing together researchers from the whole world. The warm and open atmosphere of this scientific conference has turned it into event where people from different fields meet under the common name of functional materials and nanotechnology. It is particularly important for early stage scientists who are looking for new knowledge and contact with people from various fields. Our Latvian colleagues with their success in internationalization made us neighbouring Estonians so envious that we could not withstand proposing that we host the conference in every second year in Estonia. Actually this is in a way the continuation of the idea of the famous Baltic seminars which took place over several decades during the last century. Due to political constraints these seminars were only opened to scientist of the former Eastern European countries, but which were extremely popular and attracted attendees from over the whole Soviet Union. Much fruitful cooperation started from the initial personal contacts of scientists at these seminars held twice per year, once in Latvia and the second time in Estonia. At the last FM&NT 2012 conference, the decision was made that Institute of Physics, University of Tartu would organise the event in Tartu in 2013. Along with traditional topics such as multifunctional materials, nanomaterials, materials for sustainable energy applications and theory, this conference focused on studies using synchrotron radiation and other novel light sources. The number of registered participants from 21 countries was nearly 300. During the three days of the conference 14 invited, 45 oral, and 5 commercial talks were delivered and more than 200 posters were presented. In the framework of conference more than 20 papers were submitted to a topical issue of Physica Scripta. Based on the work presented at the conference, 62 articles are included in this volume of IOP Conference Series: Materials Science and Engineering. Additional information about FM&NT-2013 is available at its homepage http://fmnt.ut.ee/. The Organizing Committee would like to thank all the speakers, contributors, session chairs, referees and other involved staff for their efforts in making FM&NT-2013 successful. Special thanks for their hard work dealing with the conference papers goes to the Guest Editors: Professor Mikhail Brik, Dr Svetlana Zazubovits, Dr Arvo Kikas, Dr Rainer Pärna. The Organizing Committee hopes that Conference gave participants good insight into recent developments in nanotechnology, sustainable energetics, processing and modelling of multifunctional materials and research done using synchrotron radiation or other novel light sources. We sincerely hope that conference has provided support for the sharing of information and has brought together many young and experienced scientists from different fields, leading to fruitful discussions. We hope that all participants had good and memorable time in Tartu. On the behalf of organising committee Professor Ergo Nõmmiste Dr Marco Kirm Dr Toomas Plank The PDF also contains lists of the committees, the conference photograph and the sponsor's logos.

Linking information and people in a social system for academic conferences

NASA Astrophysics Data System (ADS)

Brusilovsky, Peter; Oh, Jung Sun; López, Claudia; Parra, Denis; Jeng, Wei

2017-04-01

This paper investigates the feasibility of maintaining a social information system to support attendees at an academic conference. The main challenge of this work was to create an infrastructure where users' social activities, such as bookmarking, tagging, and social linking could be used to enhance user navigation and maximize the users' ability to locate two important types of information in conference settings: presentations to attend and attendees to meet. We developed Conference Navigator 3, a social conference support system that integrates a conference schedule planner with a social linking service. We examined its potential and functions in the context of a medium-scale academic conference. In this paper, we present the design of the system's socially enabled features and report the results of a conference-based study. Our study demonstrates the feasibility of social information systems for supporting academic conferences. Despite the low number of potential users and the short timeframe in which conferences took place, the usage of the system was high enough to provide sufficient data for social mechanisms. The study shows that most critical social features were highly appreciated and used, and provides direction for further research.

Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

PubMed Central

Perron, Gabriel G.; Whyte, Lyle; Turnbaugh, Peter J.; Goordial, Jacqueline; Hanage, William P.; Dantas, Gautam; Desai, Michael M.

2015-01-01

Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes. PMID:25807523

Nano-sized and micro-sized polystyrene particles affect phagocyte function

PubMed Central

Prietl, B.; Meindl, C.; Roblegg, E.; Pieber, T. R.; Lanzer, G.; Fröhlich, E.

2015-01-01

Adverse effect of nanoparticles may include impairment of phagocyte function. To identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis, cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and myeloperoxidase release, leukocytes isolated from human peripheral blood, monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS particles were taken up passively, while larger CPS particles entered cells actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. Twenty nanometers CPS particles stimulated IL-8 secretion in human monocytes and induced oxidative burst in monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an oxidative burst of granulocytes. At very high concentrations, CPS particles of 20 and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages. Cytotoxic effect could contribute to some of the observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles appear to influence phagocyte function to a greater extent than particles in other sizes. PMID:24292270

Active Brownian motion tunable by light.

PubMed

Buttinoni, Ivo; Volpe, Giovanni; Kümmel, Felix; Volpe, Giorgio; Bechinger, Clemens

2012-07-18

Active Brownian particles are capable of taking up energy from their environment and converting it into directed motion; examples range from chemotactic cells and bacteria to artificial micro-swimmers. We have recently demonstrated that Janus particles, i.e. gold-capped colloidal spheres, suspended in a critical binary liquid mixture perform active Brownian motion when illuminated by light. In this paper, we investigate in more detail their swimming mechanism, leading to active Brownian motion. We show that the illumination-borne heating induces a local asymmetric demixing of the binary mixture, generating a spatial chemical concentration gradient which is responsible for the particle's self-diffusiophoretic motion. We study this effect as a function of the functionalization of the gold cap, the particle size and the illumination intensity: the functionalization determines what component of the binary mixture is preferentially adsorbed at the cap and the swimming direction (towards or away from the cap); the particle size determines the rotational diffusion and, therefore, the random reorientation of the particle; and the intensity tunes the strength of the heating and, therefore, of the motion. Finally, we harness this dependence of the swimming strength on the illumination intensity to investigate the behavior of a micro-swimmer in a spatial light gradient, where its swimming properties are space-dependent.

Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

PubMed

Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David

2018-06-26

The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Exosomes from eosinophils autoregulate and promote eosinophil functions.

PubMed

Cañas, José Antonio; Sastre, Beatriz; Mazzeo, Carla; Fernández-Nieto, Mar; Rodrigo-Muñoz, José Manuel; González-Guerra, Andrés; Izquierdo, Manuel; Barranco, Pilar; Quirce, Santiago; Sastre, Joaquín; Del Pozo, Victoria

2017-05-01

Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma ( n = 58) and healthy volunteers ( n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma. © Society for Leukocyte Biology.

Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity.

PubMed

Karin, Nathan; Razon, Hila

2018-09-01

Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Alves, S. G.; Martins, M. L.

2010-09-01

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.

Nano-sized and micro-sized polystyrene particles affect phagocyte function.

PubMed

Prietl, B; Meindl, C; Roblegg, E; Pieber, T R; Lanzer, G; Fröhlich, E

2014-02-01

Adverse effect of nanoparticles may include impairment of phagocyte function. To identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis, cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and myeloperoxidase release, leukocytes isolated from human peripheral blood, monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS particles were taken up passively, while larger CPS particles entered cells actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. Twenty nanometers CPS particles stimulated IL-8 secretion in human monocytes and induced oxidative burst in monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an oxidative burst of granulocytes. At very high concentrations, CPS particles of 20 and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages. Cytotoxic effect could contribute to some of the observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles appear to influence phagocyte function to a greater extent than particles in other sizes.

Stabilization in a two-species chemotaxis system with a logistic source

NASA Astrophysics Data System (ADS)

Tello, J. I.; Winkler, M.

2012-05-01

We study a system of three partial differential equations modelling the spatio-temporal behaviour of two competitive populations of biological species both of which are attracted chemotactically by the same signal substance. More precisely, we consider the initial-boundary value problem for \\[ \\begin{equation*} \\fl\\left\\{ \\begin{array}{@{}l} u_t= d_1\\Delta u - \\chi_1 \

N-3 and n-6 polyunsaturated fatty acids differentially regulate adipose angiotensinogen and other inflammatory adipokines in part via NF-kB dependent mechanisms

USDA-ARS?s Scientific Manuscript database

Excessive secretion of angiotensinogen (Agt) and other adipokines such as Interleukin-6 (IL-6) and Monocyte chemotactic protein-1 (MCP-1) have been linked to obesity and associated metabolic disorders, with a common feature being inflammation. We have previously shown that n-3 polyunsaturated fatty ...

Characterizing Myeloid Cell Activation in NF1 Vasculopathy

DTIC Science & Technology

2017-07-01

stimulation of its receptor (CCR2) and the generation of reactive oxygen species, which are generated in excessive quantities by neurofibromin-deficient...macrophages via monocyte chemotactic peptide-1 (MCP-1) stimulation of its receptor (CCR2) and the generation of reactive oxygen species, which are...neurofibromatosis; stenosis; aneurysm; MCP-1; CCR2; reactive oxygen species; superoxide; macrophages; monocytes; arteries; cardiovascular disease Major

PREFACE: 10th Joint Conference on Chemistry

NASA Astrophysics Data System (ADS)

2016-02-01

The 10th Joint Conference on Chemistry is an international conference organized by 4 chemistry departments of 4 universities in central Java, Indonesia. The universities are Sebelas Maret University, Diponegoro University, Semarang State University and Soedirman University. The venue was at Solo, Indonesia, at September 8-9, 2015. The total conference participants are 133 including the invited speakers. The conference emphasized the multidisciplinary chemical issue and impact of today's sustainable chemistry which covering the following topics: • Material innovation for sustainable goals • Development of renewable and sustainable energy based on chemistry • New drug design, experimental and theoretical methods • Green synthesis and characterization of material (from molecule to functionalized materials) • Catalysis as core technology in industry • Natural product isolation and optimization

Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing.

PubMed

Joseph, Adrian; Contini, Claudia; Cecchin, Denis; Nyberg, Sophie; Ruiz-Perez, Lorena; Gaitzsch, Jens; Fullstone, Gavin; Tian, Xiaohe; Azizi, Juzaili; Preston, Jane; Volpe, Giorgio; Battaglia, Giuseppe

2017-08-01

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.

Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex-mediated arthritis.

PubMed

van Lent, P L; Licht, R; Dijkman, H; Holthuysen, A E; Berden, J H; van den Berg, W B

2001-11-01

Previously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex-mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.

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.

PubMed

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.

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

PubMed Central

Pailan, Santanu

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

A bacterial pathogen uses dimethylsulfoniopropionate as a cue to target heat-stressed corals.

PubMed

Garren, Melissa; Son, Kwangmin; Raina, Jean-Baptiste; Rusconi, Roberto; Menolascina, Filippo; Shapiro, Orr H; Tout, Jessica; Bourne, David G; Seymour, Justin R; Stocker, Roman

2014-05-01

Diseases are an emerging threat to ocean ecosystems. Coral reefs, in particular, are experiencing a worldwide decline because of disease and bleaching, which have been exacerbated by rising seawater temperatures. Yet, the ecological mechanisms behind most coral diseases remain unidentified. Here, we demonstrate that a coral pathogen, Vibrio coralliilyticus, uses chemotaxis and chemokinesis to target the mucus of its coral host, Pocillopora damicornis. A primary driver of this response is the host metabolite dimethylsulfoniopropionate (DMSP), a key element in the global sulfur cycle and a potent foraging cue throughout the marine food web. Coral mucus is rich in DMSP, and we found that DMSP alone elicits chemotactic responses of comparable intensity to whole mucus. Furthermore, in heat-stressed coral fragments, DMSP concentrations increased fivefold and the pathogen's chemotactic response was correspondingly enhanced. Intriguingly, despite being a rich source of carbon and sulfur, DMSP is not metabolized by the pathogen, suggesting that it is used purely as an infochemical for host location. These results reveal a new role for DMSP in coral disease, demonstrate the importance of chemical signaling and swimming behavior in the recruitment of pathogens to corals and highlight the impact of increased seawater temperatures on disease pathways.

The kampo medicine Daikenchuto inhibits peritoneal fibrosis in mice.

PubMed

Kitamura, Mineaki; Nishino, Tomoya; Obata, Yoko; Oka, Satoru; Abe, Shinichi; Muta, Kumiko; Ozono, Yoshiyuki; Koji, Takehiko; Kohno, Shigeru

2015-01-01

Long-term peritoneal dialysis therapy causes inflammation and histological changes in the peritoneal membrane. Inflammation generally activates fibroblasts and results in fibroblast-myofibroblast differentiation. Heat-shock protein 47 (HSP 47), a collagen-specific molecular chaperone, is localized in myofibroblasts and is involved in the progression of peritoneal fibrosis. Daikenchuto (DKT), a Kampo medicine, is used to prevent postoperative colon adhesion. It inhibits inflammation and HSP 47 expression in the gastrointestinal tract. We examined the effect of DKT on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in mice injected with 0.1% CG dissolved in 15% ethanol. DKT was dissolved in the drinking water. Histological changes were assessed using Masson trichrome staining. Cells expressing α-smooth muscle actin (α-SMA), HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 were examined immunohistochemically. Compared with the control group, the peritoneal tissues of the CG group were markedly thickened, and the number of cells expressing α-SMA, HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 was significantly increased. However, these changes were inhibited in the DKT-treated group. These results indicate that DKT can prevent peritoneal fibrosis by inhibiting inflammation and HSP 47 expression.

Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing

PubMed Central

Joseph, Adrian; Contini, Claudia; Cecchin, Denis; Nyberg, Sophie; Ruiz-Perez, Lorena; Gaitzsch, Jens; Fullstone, Gavin; Tian, Xiaohe; Azizi, Juzaili; Preston, Jane; Volpe, Giorgio; Battaglia, Giuseppe

2017-01-01

In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor–related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems. PMID:28782037

Cyclic stretch augments production of neutrophil chemokines and matrix metalloproteinase-1 in human uterine smooth muscle cells.

PubMed

Zhao, Yin; Koga, Kaori; Osuga, Yutaka; Izumi, Gentaro; Takamura, Masashi; Harada, Miyuki; Hirata, Tetsuya; Hirota, Yasushi; Yoshino, Osamu; Fujii, Tomoyuki; Kozuma, Shiro

2013-03-01

The aim of this study was to investigate the impact of uterine contraction on the immune environment within the uterus during parturition. Uterine smooth muscle cells (USMC) were isolated from uterine myometrial tissues and cultured. The effects of cyclic stretch on mRNA and/or protein expression of IL-8, Groα, and pro-MMP-1 by USMC were measured using RT-PCR and ELISA. Neutrophil chemotactic activity in conditioned media was evaluated using migration assays. To evaluate the effect of progesterone (P(4) ), USMC were pretreated with P(4) for 24 hr. Cyclic stretch increased IL-8 and Groα mRNA and protein and pro-MMP-1 production significantly. Supernatants from stretched cells induced neutrophil chemotactic activity significantly; these effects were abrogated by anti-IL-8 or Groα neutralizing antibodies. Stretch effects were reduced by P(4) . These results suggest that uterine contraction may induce neutrophil infiltration and MMP-1 production, which may contribute to cervical ripening and rupture of membrane. The inhibitory effects of P(4) may explain the mechanism by which progestin prevents preterm labor. © 2012 John Wiley & Sons A/S.

Impact of motility and chemotaxis features of the rhizobacterium Pseudomonas chlororaphis PCL1606 on its biocontrol of avocado white root rot.

PubMed

Polonio, Álvaro; Vida, Carmen; de Vicente, Antonio; Cazorla, Francisco M

2017-06-01

The biocontrol rhizobacterium Pseudomonas chlororaphis PCL1606 has the ability to protect avocado plants against white root rot produced by the phytopathogenic fungus Rosellinia necatrix. Moreover, PCL1606 displayed direct interactions with avocado roots and the pathogenic fungus. Thus, nonmotile (flgK mutant) and non-chemotactic (cheA mutant) derivatives of PCL1606 were constructed to emphasize the importance of motility and chemotaxis in the biological behaviour of PCL1606 during the biocontrol interaction. Plate chemotaxis assay showed that PCL1606 was attracted to the single compounds tested, such as glucose, glutamate, succinate, aspartate and malate, but no chemotaxis was observed to avocado or R. necatrix exudates. Using the more sensitive capillary assay, it was reported that smaller concentrations (1 mM) of single compounds elicited high chemotactic responses, and strong attraction was confirmed to avocado and R. necatrix exudates. Finally, biocontrol experiments revealed that the cheA and fglK derivative mutants reduced root protection against R. necatrix, suggesting an important role for these biological traits in biocontrol by P. chlororaphis PCL1606. [Int Microbiol 20(2):94-104 (2017)]. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

The actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

NASA Astrophysics Data System (ADS)

Westendorf, Christian; Negrete, Jose, Jr.; Bae, Albert; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

2013-03-01

We report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. The averaged F-actin response of many cells to a short-time pulse of cAMP is reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. We systematically exposed a large number of cells to periodic pulse trains. The results indicate a resonance peak at periodic inputs of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the actin regulatory network. To quantitatively test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and Aip1. These served as markers of the F-actin disassembly process and thus allow us to estimate the delay time. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed experimentally. Financial support by the Max-Planck Society and the DFG (SFB 937).

Essential role of protein kinase C zeta in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP.

PubMed

Kuribayashi, Kageaki; Nakamura, Kiminori; Tanaka, Maki; Sato, Tsutomu; Kato, Junji; Sasaki, Katsunori; Takimoto, Rishu; Kogawa, Katsuhisa; Terui, Takeshi; Takayama, Tetsuji; Onuma, Takayuki; Matsunaga, Takuya; Niitsu, Yoshiro

2007-03-26

Under various pathological conditions, including infection, malignancy, and autoimmune diseases, tissues are incessantly exposed to reactive oxygen species produced by infiltrating inflammatory cells. We show augmentation of motility associated with morphological changes of human squamous carcinoma SASH1 cells, human peripheral monocytes (hPMs), and murine macrophage-like cell line J774.1 by superoxide stimulation. We also disclose that motility of hPMs and J774.1 induced by a chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) was inhibited by superoxide dismutase or N-acetylcystein, indicating stimulation of motility by superoxide generated by fMLP stimulation. In these cells, protein kinase C (PKC) zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation. These events were inhibited by dominant-negative PKCzeta in SASH1 cells, myristoylated PKCzeta peptides in hPMs and J774.1, or a specific inhibitor of RhoGTPase in SASH1, hPMs, and J774.1. These results suggest a new approach for manipulation of inflammation as well as tumor cell invasion by targeting this novel signaling pathway.

Essential role of protein kinase C ζ in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP

PubMed Central

Kuribayashi, Kageaki; Nakamura, Kiminori; Tanaka, Maki; Sato, Tsutomu; Kato, Junji; Sasaki, Katsunori; Takimoto, Rishu; Kogawa, Katsuhisa; Terui, Takeshi; Takayama, Tetsuji; Onuma, Takayuki; Matsunaga, Takuya; Niitsu, Yoshiro

2007-01-01

Under various pathological conditions, including infection, malignancy, and autoimmune diseases, tissues are incessantly exposed to reactive oxygen species produced by infiltrating inflammatory cells. We show augmentation of motility associated with morphological changes of human squamous carcinoma SASH1 cells, human peripheral monocytes (hPMs), and murine macrophage-like cell line J774.1 by superoxide stimulation. We also disclose that motility of hPMs and J774.1 induced by a chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) was inhibited by superoxide dismutase or N-acetylcystein, indicating stimulation of motility by superoxide generated by fMLP stimulation. In these cells, protein kinase C (PKC) ζ was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation. These events were inhibited by dominant-negative PKCζ in SASH1 cells, myristoylated PKCζ peptides in hPMs and J774.1, or a specific inhibitor of RhoGTPase in SASH1, hPMs, and J774.1. These results suggest a new approach for manipulation of inflammation as well as tumor cell invasion by targeting this novel signaling pathway. PMID:17389234

Neutrophil formyl-peptide receptors. Relationship to peptide-induced responses and emphysema.

PubMed

Stockley, R A; Grant, R A; Llewellyn-Jones, C G; Hill, S L; Burnett, D

1994-02-01

A reproducible assay was established to assess the number of formyl-peptide receptors expressed on the surface of human polymorphonuclear leukocytes (PMN). Using this assay the number of receptors was shown to demonstrate wide within- and between-subject variability. However, the receptor numbers were related to the chemotactic response (r = 0.572) and degranulation response (r = 0.512) to the peptide formyl-methionyl-leucyl-phenylalanine. Subsequent studies showed increased receptor numbers on PMN from patients with emphysema (median, 459 x 10(3)/cell; range, 207 to 1,080) as compared with age-matched control subjects (median, 288; range, 168 to 519; p < 0.02), which may explain the increased chemotactic response of the PMN to formyl peptides. This difference was not observed in patients with bronchiectasis, suggesting that the increased receptor number is a feature of emphysema. Furthermore, the increase was largely a feature of smokers with emphysema (median, 463; range, 362 to 1,080), whereas age-matched smokers without emphysema had lower numbers of receptors (p < 0.001; median, 332; range, 243 to 411). This observation suggests a mechanism that may explain the susceptibility of some smokers to the development of emphysema.

Bacteria of leg atheromatous arteries responsible for inflammation.

PubMed

Olszewski, Waldemar Lech; Rutkowska, Joanna; Moscicka-Wesolowska, Maria; Swoboda-Kopec, Ewa; Stelmach, Ewa; Zaleska, Marzanna; Zagozda, Malgorzata

2016-09-01

Ischaemia of the lower limbs is frequently followed by inflammation and, in advanced cases, necrosis of peripheral tissues. Whether this is caused by arterial hypoperfusion only or by the presence of bacteria in the arterial walI as well remains unclear. The aim of the study was to prove the presence and source of bacteria in arterial specimens and evaluate their chemotactic properties resulting in the formation of periarterial cellular infiltrates. Bacterial culture and testing for 16sRNA were performed in fragments of popliteal artery harvested from amputated limbs. Carotid artery plaques served as controls. Fragments of arteries were transplanted into scid mice to evaluate their chemotactic activity for macrophages. a) higher prevalence of isolates and 16sRNA in atherosclerotic popliteal than carotid arteries, b) high density of plaque and periarterial infiltrates and mRNA level for pro-inflammatory cytokines in popliteal arteries, c) prevalent microbes were Staphylococcus aureus, S. epidermidis and Enterococci, d) foot skin and arterial bacterial phenotypes and DNA revealed evident similarities, and e) more intensive mouse macrophage accumulation in popliteal than carotid implants into scid mice. The presence of bacteria in the lower limb arterial wall was documented. They may predispose to inflammation secondary to ischaemic changes.

Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay.

PubMed

Bromberek, B A; Enever, P A J; Shreiber, D I; Caldwell, M D; Tranquillo, R T

2002-05-01

Rat dermal fibroblasts were dispersed initially in the outer shell of a fibrin gel sphere, while the inner core either was devoid of cells or contained peritoneal exudate cells (primarily macrophages), thereby mimicking the inflammatory phase of wound healing. The fibroblasts compacted floating fibrin microspheres over time. In the absence of macrophages, the initial distribution of fibroblasts (only in the shell) induced circumferential alignment of fibrin fibrils via compaction of the shell relative to the core. The aligned fibrils created a contact guidance field, which was manifested by strong circumferential alignment of the fibroblasts. However, in the presence of macrophages, the fibroblasts exhibited more radial alignment despite the simultaneous contact guidance field in the circumferential direction associated with compaction. This was attributed to a chemotactic gradient emanating from the core due to a putative factor(s) released by the macrophages. The presence of a radial chemotactic stimulus was supported by the finding of even greater radial alignment when fibrin microspheres were embedded in an agarose-fibrin gel that abolished compaction and consequently the contact guidance field. Our assay permits the simulation of tissue morphogenetic processes that involve cell guidance phenomena and tractional restructuring of the extracellular matrix.

Intracellular calcium rise is not a necessary step for the stimulated actin polymerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yassin, R.

1986-03-01

Stimulation of rabbit peritoneal neutrophils by many chemotactic (formyl Methionyl-Leucyl-Phenylalanine (fMLP), Leukotriene B/sub 4/ (LTB/sub 4/)) and non-chemotactic (phorbol 12-myristate, 13-acetate (PMA), platelet activating factor (PAF), and the calcium ionophore A23187) factors produces rapid and dose dependent increases in the amount of actin associated with the cytoskeleton. The stimulated increase in cytoskeletal actin does not appear to require a rise in the intracellular concentration of free calcium. The increase in cytoskeletal actin produced by A23187 is transient and does not depend on the presence of calcium in the suspending medium. In the presence of extracellular calcium, the effect of themore » ionophore is biphasic with respect to concentration. The increases in actin association with cytoskeletal produced by fMLP, LTB/sub 4/, and A23187 but not by PMA, are inhibited by hyperosmolarity and pertussis toxin pretreatment. On the other hand, the addition of hyperosmolarity or pertussis toxin has small effect on the rise in the intracellular calcium produced by A23187. The results presented here suggest that an increase in the intracellular concentration of free calcium is not necessary for the stimulated increases in cytoskeletal actin.« less

Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System.

PubMed

Barbieri, Federica; Thellung, Stefano; Würth, Roberto; Gatto, Federico; Corsaro, Alessandro; Villa, Valentina; Nizzari, Mario; Albertelli, Manuela; Ferone, Diego; Florio, Tullio

2014-01-01

Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas.

PREFACE: International Conference on Quantum Simulators and Design, Hiroshima, Japan, 3 6 December 2006

NASA Astrophysics Data System (ADS)

Akai, Hisazumi; Oguchi, Tamio

2007-09-01

This special issue of Journal of Physics: Condensed Matter comprises selected papers from the 1st International Conference on Quantum Simulators and Design (QSD2006) held in Hiroshima, Japan, 3-6 December 2006. This conference was organized under the auspices of the Development of New Quantum Simulators and Quantum Design Grant-in-Aid for Scientific Research on Priority Areas, Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and Hiroshima University Quantum design is a computational approach to the development of new materials with specified properties and functionalities. The basic ingredient is the use of quantum simulations to design a material that meets a given specification of properties and functionalities. For this to be successful, the quantum simulation should be highly reliable and be applicable to systems of realistic size. A central interest is, therefore, the development of new methods of quantum simulation and quantum design. This includes methods beyond the local density approximation of density functional theory (LDA), order-N methods, methods dealing with excitations and reactions, and so on, as well as the application of these methods to the design of new materials and devices. The field of quantum design has developed rapidly in the past few years and this conference provides an international forum for experimental and theoretical researchers to exchange ideas. A total of 183 delegates from 8 countries participated in the conference. There were 18 invited talks, 16 oral presentations and 100 posters. There were many new ideas and we foresee dramatic progress in the coming years. The 2nd International Conference on Quantum Simulators and Design will be held in Tokyo, Japan, 31 May-3 June 2008.

Plastic Surgery Intervention with Down Syndrome Persons: Summary of a Conference.

ERIC Educational Resources Information Center

Exceptional Parent, 1983

1983-01-01

The article discusses the role of plastic surgery for persons with Down Syndrome, as considered in a recent conference. The functions of team plastic surgery, importance of intensive speech therapy, and the question of ultimate therapeutic value are among questions considered. (CL)

Best Practices in Online Conference Moderation

ERIC Educational Resources Information Center

De Schutter, Adrienne; Fahrni, Patricia; Rudolph, Jim

2004-01-01

Facilitation by a moderator is crucial to a purposeful and productive conference. The moderator keeps the session focused, and ensures that all participants receive feedback regarding their contributions to the discussion. These functions are particularly important in the otherwise impersonal context of online discussion. The current report…

Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

PubMed

Luker, Gary D

2002-04-01

The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

Thioredoxin induces Tregs to generate an immunotolerant tumor microenvironment in metastatic melanoma

PubMed Central

Wang, Xiaogang; Dong, Haisheng; Li, Qi; Li, Yingxian; Hong, An

2015-01-01

Metastatic melanoma is a highly aggressive cancer that is very difficult to treat. Additionally, the antitumor immune reaction of melanoma is still unclear. Here we demonstrate an association between the expression and secretion of the antioxidant protein thioredoxin (TRX) and increasing tumor stage and metastasis in melanoma. To elucidate the role of TRX in melanoma, we assessed the correlation of TRX expression with different disease parameters in melanoma. We also examined the in vitro and in vivo effects of modulating TRX levels in melanoma cells using various methods of TRX depletion and augmentation. We further explored the effects of TRX on the cytokine milieu and the ability of TRX to regulate the proportion and specific activities of T-cell populations. We demonstrate that TRX expression correlates with Treg representation in clinical samples and, that modulation of TRX influences the induction of Tregs and the generation of an immunotolerant cytokine profile in mouse serum. Using a murine metastatic melanoma model, we identified a tumor immunoevasion mechanism whereby melanoma cell-secreted TRX enhances Treg infiltration. TRX displays chemotactic effects in recruiting Tregs, stimulates the conversion of conventional T cells to Tregs, and confers survival advantage to Tregs in the tumor microenvironment. In turn, this increase of Tregs generates immunotolerance in tissues and therefore decreases antitumor immune reactions. These results elucidate a mechanism by which TRX promotes metastatic melanoma in part through Treg recruitment to inhibit T-cell antitumor effects and suggest that TRX antibody may be useful in the clinic as a therapy against melanoma. PMID:26405597

77 FR 18798 - President's Council of Advisors on Science and Technology (PCAST)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... on Science and Technology (PCAST), and describes the functions of the Council. Notice of this meeting... purpose of this conference call is to discuss PCAST's Advanced Manufacturing Partnership report. DATES... the conference call, PCAST will discuss its Advanced Manufacturing Partnership report. Additional...

2012 Gordon Research Conference on Microbial Stress Response, Schedule and Speaker/Poster Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donohue, Timothy J.

2012-07-20

The Gordon Research Conference on Microbial Stress Response was held at Mount Holyoke College, South Hadley, Massachusetts, July 15-20, 2012. The Conference was well-attended with 180 participants. The 2012 Microbial Stress Responses Gordon Research Conference will provide a forum for the open reporting of recent discoveries on the diverse mechanisms employed by microbes to respond to stress. Approaches range from analysis at the molecular level (how are signals perceived and transmitted to change gene expression or function) to cellular and microbial community responses. Attached is a copy of the formal schedule and speaker program and the poster program.

PREFACE: Proceedings of the 2nd International Conference on Quantum Simulators and Design (Tokyo, Japan, 31 May-3 June 2008) Proceedings of the 2nd International Conference on Quantum Simulators and Design (Tokyo, Japan, 31 May-3 June 2008)

NASA Astrophysics Data System (ADS)

Akai, Hisazumi; Tsuneyuki, Shinji

2009-02-01

This special issue of Journal of Physics: Condensed Matter comprises selected papers from the proceedings of the 2nd International Conference on Quantum Simulators and Design (QSD2008) held in Tokyo, Japan, between 31 May and 3 June 2008. This conference was organized under the auspices of the Development of New Quantum Simulators and Quantum Design Grant-in-Aid for Scientific Research on Priority Areas, Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). The conference focused on the development of first principles electronic structure calculations and their applications. The aim was to provide an opportunity for discussion on the progress in computational materials design and, in particular, the development of quantum simulators and quantum design. Computational materials design is a computational approach to the development of new materials. The essential ingredient is the use of quantum simulators to design a material that meets a given specification of properties and functionalities. For this to be successful, the quantum simulator should be very reliable and be applicable to systems of realistic size. During the conference, new methods of quantum simulation and quantum design were discussed including methods beyond the local density approximation of density functional theory, order-N methods, methods dealing with excitations and reactions, and the application of these methods to the design of novel materials, devices and systems. The conference provided an international forum for experimental and theoretical researchers to exchange ideas. A total of 220 delegates from eight countries participated in the conference. There were 13 invited talks, ten oral presentations and 120 posters. The 3rd International Conference on Quantum Simulators and Design will be held in Germany in the autumn of 2011.

Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock

PubMed Central

Volk, Paige; Moreland, Jessica G.; Dunnwald, Martine

2016-01-01

Interferon Regulatory Factor (IRF) 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production. PMID:27035130

An Epoxyisoprostane is a Major Regulator of Endothelial Cell Function

PubMed Central

Zhong, Wei; Springstead, James R.; Al-Mubarak, Ramea; Lee, Sangderk; Li, Rongsong; Emert, Benjamin; Berliner, Judith A.; Jung, Michael E.

2014-01-01

The goal of these studies was to determine the effect of 5,6-epoxyisoprostane, EI, on human aortic endothelial cells (HAEC). EI can form as a phospholipase product of 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine, PEIPC, a pro-inflammatory molecule that accumulates in sites of inflammation where phospholipases are also increased. To determine the effect of EI on HAEC, we synthesized several stereoisomers of EI using a convergent approach from the individual optically pure building blocks, the epoxyaldehydes 5 and 6 and the bromoenones 14 and 16. The desired stereoisomer of EI can be prepared from these materials in only six operations and thus large amounts of the product can be obtained. The trans/trans isomers had the most potent activity, suggesting specificity in the interaction of EI with the cell surface. EI has potent anti-inflammatory effects in HAEC. EI strongly inhibits the production of MCP-1, a major monocyte chemotactic factor, and either decreases or minimally increases the levels of ten pro-inflammatory molecules increased by PEIPC. EI also strongly downregulates the inflammatory effects of IL-1β, a major inflammatory cytokine. Thus EI, a hydrolytic product of PEIPC, has potent anti-inflammatory function. PMID:24117045

Increased endothelial progenitor cell circulation and VEGF production in a rat model of noise-induced hearing loss.

PubMed

Yang, Dong; Zhou, Huifang; Zhang, Jianning; Liu, Li

2015-06-01

The vascular endothelial growth factor (VEGF)-mediated mechanism of endothelial progenitor cell (EPC) mobilization, migration, and differentiation may occur in response to noise-induced acoustic trauma of the cochlea, leading to the protection of cochlear function. The purpose of this study was to analyze changes in the cochlear vessel under an intensive noise environment. Sixty male Sprague-Dawley rats were randomly divided into six groups. Acoustic trauma was induced by 120 dB SPL white noise for 4 h. Auditory function was evaluated by the auditory brainstem response threshold. Morphological changes of the cochleae, the expression of VEGF, and the circulation of EPCs in the peripheral blood were studied by immunohistochemistry, Western blotting analysis, scanning electron microscopy, and flow cytometry. Vascular recovery of the cochlea began after noise exposure. The change in the number of EPCs was consistent with the expression of VEGF at different time points after noise exposure. We propose that VEGF evokes specific permeable and chemotactic effects on the vascular endothelial cells. These effects can mobilize EPCs into the peripheral blood, leading the EPCs to target damaged sites and to exert a neoangiogenic effect.

Downstream-of-FGFR Is a Fibroblast Growth Factor-Specific Scaffolding Protein and Recruits Corkscrew upon Receptor Activation

PubMed Central

Petit, Valérie; Nussbaumer, Ute; Dossenbach, Caroline; Affolter, Markus

2004-01-01

Fibroblast growth factor (FGF) receptor (FGFR) signaling controls the migration of glial, mesodermal, and tracheal cells in Drosophila melanogaster. Little is known about the molecular events linking receptor activation to cytoskeletal rearrangements during cell migration. We have performed a functional characterization of Downstream-of-FGFR (Dof), a putative adapter protein that acts specifically in FGFR signal transduction in Drosophila. By combining reverse genetic, cell culture, and biochemical approaches, we demonstrate that Dof is a specific substrate for the two Drosophila FGFRs. After defining a minimal Dof rescue protein, we identify two regions important for Dof function in mesodermal and tracheal cell migration. The N-terminal 484 amino acids are strictly required for the interaction of Dof with the FGFRs. Upon receptor activation, tyrosine residue 515 becomes phosphorylated and recruits the phosphatase Corkscrew (Csw). Csw recruitment represents an essential step in FGF-induced cell migration and in the activation of the Ras/MAPK pathway. However, our results also indicate that the activation of Ras is not sufficient to activate the migration machinery in tracheal and mesodermal cells. Additional proteins binding either to the FGFRs, to Dof, or to Csw appear to be crucial for a chemotactic response. PMID:15082772

Downstream-of-FGFR is a fibroblast growth factor-specific scaffolding protein and recruits Corkscrew upon receptor activation.

PubMed

Petit, Valérie; Nussbaumer, Ute; Dossenbach, Caroline; Affolter, Markus

2004-05-01

Fibroblast growth factor (FGF) receptor (FGFR) signaling controls the migration of glial, mesodermal, and tracheal cells in Drosophila melanogaster. Little is known about the molecular events linking receptor activation to cytoskeletal rearrangements during cell migration. We have performed a functional characterization of Downstream-of-FGFR (Dof), a putative adapter protein that acts specifically in FGFR signal transduction in Drosophila. By combining reverse genetic, cell culture, and biochemical approaches, we demonstrate that Dof is a specific substrate for the two Drosophila FGFRs. After defining a minimal Dof rescue protein, we identify two regions important for Dof function in mesodermal and tracheal cell migration. The N-terminal 484 amino acids are strictly required for the interaction of Dof with the FGFRs. Upon receptor activation, tyrosine residue 515 becomes phosphorylated and recruits the phosphatase Corkscrew (Csw). Csw recruitment represents an essential step in FGF-induced cell migration and in the activation of the Ras/MAPK pathway. However, our results also indicate that the activation of Ras is not sufficient to activate the migration machinery in tracheal and mesodermal cells. Additional proteins binding either to the FGFRs, to Dof, or to Csw appear to be crucial for a chemotactic response.

Chemotaxis and adherence to fungal surfaces are key components of the behavioral response of Burkholderia terrae BS001 to two selected soil fungi.

PubMed

Haq, Irshad Ul; Calixto, Renata Oliveira da Rocha; Yang, Pu; Dos Santos, Giulia Maria Pires; Barreto-Bergter, Eliana; van Elsas, Jan Dirk

2016-11-01

Burkholderia terrae BS001 has previously been proposed to be a 'generalist' associate of soil fungi, but its strategies of interaction have been largely ignored. Here, we studied the chemotactic behavior of B. terrae BS001 towards Lyophyllum sp. strain Karsten and Trichoderma asperellum 302 and the role of fungal surface molecules in their physical interaction with the bacteria. To assess the involvement of the type 3 secretion system (T3SS), wild-type strain BS001 and T3SS mutant strain BS001-ΔsctD were used in the experiments. First, the two fungi showed divergent behavior when confronted with B. terrae BS001 on soil extract agar medium. Lyophyllum sp. strain Karsten revealed slow growth towards the bacterium, whereas T. asperellum 302 grew avidly over it. Both on soil extract and M9 agar, B. terrae BS001 and BS001-ΔsctD moved chemotactically towards the hyphae of both fungi, with a stronger response to Lyophyllum sp. strain Karsten than to T. asperellum 302. The presence of a progressively increasing glycerol level in the M9 agar enhanced the level of movement. Different oxalic acid concentrations exerted varied effects, with a significantly raised chemotactic response at lower, and a subdued response at higher concentrations. Testing of the adherence of B. terrae BS001 and BS001-ΔsctD to Lyophyllum sp. strain Karsten and to cell envelope-extracted ceramide monohexosides (CMHs) revealed that CMHs in both conidia and hyphae could bind strain BS001 cells. As BS001-ΔsctD adhered significantly less to the CMHs than BS001, the T3SS was presumed to have a role in the interaction. In contrast, such avid adherence was not detected with T. asperellum 302. Thus, B. terrae BS001 shows a behavior characterized by swimming towards Lyophyllum sp. strain Karsten and T. asperellum 302 and attachment to the CMH moiety in the cell envelope, in particular of the former. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reconstitution of a physical complex between the N-formyl chemotactic peptide receptor and G protein. Inhibition by pertussis toxin-catalyzed ADP ribosylation.

PubMed

Bommakanti, R K; Bokoch, G M; Tolley, J O; Schreiber, R E; Siemsen, D W; Klotz, K N; Jesaitis, A J

1992-04-15

Photoaffinity-labeled N-formyl chemotactic peptide receptors from human neutrophils solubilized in octyl glucoside exhibit two forms upon sucrose density gradient sedimentation, with apparent sedimentation coefficients of approximately 4 and 7 S. The 7 S form can be converted to the 4 S form by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) with an EC50 of approximately 20 nM, suggesting that the 7 S form may represent a physical complex of the receptor with endogenous G protein (Jesaitis, A. J., Tolley, J. O., Bokoch, G. M., and Allen, R. A. (1989) J. Cell Biol. 109, 2783-2790). To probe the nature of the 7 S form, we reconstituted the 7 S form from the 4 S form by adding purified G protein. The 4 S form, obtained by solubilizing GTP gamma S-treated neutrophil plasma membranes, was incubated with purified (greater than 95%) Gi protein from bovine brain (containing both Gi alpha 1 and Gi alpha 2) or with neutrophil G protein (Gn), and formation of the 7 S complex was analyzed on sucrose density gradients. The EC50 of 7 S complex formation induced by the two G proteins was 70 +/- 25 and 170 +/- 40 nM for Gn and Gi, respectively. No complexation was measurable when bovine transducin (Gt) was used up to 30 times the EC50 for Gn. The EC50 for Gi was the same for receptors, obtained from formyl peptide-stimulated or unstimulated cells. The addition of 10 microM GTP gamma S to the reconstituted 7 S complex caused a complete revision of the receptor to the 4 S form, and anti-Gi peptide antisera immunosedimented the 7 S form. ADP-ribosylation of Gi prevented formation of the 7 S form even at 20 times the concentration of unribosylated Gi normally used to attain 50% conversion to the 7 S form. These observations suggest that the 7 S species is a physical complex containing N-formyl chemotactic peptide receptor and G protein.

Arts Education Policy Lessons Learned from the Southeastern College Art Conference

ERIC Educational Resources Information Center

Brewer, Thomas M.

2009-01-01

This article provides functional, moderate, and constructive arts education policy lessons drawn from the development of two Southeastern College Art Conference (SECAC) visual arts education policy statements over the past fifteen years. These lessons can help formulate action-oriented school, district, state, and national pre-kindergarten-20…

On the Conference as an Integrating Mechanism.

ERIC Educational Resources Information Center

Feldman, Wendy; Johnson, J. David

Due to their increasing complexity, modern organizations require more effective integrating mechanisms. The conference, which can be a very positive thing for an organization as it provides rewards for members while performing a crucial communication function for the whole, is one possible mechanism. Communication is not only an inherent part of…

Technology for Consumers: Proceedings of the RESNA International Conference (Toronto, Ontario, Canada, June 6-11, 1992).

ERIC Educational Resources Information Center

Presperin, Jessica J., Ed.

This proceedings document contains approximately 250 papers and posters presented at a conference on the advancement of rehabilitation and assistive technology. Individual sessions focused on the following topics: quantitative functional evaluation, upper limb and therapeutic stimulation, human-computer interface developments, information…

A maize caffeoyl-CoA O-methyltransferase gene confers quantitative resistance to multiple pathogens

USDA-ARS?s Scientific Manuscript database

Alleles that confer multiple disease resistance (MDR) are valuable in crop improvement though molecular mechanisms underlying their functions remain largely unknown. A QTL, qMdr9.02, associated with resistance to three important foliar maize diseases, southern leaf blight (SLB), gray leaf spot (GLS)...

Curriculum and Instruction: Reactions.

ERIC Educational Resources Information Center

Passow, A. Harry

The papers presented at this conference review current research on effective educational practices for low-achieving students and identify those that might be applied to programs funded under Chapter 1 of the Education Consolidation and Improvement Act of 1981. A function assumed by several conference participants was to act as reactor to papers…

Academy of Human Resource Development Conference Proceedings (San Antonio, Texas, March 3-6, 1994).

ERIC Educational Resources Information Center

Brooks, Annie, Ed.; Watkins, Karen, Ed.

This document contains the following 26 papers presented at the first Academy of Human Resource Development (HRD) Conference: "Management as a Service to Internal Customers" (Antonioni); "Developing Texas State Agency Executives for the Learning Organizations" (Bales); "How Executive Businesswomen Develop and Function in…

Functional Body Composition and Related Aspects in Research on Obesity and Cachexia

PubMed Central

Müller, M.J.; Baracos, V.; Bosy-Westphal, A.; Dulloo, A.; Eckel, J.; Fearon, K.C.H.; Hall, K.D.; Pietrobelli, A.; Sørensen, T.I.A.; Speakman, J.; Trayhurn, P.; Visser, M.; Heymsfield, S.B.

2014-01-01

The 12th Stock Conference addressed body composition and related functions in two extreme situations, obesity and cancer cachexia. The concept of “functional body composition” integrates body components into regulatory systems relating the mass of organs and tissues to corresponding in vivo functions and metabolic processes. This concept adds to an understanding of organ/tissue mass and function in the context of metabolic adaptations to weight change and disease. During weight gain and loss there are associated changes in individual body components while the relationships between organ and tissue mass are fixed. Thus, an understanding of weight regulation involves an examination of organ-tissue regulation rather than of individual organ mass. The between organ/tissue mass relationships are associated with and explained by cross-talk between organs and tissues mediated by cytokines, hormones, and metabolites that are coupled with changes in body weight, composition, and function as observed in obesity and cancer cachexia. In addition to established roles in intermediary metabolism, cell function and inflammation, organ-tissue cross-talk mediators are determinants of body composition and its’ change with weight gain and loss. The 12th Stock Conference supported Michael Stocks’ concept of gaining new insights by integrating research ideas from obesity and cancer cachexia. The conference presentations provide an in-depth understanding of body composition and metabolism. PMID:24835453

Clarifying CB2 receptor-dependent and independent effects of THC on human lung epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarafian, Theodore; Montes, Cindy; Harui, Airi

Marijuana smoking is associated with a number of abnormal findings in the lungs of habitual smokers. Previous studies revealed that {delta}{sup 9}-tetrahydrocannabinol (THC) caused mitochondrial injury in primary lung epithelial cells and in the cell line, A549 [Sarafian, T. A., Kouyoumjian, S., Khoshaghideh, F., Tashkin, D. P., and Roth, M. D. (2003). Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284, L298-306; Sarafian, T., Habib, N., Mao, J. T., Tsu, I. H., Yamamoto, M. L., Hsu, E., Tashkin, D. P., and Roth, M. D. (2005). Gene expression changes in human small airway epithelialmore » cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett 158, 95-107]. The role of cannabinoid receptors in this injury was unclear, as was the potential impact on cell function. In order to investigate these questions, A549 cells were engineered to over-express the type 2 cannabinoid receptor (CB2R) using a self-inactivating lentiviral vector. This transduction resulted in a 60-fold increase in CB2R mRNA relative to cells transduced with a control vector. Transduced cell lines were used to study the effects of THC on chemotactic activity and mitochondrial function. Chemotaxis in response to a 10% serum gradient was suppressed in a concentration-dependent manner by exposure to THC. CB2R-transduced cells exhibited less intrinsic chemotactic activity (p < 0.05) and were 80- to 100-fold more sensitive to the inhibitory effects of THC. Studies using SR144528, a selective CB2R antagonist, verified that these effects were mediated by the CB2R. Marijuana smoke extract, but not smoke extracts from tobacco or placebo marijuana cigarettes, reproduced these effects (p < 0.05). THC decreased ATP level and mitochondrial membrane potential ({psi}{sub m}) in both control and CB2R-transduced cells. However, these decreases did not play a significant role in chemotaxis inhibition since cyclosporine A, which protected against ATP loss, did not increase cell migration. Moreover, CB2R-transduced cells displayed higher {psi}{sub m} than did control cells. Since both {psi}{sub m} and chemotaxis are regulated by intracellular signaling, we investigated the effects of THC on the activation of multiple signaling pathways. Serum exposure activated several signaling events of which phosphorylation of I{kappa}B-{alpha} and JNK was regulated in a CB2R- and THC-dependent manner. We conclude that airway epithelial cells are sensitive to both CB2R-dependent and independent effects mediated by THC.« less

PREFACE: MRS International Materials Research Conference (IMRC-2008)

NASA Astrophysics Data System (ADS)

Wang, Zhanguo; Qiu, Yong; Li, Yongxiang

2009-03-01

This volume contains selected papers presented at the MRS International Materials Research Conference (IMRC-2008) held in Chongqing, China, 9-12 June 2008. IMRC-2008 included 9 symposia of A. Eco/Environmental Materials, B. Sustainable Energy Materials, C. Electronic Packaging Materials, D. Electronic Materials, E. Materials and Processes for Flat-panel Displays, F. Functional Ceramics, G. Transportation Materials, H. Magnesium and I. Biomaterials for Medical Applications. Nearly 1200 participants from 33 countries attended the conference, and the conference organizers received more than 700 papers. After the peer review processes, 555 papers were selected to be published in 9 Journals or proceedings, including J. of Materials Research (JMR), Rare Metal Materials and Engineering, J. of Univ. Science and Technology Beijing, Biomedical Materials: Materials for Tissue Engineering and Regenerative Medicine, Chinese Journal of Aeronautics, Materials Science Forum, and Journal of Physics: Conference Series. Among the 555 selected papers, 91 papers are published in this volume, and the topics mainly cover electronic matrials, processes for flat-panel displays and functional ceramics. The editors would like to give special thanks to the graduate students Liwu Jiang, Ming Li and Di He from Beihang University for their hard work compiling and typesetting each paper in this volume. Zhanguo Wang, Yong Qiu and Yongxiang Li Editors

Elastic Multi-scale Mechanisms: Computation and Biological Evolution.

PubMed

Diaz Ochoa, Juan G

2018-01-01

Explanations based on low-level interacting elements are valuable and powerful since they contribute to identify the key mechanisms of biological functions. However, many dynamic systems based on low-level interacting elements with unambiguous, finite, and complete information of initial states generate future states that cannot be predicted, implying an increase of complexity and open-ended evolution. Such systems are like Turing machines, that overlap with dynamical systems that cannot halt. We argue that organisms find halting conditions by distorting these mechanisms, creating conditions for a constant creativity that drives evolution. We introduce a modulus of elasticity to measure the changes in these mechanisms in response to changes in the computed environment. We test this concept in a population of predators and predated cells with chemotactic mechanisms and demonstrate how the selection of a given mechanism depends on the entire population. We finally explore this concept in different frameworks and postulate that the identification of predictive mechanisms is only successful with small elasticity modulus.

Excitation and Adaptation in Bacteria–a Model Signal Transduction System that Controls Taxis and Spatial Pattern Formation

PubMed Central

Othmer, Hans G.; Xin, Xiangrong; Xue, Chuan

2013-01-01

The machinery for transduction of chemotactic stimuli in the bacterium E. coli is one of the most completely characterized signal transduction systems, and because of its relative simplicity, quantitative analysis of this system is possible. Here we discuss models which reproduce many of the important behaviors of the system. The important characteristics of the signal transduction system are excitation and adaptation, and the latter implies that the transduction system can function as a “derivative sensor” with respect to the ligand concentration in that the DC component of a signal is ultimately ignored if it is not too large. This temporal sensing mechanism provides the bacterium with a memory of its passage through spatially- or temporally-varying signal fields, and adaptation is essential for successful chemotaxis. We also discuss some of the spatial patterns observed in populations and indicate how cell-level behavior can be embedded in population-level descriptions. PMID:23624608

A macrophage NBR1-MEKK3 complex triggers JNK-mediated adipose-tissue inflammation in obesity

PubMed Central

Hernandez, Eloy D.; Lee, Sang Jun; Kim, Ji Young; Duran, Angeles; Linares, Juan F.; Yajima, Tomoko; Müller, Timo D.; Tschöp, Matthias H.; Smith, Steven R.; Diaz-Meco, Maria T.; Moscat, Jorge

2014-01-01

SUMMARY The c-Jun NH(2)-terminal kinase (JNK) is a critical determinant of obesity-associated inflammation and glucose intolerance. The upstream mechanisms controlling this pathway are still unknown. Here we report that the levels of the PB1 domain-containing adapter NBR1 correlated with the expression of pro-inflammatory molecules in adipose tissue from human patients with metabolic syndrome, suggesting that NBR1 plays a key role in adipose-tissue inflammation. We also show that NBR1 inactivation in the myeloid compartment impairs the function, M1 polarization and chemotactic activity of macrophages, prevents inflammation of adipose tissue, and improves glucose tolerance in obese mice. Furthermore, we demonstrate that an interaction between the PB1 domains of NBR1 and the mitogen-activated kinase kinase 3 (MEKK3) enables the formation of a signaling complex required for the activation of JNK. Together these discoveries identify an NBR1-MEKK3 complex as a key regulator of JNK signaling and adipose-tissue inflammation in obesity. PMID:25043814

Laminar flow assisted anisotropic bacteria absorption for chemotaxis delivery of bacteria-attached microparticle

NASA Astrophysics Data System (ADS)

Huh, Keon; Oh, Darong; Son, Seok Young; Yoo, Hyung Jung; Song, Byeonghwa; Cho, Dong-il Dan; Seo, Jong-Mo; Kim, Sung Jae

2016-12-01

The concepts of microrobots has been drawn significant attentions recently since its unprecedented applicability in nanotechnology and biomedical field. Bacteria attached microparticles presented in this work are one of pioneering microrobot technology for self-propulsion or producing kinetic energy from ambient for their motions. Microfluidic device, especially utilizing laminar flow characteristics, were employed for anisotropic attachment of Salmonella typhimurium flagellated chemotactic bacteria to 30 um × 30 um and 50 um × 50 um microparticles that made of biodegradable polymer. Any toxic chemicals or harmful treatments were excluded during the attachment process and it finished within 100 s for the anisotropic attachment. The attachments were directly confirmed by fluorescent intensity changes and SEM visualization. Chemotaxis motions were tracked using aspartate and the maximum velocity of the bacteria-attached microrobot was measured to be 5 um/s which is comparable to prior state of art technologies. This reusable and scalable method could play a key role in chemotaxis delivery of functional microparticles such as drug delivery system.

Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

NASA Astrophysics Data System (ADS)

Koch, Alisa E.; Halloran, Margaret M.; Haskell, Catherine J.; Shah, Manisha R.; Polverini, Peter J.

1995-08-01

ENDOTHELIAL adhesion molecules facilitate the entry of leukocytes into inflamed tissues. This in turn promotes neovascularization, a process central to the progression of rheumatoid arthritis, tumour growth and wound repair1. Here we test the hypothesis that soluble endothelial adhesion molecules promote angiogenesis2á¤-4. Human recombinant soluble E-selectin and soluble vascular cell adhesion molecule-1 induced chemotaxis of human endothelial cells in vitro and were angiogenic in rat cornea. Soluble E-selectin acted on endothelial cells in part through a sialyl Lewis-X-dependent mechanism, while soluble vascular cell adhesion molecule-1 acted on endothelial cells in part through a very late antigen (VLA)-4 dependent mechanism. The chemotactic activity of rheumatoid synovial fluid for endothelial cells, and also its angiogenic activity, were blocked by antibodies to either soluble E-selectin or soluble vascular cell adhesion molecule-1. These results suggest a novel function for soluble endothelial adhesion molecules as mediators of angiogenesis.

Structuring effects of chemicals from the sea fan Phyllogorgia dilatata on benthic communities.

PubMed

Ribeiro, Felipe V; da Gama, Bernardo A P; Pereira, Renato C

2017-01-01

Despite advances in understanding the ecological functions of secondary metabolites from marine organisms, there has been little focus on the influence of chemically-defended species at the community level. Several compounds have been isolated from the gorgonian octocoral Phyllogorgia dilatata , a conspicuous species that forms dense canopies on rocky reefs of northern Rio de Janeiro State, Brazil. Manipulative experiments were performed to study: (1) the effects of live colonies of P. dilatata (physical presence and chemistry) on recruitment of sympatric benthic organisms; (2) the allelopathic effects of its chemicals on competitors; and (3) chemotactic responses of the non-indigenous brittle star, Ophiothela mirabilis . Early establishment of benthic species was influenced on substrates around live P. dilatata colonies and some effects could be attributed to the gorgonian's secondary metabolites . In addition, the gorgonian chemicals also exerted an allelopathic effect on the sympatric zoanthid Palythoa caribaeorum, and positive chemotaxis upon O. mirabilis . These results indicate multiple ecological roles of a chemically-defended gorgonian on settlement, sympatric competitors, and non-indigenous species.

CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface

PubMed Central

Achour, Lamia; Scott, Mark G.H.; Shirvani, Hamasseh; Thuret, Alain; Bismuth, Georges; Labbé-Jullié, Catherine; Marullo, Stefano

2009-01-01

The association of CD4, a glycoprotein involved in T cell development and antigen recognition, and CCR5, a chemotactic G protein-coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for the human immunodeficiency virus HIV. We observed that the vast majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relative low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration–dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cell distribution of CXCR4, the other HIV co-receptor. These results reveal a previously unappreciated role of CD4, which contributes to regulate CCR5 export to the plasma membrane. PMID:19064722

Prokaryotic expression and in vitro functional analysis of IL-1β and MCP-1 from guinea pig.

PubMed

Dirisala, Vijaya R; Jeevan, Amminikutty; Ly, Lan H; McMurray, David N

2013-06-01

The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector, and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes, and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases.

PREFACE: International Conference on Dynamics of Systems on the Nanoscale (DySoN 2012)

NASA Astrophysics Data System (ADS)

Solov'yov, Andrey V.

2013-06-01

Conference logo The Second International Conference 'Dynamics of Systems on the Nanoscale' (DySoN 2012) took place in Saint Petersburg, Russia between 30 September and 4 October 2012. The venue was the Courtyard by Marriott St Petersburg Vasilievsky Hotel, 2nd line of Vasilievsky Island 61/30A, 199178. The conference was organized by the Frankfurt Institute for Advanced Studies - Goethe University, A F Ioffe Physical-Technical Institute and Saint Petersburg State Polytechnic University. This DySoN conference has been built upon a series of International Symposia 'Atomic Cluster Collisions: structure and dynamics from the nuclear to the biological scale' (ISACC 2003, ISACC 2007, ISACC 2008, ISACC 2009 and ISACC 2011). During these meetings it has become clear that there is a need for an interdisciplinary conference covering a broader range of topics than just atomic cluster collisions, related to the Dynamics of Systems on a Nanoscale. Therefore, in 2010 it was decided to launch a new conference series under the title 'Dynamics of Systems on the Nanoscale'. The first DySoN conference took place at the National Research Council, Rome, Italy in 2010. The DySoN 2012 is the second conference in this series. The DySoN 2012 Conference promoted the growth and exchange of interdisciplinary scientific information on the structure, formation and dynamics of animate and inanimate matter on the nanometer scale. There are many examples of complex many-body systems of micro- and nanometer scale size exhibiting unique features, properties and functions. These systems may have very different nature and origin, e.g. atomic and molecular clusters, nanoobjects, ensembles of nanoparticles, nanostructures, biomolecules, biomolecular and mesoscopic systems. A detailed understanding of the structure and dynamics of these systems on the nanometer scale is an important fundamental task, the solution of which is necessary in numerous applications of nano- and biotechnology, material science and medicine. Although mesoscopic, nano- and biomolecular systems differ in their nature and origin, a number of fundamental problems are common to all of them: what are the underlying principles of self-organization and self-assembly of matter on the micro- and nanoscale? Are these principles classical or quantum? How does function emerge on the nano- and the mesoscale in systems of different origin? What criteria govern the stability of these systems? How do their properties change as a function of size and composition? How are their properties altered by their environment? Seeking answers to these questions is at the core of a new interdisciplinary field that lies at the intersection of physics, chemistry and biology, a field called Meso-Bio-Nano (MBN) Science. Both experimental and theoretical aspects of the mentioned problems were discussed at the DySoN 2012 Conference. Particular attention was devoted to dynamical phenomena and many-body effects taking place in various MBN systems, which include problems of structure formation, fusion and fission, collision and fragmentation, collective electron excitations, reactivity, nanoscale phase transitions, nanoscale insights into biodamage, channeling phenomena and many more. This volume is a collection of the contributions received from the participants of the DySoN 2012 Conference. It provides an overview of the topics, new results and ideas that have been discussed at the conference. I would like to thank all the authors of these proceedings, as well as all the participants of the conference for making it so successful. The third DySoN Conference will be held in Edinburgh in May 2014. A V Solov'yov Frankfurt Institute for Advanced Studies, Ruth-Moufang Str. 1, 60438, Frankfurt am Main, Germany On leave from A F Ioffe Physical-Technical Institute, Polytechnicheskaya 26, 194021, St. Petersburg, Russia E-mail: solovyov@fias.uni-frankfurt.de The PDF contains further information about the conference. Conference photograph Picture

III International Conference on Laser and Plasma Researches and Technologies

NASA Astrophysics Data System (ADS)

2017-12-01

A.P. Kuznetsov and S.V. Genisaretskaya III Conference on Plasma and Laser Research and Technologies took place on January 24th until January 27th, 2017 at the National Research Nuclear University "MEPhI" (NRNU MEPhI). The Conference was organized by the Institute for Laser and Plasma Technologies and was supported by the Competitiveness Program of NRNU MEPhI. The conference program consisted of nine sections: • Laser physics and its application • Plasma physics and its application • Laser, plasma and radiation technologies in industry • Physics of extreme light fields • Controlled thermonuclear fusion • Modern problems of theoretical physics • Challenges in physics of solid state, functional materials and nanosystems • Particle accelerators and radiation technologies • Modern trends of quantum metrology. The conference is based on scientific fields as follows: • Laser, plasma and radiation technologies in industry, energetic, medicine; • Photonics, quantum metrology, optical information processing; • New functional materials, metamaterials, “smart” alloys and quantum systems; • Ultrahigh optical fields, high-power lasers, Mega Science facilities; • High-temperature plasma physics, environmentally-friendly energetic based on controlled thermonuclear fusion; • Spectroscopic synchrotron, neutron, laser research methods, quantum mechanical calculation and computer modelling of condensed media and nanostructures. More than 250 specialists took part in the Conference. They represented leading Russian scientific research centers and universities (National Research Centre "Kurchatov Institute", A.M. Prokhorov General Physics Institute, P.N. Lebedev Physical Institute, Troitsk Institute for Innovation and Fusion Research, Joint Institute for Nuclear Research, Moscow Institute of Physics and Tecnology and others) and leading scientific centers and universities from Germany, France, USA, Canada, Japan. We would like to thank heartily all of the speakers, participants, organizing and program committee members for their contribution to the conference.

Behaviour change interventions to influence antimicrobial prescribing: a cross-sectional analysis of reports from UK state-of-the-art scientific conferences.

PubMed

Rawson, T M; Moore, L S P; Tivey, A M; Tsao, A; Gilchrist, M; Charani, E; Holmes, A H

2017-01-01

To improve the quality of antimicrobial stewardship (AMS) interventions the application of behavioural sciences supported by multidisciplinary collaboration has been recommended. We analysed major UK scientific research conferences to investigate AMS behaviour change intervention reporting. Leading UK 2015 scientific conference abstracts for 30 clinical specialties were identified and interrogated. All AMS and/or antimicrobial resistance(AMR) abstracts were identified using validated search criteria. Abstracts were independently reviewed by four researchers with reported behavioural interventions classified using a behaviour change taxonomy. Conferences ran for 110 days with >57,000 delegates. 311/12,313(2.5%) AMS-AMR abstracts (oral and poster) were identified. 118/311(40%) were presented at the UK's infectious diseases/microbiology conference. 56/311(18%) AMS-AMR abstracts described behaviour change interventions. These were identified across 12/30(40%) conferences. The commonest abstract reporting behaviour change interventions were quality improvement projects [44/56 (79%)]. In total 71 unique behaviour change functions were identified. Policy categories; "guidelines" (16/71) and "service provision" (11/71) were the most frequently reported. Intervention functions; "education" (6/71), "persuasion" (7/71), and "enablement" (9/71) were also common. Only infection and primary care conferences reported studies that contained multiple behaviour change interventions. The remaining 10 specialties tended to report a narrow range of interventions focusing on "guidelines" and "enablement". Despite the benefits of behaviour change interventions on antimicrobial prescribing, very few AMS-AMR studies reported implementing them in 2015. AMS interventions must focus on promoting behaviour change towards antimicrobial prescribing. Greater focus must be placed on non-infection specialties to engage with the issue of behaviour change towards antimicrobial use.

Education in Asia and the Pacific: Reviews, Reports and Notes. Number 23.

ERIC Educational Resources Information Center

Education in Asia and the Pacific: Reviews, Reports and Notes, 1986

1986-01-01

The first article in this annual compilation ("Review of an International Conference on the University in the Future World," by Ransoo Kim) describes an international conference of Christian universities, held in May, 1985 at Yonsei University, to review the functions, problems, and missions of universities from a global perspective. Universities…

Designing Jobs for Handicapped Workers. Conference Proceedings (Chicago, Illinois, December 1985).

ERIC Educational Resources Information Center

Greenwood, Reed, Ed.

In these conference proceedings on employing workers with physical disabilities, an overview describes the scope of the need for modifying worksites. It emphasizes the need for a functional evaluation of the person's capabilities and an understanding of individual differences which must be considered in the design of assistive devices. Also…

PREFACE: VI Scientific Technical Conference on "Low-temperature plasma during the deposition of functional coatings"

NASA Astrophysics Data System (ADS)

2014-11-01

The VI Republican Scientific Technical Conference "Low-temperature plasma during the deposition of functional coatings" took place from 4 to 7 November 2014 at the Academy of Sciences of the Republic of Tatarstan and the Kazan Federal University. The conference was chaired by a Member of the Academy of Sciences of the Republic of Tatarstan Nail Kashapov -Professor, Doctor of Technical Sciences- a member of the Scientific and Technical Council of the Ministry of Economy of the Republic of Tatarstan. At the conference, the participants discussed a wide range of issues affecting the theoretical and computational aspects of research problems in the physics and technology of low-temperature plasma. A series of works were devoted to the study of thin films obtained by low-temperature plasma. This year work dedicated to the related field of heat mass transfer in multiphase media and low-temperature plasma was also presented. Of special interest were reports on the exploration of gas discharges with liquid electrolytic electrotrodes and the study of dusty plasmas. Kashapov Nail, D.Sc., Professor (Kazan Federal University)

Chemotaxis of nurse shark leukocytes.

PubMed

Obenauf, S D; Smith, S H

1985-01-01

Studies were conducted to determine the ability of leukocytes from the nurse shark to migrate in an in vitro micropore filter chemotaxis assay and to determine optimal assay conditions and suitable attractants for such an assay. A migratory response was seen with several attractants: activated rat serum, activated shark plasma, and a pool of shark complement components. Only the response to activated rat serum was chemotactic, as determined by the checkerboard assay.

Platelet-Derived Growth Factor in the Ovarian Follicle Attracts the Stromal Cells of the Fallopian Tube Fimbriae

PubMed Central

Chen, Chiu-Hua; Hsu, Che-Fang; Huang, Rui-Len; Ding, Dah-Ching; Chu, Tang-Yuan

2016-01-01

During human ovulation, the fallopian tube fimbriae must move to the ovulation site to catch the oocyte. As the tissue-of-origin of the majority of ovarian high-grade serous carcinoma (HGSC), the fallopian tube fimbriae carrying a precursor cancer lesion may also approach the ovulatory site for metastasis. We hypothesize that platelet-derived growth factor (PDGF) in mature follicle fluid (FF) attracts the migration of PDGFR-expressing fimbriae toward the ovulating follicle. We observed that more PDGFR-β was expressed in the distal part than in the proximal parts of the fallopian tube, particularly in stromal cells in the lamina propria. The stromal cells, but not the epithelial cells, from normal fimbriae and fallopian tube HGSC were highly chemotactic to mature FF. The chemotactic activities were positively correlated with PDGF-BB and estradiol levels in FF and were abolished by a blocking antibody of PDGFR-β and by tyrosine kinase inhibitor imatinib. When PDGF-BB/AB was depleted from the FF, more than 80% of chemotaxis activities were diminished. This study suggests an ovarian follicle-directed and PDGF-dependent attraction of fallopian tube fimbriae before ovulation. The same mechanism may also be crucial for the ovarian homing of HGSC, which largely originates in the fimbriae. PMID:27379403

Inferring the Chemotactic Strategy of P. putida and E. coli Using Modified Kramers-Moyal Coefficients

PubMed Central

Hintsche, Marius; Beta, Carsten; Stark, Holger

2017-01-01

Many bacteria perform a run-and-tumble random walk to explore their surrounding and to perform chemotaxis. In this article we present a novel method to infer the relevant parameters of bacterial motion from experimental trajectories including the tumbling events. We introduce a stochastic model for the orientation angle, where a shot-noise process initiates tumbles, and analytically calculate conditional moments, reminiscent of Kramers-Moyal coefficients. Matching them with the moments calculated from experimental trajectories of the bacteria E. coli and Pseudomonas putida, we are able to infer their respective tumble rates, the rotational diffusion constants, and the distributions of tumble angles in good agreement with results from conventional tumble recognizers. We also define a novel tumble recognizer, which explicitly quantifies the error in recognizing tumbles. In the presence of a chemical gradient we condition the moments on the bacterial direction of motion and thereby explore the chemotaxis strategy. For both bacteria we recover and quantify the classical chemotactic strategy, where the tumble rate is smallest along the chemical gradient. In addition, for E. coli we detect some cells, which bias their mean tumble angle towards smaller values. Our findings are supported by a scaling analysis of appropriate ratios of conditional moments, which are directly calculated from experimental data. PMID:28114420

Anethole and eugenol reduce in vitro and in vivo leukocyte migration induced by fMLP, LTB4, and carrageenan.

PubMed

Estevão-Silva, Camila Fernanda; Kummer, Raquel; Fachini-Queiroz, Fernanda Carolina; Grespan, Renata; Nogueira de Melo, Gessilda Alcântara; Baroni, Silmara; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

2014-07-01

The aim of this study was to investigate the effect of anethole (AN) and eugenol (EUG) on leukocyte migration using in vitro chemotaxis and in situ microcirculation assays. BALB/c mice were used for the in vitro chemotaxis assay, and Wistar rats for the in situ microcirculation assay. We evaluated (a) the in vitro leukocyte migration in response to chemotactic factors (formyl-methionyl-leucyl-phenylalanine [fMLP] and leukotriene B4 [LTB4]) and (b) the rolling, adhesion, and migration of leukocytes induced by an injection of carrageenan (100 µg/cavity) into the scrotum of the animal. In the in vitro chemotaxis assay, AN and EUG at doses of 1, 3, 9, and 27 µg/ml significantly inhibited leukocyte migration when stimulated by the chemotactic agents fMLP and LTB4. In the in situ microcirculation assay, AN at doses of 125 and 250 mg/kg and EUG at a dose of 250 mg/kg significantly decreased the number of leukocytes that rolled, adhered, and migrated to perivascular tissue. The results indicate that AN and EUG exert inhibitory effects on leukocyte migration, highlighting their possible use to diminish excessive leukocyte migration in the inflammatory process.

Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1

PubMed Central

Jo, Deog-Yeon; Rafii, Shahin; Hamada, Tsuneyoshi; Moore, Malcolm A.S.

2000-01-01

Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo. PMID:10619866

Thermal impulse response and the temperature preference of Escherichia coli

NASA Astrophysics Data System (ADS)

Ryu, William

2010-03-01

From a broad perspective, exposure to environmental temperature changes is a universal condition of living organisms. Escherichia coli is a powerful model system to study how a biochemical network measures and processes thermal information to produce adaptive changes in behavior. E. coli performs thermotaxis, directing its movements to a preferred temperature in spatial thermal gradients. How does the system perform thermotaxis? Where biologically is this analog value of thermal preference stored? Previous studies using populations of cells have shown that E.coli accumulate in spatial thermal gradients, but these experiments did not cleanly separate thermal responses from chemotactic responses. Here we have isolated the thermal behavior by studying the thermal impulse response of single, tethered cells. The motor output of cells was measured in response to small, impulsive increases in temperature, delivered by an infrared laser, over a range of ambient temperature (23 to 43 degrees C). The thermal impulse response at temperatures < 31 degrees C is similar to the chemotactic impulse response: both follow a similar time course, share the same directionality, and show biphasic characteristics. At temperatures > 31 degrees C, some cells show an inverted response, switching from warm- to cold-seeking behavior. The fraction of inverted responses increases nonlinearly with temperature, switching steeply at the preferred temperature of 37 degrees C.

Factor Associated with Neutral Sphingomyelinase Activity Mediates Navigational Capacity of Leukocytes Responding to Wounds and Infection: Live Imaging Studies in Zebrafish Larvae

PubMed Central

Boecke, Alexandra; Sieger, Dirk; Neacsu, Cristian Dan; Kashkar, Hamid

2012-01-01

Factor associated with neutral sphingomyelinase activity (FAN) is an adaptor protein that specifically binds to the p55 receptor for TNF (TNF-RI). Our previous investigations demonstrated that FAN plays a role in TNF-induced actin reorganization by connecting the plasma membrane with actin cytoskeleton, suggesting that FAN may impact on cellular motility in response to TNF and in the context of immune inflammatory conditions. In this study, we used the translucent zebrafish larvae for in vivo analysis of leukocyte migration after morpholino knockdown of FAN. FAN-deficient zebrafish leukocytes were impaired in their migration toward tail fin wounds, leading to a reduced number of cells reaching the wound. Furthermore, FAN-deficient leukocytes show an impaired response to bacterial infections, suggesting that FAN is generally required for the directed chemotactic response of immune cells independent of the nature of the stimulus. Cell-tracking analysis up to 3 h after injury revealed that the reduced number of leukocytes is not due to a reduction in random motility or speed of movement. Leukocytes from FAN-deficient embryos protrude pseudopodia in all directions instead of having one clear leading edge. Our results suggest that FAN-deficient leukocytes exhibit an impaired navigational capacity, leading to a disrupted chemotactic response. PMID:22802420

Correlation of interleukin-6 and monocyte chemotactic protein-1 concentrations with crescent formation and myeloperoxidase-specific anti-neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti-interleukin-6 receptor antibody or mizoribine.

PubMed

Nagao, Tomokazu; Kusunoki, Reina; Iwamura, Chiaki; Kobayashi, Shigeto; Yumura, Wako; Kameoka, Yosuke; Nakayama, Toshinori; Suzuki, Kazuo

2013-09-01

Myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN. The serum concentration of soluble IL-6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio-Plex analysis. Sections of frozen kidney tissue were examined by fluorescence microscopy and the CD3(+) B220(+) T cell subset in the spleen determined by a flow cytometry. Concentrations of IL-6 and monocyte chemotactic protein-1 were significantly correlated with the percentages of crescent formation. Anti-IL-6R antibody, which has been effective in patients with rheumatoid arthritis, was administered to SCG/Kj mice to elucidate the role of IL-6 in the development of RPGN. MPO-ANCA titers decreased after administration of anti-IL-6R antibody, but not titers of mizoribine, which is effective in Kawasaki disease model mice. These results suggest that IL-6-mediated signaling is involved in the production of MPO-ANCA. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

Investigations into the design principles in the chemotactic behavior of Escherichia coli.

PubMed

Kim, Tae-Hwan; Jung, Sung Hoon; Cho, Kwang-Hyun

2008-01-01

Inspired by the recent studies on the analysis of biased random walk behavior of Escherichia coli[Passino, K.M., 2002. Biomimicry of bacterial foraging for distributed optimization and control. IEEE Control Syst. Mag. 22 (3), 52-67; Passino, K.M., 2005. Biomimicry for Optimization, Control and Automation. Springer-Verlag, pp. 768-798; Liu, Y., Passino, K.M., 2002. Biomimicry of social foraging bacteria for distributed optimization: models, principles, and emergent behaviors. J. Optim. Theory Appl. 115 (3), 603-628], we have developed a model describing the motile behavior of E. coli by specifying some simple rules on the chemotaxis. Based on this model, we have analyzed the role of some key parameters involved in the chemotactic behavior to unravel the underlying design principles. By investigating the target tracking capability of E. coli in a maze through computer simulations, we found that E. coli clusters can be controlled as target trackers in a complex micro-scale-environment. In addition, we have explored the dynamical characteristics of this target tracking mechanism through perturbation of parameters under noisy environments. It turns out that the E. coli chemotaxis mechanism might be designed such that it is sensitive enough to efficiently track the target and also robust enough to overcome environmental noises.

3D simulations of early blood vessel formation

NASA Astrophysics Data System (ADS)

Cavalli, F.; Gamba, A.; Naldi, G.; Semplice, M.; Valdembri, D.; Serini, G.

2007-08-01

Blood vessel networks form by spontaneous aggregation of individual cells migrating toward vascularization sites (vasculogenesis). A successful theoretical model of two-dimensional experimental vasculogenesis has been recently proposed, showing the relevance of percolation concepts and of cell cross-talk (chemotactic autocrine loop) to the understanding of this self-aggregation process. Here we study the natural 3D extension of the computational model proposed earlier, which is relevant for the investigation of the genuinely three-dimensional process of vasculogenesis in vertebrate embryos. The computational model is based on a multidimensional Burgers equation coupled with a reaction diffusion equation for a chemotactic factor and a mass conservation law. The numerical approximation of the computational model is obtained by high order relaxed schemes. Space and time discretization are performed by using TVD schemes and, respectively, IMEX schemes. Due to the computational costs of realistic simulations, we have implemented the numerical algorithm on a cluster for parallel computation. Starting from initial conditions mimicking the experimentally observed ones, numerical simulations produce network-like structures qualitatively similar to those observed in the early stages of in vivo vasculogenesis. We develop the computation of critical percolative indices as a robust measure of the network geometry as a first step towards the comparison of computational and experimental data.

Elucidation of Distinct Roles of Guinea Pig CXCR1 and CXCR2 in Neutrophil Migration toward IL-8 and GROα by Specific Antibodies.

PubMed

Tanaka, Kento; Yoshitomi, Tomomi; Hirahara, Kazuki

2017-01-01

Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors. Neutrophil migration induced by IL-8 was partially inhibited by either anti-CXCR1 antibody or anti-CXCR2 antibody. In addition, the migration was inhibited completely when both anti-CXCR1 and anti-CXCR2 antibodies were combined. On the other hand, neutrophil migration induced by GROα was not inhibited by anti-CXCR1 antibody while inhibited profoundly by anti-CXCR2 antibody. These results indicated that CXCR1 and CXCR2 mediated migration induced by the IL-8 synergistically and only CXCR2 mediated migration induced by GROα in guinea pig neutrophils. Our findings on ligand selectivity of CXCR1 and CXCR2 in guinea pigs are consistent with those in humans.

Dimensionless Analysis Applied to Bacterial Chemotaxis towards NAPL Contaminants

NASA Astrophysics Data System (ADS)

Wang, X.; GAO, B.; Zhong, W.; Kihaule, K. S.; Ford, R.

2017-12-01

The use of chemotactic bacteria in bioremediation may improve the efficiency and decrease the cost of restoration, which means it has the potential to address environmental problems caused by oil spills. However, most previous studies were focused at the laboratory-scale and there lacks a formalism that can use these laboratory-scale results as input to evaluate the relative importance of chemotaxis at the field scale. In this study, a dimensionless equation is formulated to solve this problem. First, the main influential factors were extracted based on previous researches in environmental bioremediation and then five sets of dimensionless numbers were obtained according to Buckingham theory. After collecting basic parameter values and supplementary calculations to determine the concentration gradient of the chemoattractant, all dimensionless numbers were calculated and categorized into two types, those that were sensitive to chemotaxis or those to groundwater velocity. The bacteria ratio (BR), defined as the ratio of maximum bacteria concentration to its original value, was correlated with a combination of dimensionless numbers to yield, BR=cP1-0.085P20.329P30.1P4-0.098. For a bacterial ratio greater than one, the bioremediation strategy based on chemotaxis is expected to be effective, and chemotactic bacteria are expected to accumulate around NAPL contaminant sources efficiently.

Identification of an Envelope Protein from the FRD Family of Human Endogenous Retroviruses (HERV-FRD) Conferring Infectivity and Functional Conservation among Simians

PubMed Central

Blaise, Sandra; Ruggieri, Alessia; Dewannieux, Marie; Cosset, François-Loic; Heidmann, Thierry

2004-01-01

A member of the HERV-W family of human endogenous retroviruses (HERV) had previously been demonstrated to encode a functional envelope which can form pseudotypes with human immunodeficiency virus type 1 virions and confer infectivity on the resulting retrovirus particles. Here we show that a second envelope protein sorted out by a systematic search for fusogenic proteins that we made among all the HERV coding envelope genes and belonging to the HERV-FRD family can also make pseudotypes and confer infectivity. We further show that the orthologous envelope genes that were isolated from simians—from New World monkeys to humans—are also functional in the infectivity assay, with one singular exception for the gibbon HERV-FRD gene, which is found to be fusogenic in a cell-cell fusion assay, as observed for the other simian envelopes, but which is not infectious. Sequence comparison of the FRD envelopes revealed a limited number of mutations among simians, and one point mutation—located in the TM subunit—was shown to be responsible for the loss of infectivity of the gibbon envelope. The functional characterization of the identified envelopes is strongly indicative of an ancestral retrovirus infection and endogenization, with some of the envelope functions subsequently retained in evolution. PMID:14694139

Identification of an envelope protein from the FRD family of human endogenous retroviruses (HERV-FRD) conferring infectivity and functional conservation among simians.

PubMed

Blaise, Sandra; Ruggieri, Alessia; Dewannieux, Marie; Cosset, François-Loic; Heidmann, Thierry

2004-01-01

A member of the HERV-W family of human endogenous retroviruses (HERV) had previously been demonstrated to encode a functional envelope which can form pseudotypes with human immunodeficiency virus type 1 virions and confer infectivity on the resulting retrovirus particles. Here we show that a second envelope protein sorted out by a systematic search for fusogenic proteins that we made among all the HERV coding envelope genes and belonging to the HERV-FRD family can also make pseudotypes and confer infectivity. We further show that the orthologous envelope genes that were isolated from simians-from New World monkeys to humans-are also functional in the infectivity assay, with one singular exception for the gibbon HERV-FRD gene, which is found to be fusogenic in a cell-cell fusion assay, as observed for the other simian envelopes, but which is not infectious. Sequence comparison of the FRD envelopes revealed a limited number of mutations among simians, and one point mutation-located in the TM subunit-was shown to be responsible for the loss of infectivity of the gibbon envelope. The functional characterization of the identified envelopes is strongly indicative of an ancestral retrovirus infection and endogenization, with some of the envelope functions subsequently retained in evolution.

Microbial dispersal in unsaturated porous media: Characteristics of motile bacterial cell motions in unsaturated angular pore networks

NASA Astrophysics Data System (ADS)

Ebrahimi, Ali N.; Or, Dani

2014-09-01

The dispersal rates of self-propelled microorganisms affect their spatial interactions and the ecological functioning of microbial communities. Microbial dispersal rates affect risk of contamination of water resources by soil-borne pathogens, the inoculation of plant roots, or the rates of spoilage of food products. In contrast with the wealth of information on microbial dispersal in water replete systems, very little is known about their dispersal rates in unsaturated porous media. The fragmented aqueous phase occupying complex soil pore spaces suppress motility and limits dispersal ranges in unsaturated soil. The primary objective of this study was to systematically evaluate key factors that shape microbial dispersal in model unsaturated porous media to quantify effects of saturation, pore space geometry, and chemotaxis on characteristics of principles that govern motile microbial dispersion in unsaturated soil. We constructed a novel 3-D angular pore network model (PNM) to mimic aqueous pathways in soil for different hydration conditions; within the PNM, we employed an individual-based model that considers physiological and biophysical properties of motile and chemotactic bacteria. The effects of hydration conditions on first passage times in different pore networks were studied showing that fragmentation of aquatic habitats under dry conditions sharply suppresses nutrient transport and microbial dispersal rates in good agreement with limited experimental data. Chemotactically biased mean travel speed of microbial cells across 9 mm saturated PNM was ˜3 mm/h decreasing exponentially to 0.45 mm/h for the PNM at matric potential of -15 kPa (for -35 kPa, dispersal practically ceases and the mean travel time to traverse the 9 mm PNM exceeds 1 year). Results indicate that chemotaxis enhances dispersal rates by orders of magnitude relative to random (diffusive) motions. Model predictions considering microbial cell sizes relative to available liquid pathways sizes were in good agreement with experimental results for unsaturated soils. The new modeling platform enables quantitative consideration of key biophysical factors (e.g., pore space heterogeneities and hydration conditions) governing microbial interactions in 3-D soil pore spaces.

Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance

PubMed Central

Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

2015-01-01

Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis, and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intra-amniotic infection has been generally considered to be the cause of acute histologic chorioamnionitis and funisitis; however, recent evidence indicates that “sterile” intra-amniotic inflammation, which occurs in the absence of demonstrable microorganisms but can be induced by “danger signals”, is frequently associated with these lesions. In the context of intra-amniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient favoring the migration of neutrophils from maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and is present in 3-5% of placentas delivered at term, but in 94% of placentas delivered between 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks for the fetal inflammatory response syndrome, a condition characterized by an elevation in fetal plasma concentrations of interleukin-6, associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multi-organ fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

Molecular and functional characterization of tumor-induced factor (TIF): Hamster homolog of CXCL3 (GROγ) displays tumor suppressive activity.

PubMed

Jin, Lili; Li, Zhou-Fang; Wang, Da-Kui; Sun, Meina; Qi, Wei; Ma, Qiang; Zhang, Li; Chu, Chun; Chan, Elaine Y M; Lee, Susanna S T; Wise, Helen; To, Ka-Fai; Shi, Ying; Zhou, Naiming; Cheung, Wing-Tai

2018-02-01

Previously our lab has created a mouse ovarian xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis, and RNA profiling identified a putative chemokine tumor-induced factor (Tif). Sequence analysis and chemotactic study suggested that Tif was likely to be a hamster homolog of human GROγ (CXCL3) [IJC 125 (2009): 1316-1327]. In the present study, we report the molecular and functional characterization of the Tif gene. Genomic study of CHO-K1 cells indicated that Tif gene consisted of 4 exons, characterized with an antisense B1 element which is embedded in the fourth exon. Two Tif transcripts were identified which shared identical sequences except that a string of 71-nt derived from the antisense B1 element was deficient in the shorter transcript. Of interests, B1-like RNA ladder was detected in xenografts. Functional studies showed that TIF induced chemotaxis and neovessel formation. Pharmacological studies suggested that TIF activated Gi-coupled CXCR2 and induced both calcium mobilization and ERK1/2 phosphorylation, and suppressed forskolin-stimulated cAMP accumulation. In addition, secreted matured TIF functioned as an autocrine factor and promoted anchorage-independent growth. Unexpectedly, TIF delayed the onset of tumor formation, possibly via suppressing proliferation of stromal fibroblasts. However, TIF did not exert any inhibitory effect on tumor growth. Potentially, TIF could be used for preventing cancer relapse. Copyright © 2017 Elsevier Ltd. All rights reserved.

PREFACE: 13th International Conference on Metrology and Properties of Engineering Surfaces

NASA Astrophysics Data System (ADS)

Leach, Richard

2011-08-01

The 13th International Conference on Metrology and Properties of Engineering Surfaces focused on the progress in surface metrology, surface characterisation instrumentation and properties of engineering surfaces. The conference provided an international forum for academics, industrialists and engineers from different disciplines to meet and exchange their ideas, results and latest research. The conference was held at Twickenham Stadium, situated approximately six miles from Heathrow Airport and approximately three miles from the National Physical Laboratory (NPL). This was the thirteenth in the very successful series of conferences, which have firmly established surface topography as a new and exciting interdisciplinary field of scientific and technological studies. Scientific Themes: Surface, Micro and Nano Metrology Measurement and Instrumentation Metrology for MST Devices Freeform Surface Measurement and Characterisation Uncertainty, Traceability and Calibration AFM/SPM Metrology Tribology and Wear Phenomena Functional Applications Stylus and Optical Instruments

Summary of talks and papers at ISCB-Asia/SCCG 2012

PubMed Central

2013-01-01

The second ISCB-Asia conference of the International Society for Computational Biology took place December 17-19, 2012, in Shenzhen, China. The conference was co-hosted by BGI as the first Shenzhen Conference on Computational Genomics (SCCG). 45 talks were presented at ISCB-Asia/SCCG 2012. The topics covered included software tools, reproducible computing, next-generation sequencing data analysis, transcription and mRNA regulation, protein structure and function, cancer genomics and personalized medicine. Nine of the proceedings track talks are included as full papers in this supplement. In this report we first give a short overview of the conference by listing some statistics and visualizing the talk abstracts as word clouds. Then we group the talks by topic and briefly summarize each one, providing references to related publications whenever possible. Finally, we close with a few comments on the success of this conference.

Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study.

PubMed

Fenske, Wiebke K; Dubb, Sukhpreet; Bueter, Marco; Seyfried, Florian; Patel, Karishma; Tam, Frederick W K; Frankel, Andrew H; le Roux, Carel W

2013-01-01

Bariatric surgery improves arterial hypertension and renal function; however, the underlying mechanisms and effect of different surgical procedures are unknown. In the present prospective study, we compared the 12-month follow-up results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function, and inflammatory status. A total of 34 morbidly obese patients were investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10), laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve gastrectomy (n = 11) for hypertension, kidney function, urinary and serum cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic protein-1, and chemokine ligand-18. At 12 months after surgery, the patients in all 3 treatment arms showed a significant decrease in the mean body mass index, mean arterial pressure, and urinary and serum inflammatory markers (all P < .001). The reduction in urinary and serum cytokine levels correlated directly with body weight loss (P < .05). Patients with impaired renal function at baseline (corresponding to serum cystatin C >.8 mg/L) had a marked improvement in renal function 12 months after surgery (P < .05). Surgically induced weight loss is associated with a marked decrease in renal and systemic inflammation and arterial hypertension and improvement in renal function in patients with pre-existing renal impairment. These effects appear to be independent of surgical procedure. The improvement in renal inflammation could be 1 of the mechanisms contributing to the beneficial effects of bariatric surgery on arterial blood pressure, proteinuria, and renal function. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

A Conversation Analysis of the Function of Silence in Writing Conferences

ERIC Educational Resources Information Center

Mirzaee, Milad; Yaqubi, Baqer

2016-01-01

One of the recent issues in English as a Second/Foreign Language (ESL/EFL) writing instruction has been the quest for a more effective way to give feedback to L2 learners' writing drafts. Although teacher-learner writing conferences have been increasingly used for providing ample opportunity for negotiating revisions, relatively little attention…

Proceedings of the Conference on Psychology and the Process of Schooling in the Next Decade: Alternative Conceptions.

ERIC Educational Resources Information Center

Reynolds, Maynard C., Ed.

The conference intended to stimulate dialogue between psychologists and educators for the purpose of developing "creative propositions" that address the functions of schooling with the most relevant and advanced psychological knowledge. Most broadly, the papers and critiques are concerned with how psychology could be used to improve: (1)…

Are functional foods redefining nutritional requirements?

PubMed

Jones, Peter J; Varady, Krista A

2008-02-01

Functional foods are increasing in popularity owing to their ability to confer health and physiological benefits. Nevertheless, the notion that functional foods improve health when providing nutrients at levels above and beyond existing recommended intakes is inconsistent with the definition of requirement. This disparity highlights the need for an alternative definition of nutrient requirement. The present objective is to examine distinctions between optimization of health, as defined by what we currently deem as required intakes, versus adding physiological benefit using bioactive agents found in functional foods. Presently, requirement is defined as the lowest amount of intake of a nutrient that will maintain a defined level of nourishment for a specific indicator of adequacy. In contrast, functional foods are described as ingredients that are not necessary for body function, yet provide added physiological benefit that confer better overall health. Plant sterols are one example of such an ingredient. Plant sterols lower plasma cholesterol concentrations, and may thus be considered essential nutrients in physiological situations where circulating cholesterol concentrations are high. Similarly, intakes of omega-3 fats beyond existing requirement may confer additional health benefits such as hypolipidemic and anti-diabetic effects. These examples underscore the inconsistencies between what is defined as a nutrient requirement versus what is identified as a health benefit of a functional food. Such discrepancies emphasize the need for a more all-encompassing definition of a nutrient requirement; that is, one that moves beyond the prevention of overt deficiency to encompass improved health and disease risk reduction.

Biofabricated film with enzymatic and redox-capacitor functionalities to harvest and store electrons.

PubMed

Liba, Benjamin D; Kim, Eunkyoung; Martin, Alexandra N; Liu, Yi; Bentley, William E; Payne, Gregory F

2013-03-01

Exciting opportunities in bioelectronics will be facilitated by materials that can bridge the chemical logic of biology and the digital logic of electronics. Here we report the fabrication of a dual functional hydrogel film that can harvest electrons from its chemical environment and store these electrons by switching the film's redox-state. The hydrogel scaffold was formed by the anodic deposition of the aminopolysaccharide chitosan. Electron-harvesting function was conferred by co-depositing the enzyme glucose dehydrogenase (GDH) with chitosan. GDH catalyzes the transfer of electrons from glucose to the soluble redox-shuttle NADP(+). Electron-storage function was conferred by the redox-active food phenolic chlorogenic acid (CA) that was enzymatically grafted to the chitosan scaffold using tyrosinase. The grafted CA undergoes redox-cycling reactions with NADPH resulting in the net transfer of electrons to the film where they are stored in the reduced state of CA. The individual and dual functionalities of these films were demonstrated experimentally. There are three general conclusions from this proof-of-concept study. First, enzymatically-grafted catecholic moieties confer redox-capacitor function to the chitosan scaffold. Second, biological materials (i.e. chitosan and CA) and mechanisms (i.e. tyrosinase-mediated grafting) allow the reagentless fabrication of functional films that should be environmentally-friendly, safe and potentially even edible. Finally, the film's ability to mediate the transfer of electrons from a biological metabolite to an electrode suggests an approach to bridge the chemical logic of biology with the digital logic of electronics.

Proceedings ICASS 2017

NASA Astrophysics Data System (ADS)

Fu, Qiang; Schaaf, Peter

2018-07-01

This special issue of the high impact international peer reviewed journal Applied Surface Science represents the proceedings of the 2nd International Conference on Applied Surface Science ICASS held 12-16 June 2017 in Dalian China. The conference provided a forum for researchers in all areas of applied surface science to present their work. The main topics of the conference are in line with the most popular areas of research reported in Applied Surface Science. Thus, this issue includes current research on the role and use of surfaces in chemical and physical processes, related to catalysis, electrochemistry, surface engineering and functionalization, biointerfaces, semiconductors, 2D-layered materials, surface nanotechnology, energy, new/functional materials and nanotechnology. Also the various techniques and characterization methods will be discussed. Hence, scientific research on the atomic and molecular level of material properties investigated with specific surface analytical techniques and/or computational methods is essential for any further progress in these fields.

International conference on Functional Materials and Nanotechnologies (FM&NT-2013), 21-24 April 2013, Tartu, Estonia

NASA Astrophysics Data System (ADS)

Nõmmiste, Ergo; Kirm, Marco; Plank, Toomas

2014-04-01

The annual international conference Functional Materials and Nanotechnologies (FM&NT) was started in 2006 by scientists from the Institute of Solid State Physics, University of Latvia. The warm welcome and open atmosphere of this scientific conference has turned it into an event where people from different countries and different fields come and meet under the shared umbrella of functional materials and nanotechnology. It is particularly important for early stage scientists who are looking for new knowledge and contacts with people from various fields to build their own network. Our Latvian colleagues, with their success in internationalization, made us neighbouring Estonians so jealous that we could not help but propose organising the conference every second year in Estonia. In a way, this conference is a continuation of the idea of the famous Baltic seminars which took place over several decades in the last century. Due to political constraints, these seminars were only open to scientists of former Eastern Europe countries, but had a great popularity and attendance from over the whole Soviet Union. Many collaborations started from the initial personal contact between scientists at these twice yearly seminars, held alternately in Latvia and Estonia. At the FM&NT 2012 conference, the decision was made that Institute of Physics, University of Tartu would organise the next event in Tartu in 2013. FM&NT-2013 was hence held in Tartu (Estonia) from 21-24 April 2013 at the Dorpat Conference Centre. The main selected topics of the conference were: (i) multifunctional materials, (ii) nanomaterials, (iii) materials for sustainable energy applications and (vi) theory. Additionally, the focus in this conference was on studies with the help of synchrotron radiation and other novel light sources such as free electron lasers. The conference provided an opportunity for 300 scientists from 21 countries to meet, establish contacts, exchange knowledge and discuss their research. During the three days of the conference, 14 invited talks were given, 45 oral and five commercial talks by companies were delivered and more than 200 posters were presented and discussed. As an outcome of the conference, 14 contributions were selected as regular papers to be submitted as a special section in Physica Scripta , and they are published in this issue. Additionally, 62 papers submitted based on the conference contributions, were included in IOP Conference Series : Materials Science and Engineering and are available at http://iopscience.iop.org/1757-899X/49/1. Additional information about FM&NT-2013 is available at its homepage http://fmnt.ut.ee/. Future information regarding the conference will be published on the website. Photograph. Photograph. Participants of FM&NT-2013, the photo was taken in front of the Science Centre AHHAA on 23 April 2013. Acknowledgement The Organizing Committee would like to thank all the speakers, contributors, session chairs and other staff involved for their personal efforts in making FM&NT-2013 successful and memorable. We express our thanks to all the authors for their research contribution presented in this issue. We express our gratitude to all of the reviewers and editors with special thanks to the Editor-in-Chief of Physica Scripta Dr Suzy Lidström, who took part of the conference with an invited talk. The efforts of members of the IOP Publishing team, especially the publisher Yasmin McGlashan, and the guest editor from the local organizing committee Dr Rainer Pärna, are also gratefully acknowledged. We would like to acknowledge financial support by Tartu University Development Fund, Estonian national projects supporting Materials Science, Science Internationalisation and Centre of Excellence programs based on the contribution of the European Structural Funds and Estonian national funding. Also, the graduate school on 'Functional Materials and Technologies' supported by the European Social Fund has given a generous contribution to assist in the participation of our early stage researchers. This support is gratefully acknowledged. We also would like to acknowledge and thank all the sponsors, companies (Raith, Bruker, Vistec Lithography, Saint-Tech, The Doma Group, Armgate and American Elements) who create conditions for our everyday research in the Baltics. We hope that the continuation of the tradition introduced with this conference will strengthen the international cooperation of scientists from Baltic states with researchers from other countries. In particular, we very much value the communication between new generations of researches which takes place, ensuring the fruitful development of science in our countries. The Organizing Committee hopes that the conference FM&NT-2013 gave the participants good insight into recent progress in nanotechnology, sustainable energetics, the processing and modelling of multifunctional materials and research enabled by the use of synchrotron radiation or other novel light sources such as free electron lasers. We sincerely hope that the conference has provided support for the circulation of information and brought together many young and experienced scientists from different fields, leading to fruitful discussions. We hope that all of the participants had an ejoyable and memorable time in Tartu. We welcome you back in the future.

Self-help conferences for people who stutter: a qualitative investigation.

PubMed

Trichon, Mitchell; Tetnowski, John

2011-12-01

Self-help activities for people who stutter (PWS) have been gaining in popularity; however, there is a scarcity of evidence to support their utility in stuttering management. The purpose of this investigation was to understand the lived experience of individuals who attended a self-help conference(s) for PWS from the perspective of a PWS to learn its potential utility in stuttering management. The investigator used Interpretive Phenomenological Analysis (IPA) to systematically collect authentic data of this social phenomenon. Twelve participants were recruited from a self-help conference and the self-help community of PWS. Semi-structured interviews were conducted 4-18 months after each participant's last conference. Interviews were transcribed and analyzed. Themes were explained in investigator narratives and illustrated through participants' quotes. Interpreted themes of the experience of having attended a self-help conference(s) for PWS included: socializing opportunities with other PWS, affiliation, redefining oneself and post-conference disclosures. A conclusion of the study was that the experience of having attended a self-help conference(s) for PWS helped to minimize negative impact that stuttering can have on daily functioning. It appears that self-help conferences were perceived as a safer or "stutter-friendly" environment and promoted social interaction, relationship building, and community building through planned and unplanned activities. Another conclusion was that the experience of having attended self-help conferences for PWS helped participants to communicate more easily. Reported increases in social activity and an "openness" about stuttering, suggest self-help conferences' utility in stuttering management. These findings are supported by other studies about successful stuttering management and self-help activities for PWS. They have helped attendees who stutter to communicate more easily and suggest a reduction in the negative impact that stuttering has on their lives. The reader will be able to: (1) describe recurring themes associated with the lived experience having attended a self-help conference(s) for people who stutter (PWS) from the perspective of a group of adults who stutter, and (2) describe the potential benefits of attending self-help conferences for PWS in order to make appropriate evidence-based referrals to self-help conferences for PWS. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of HSP27 on Human Breast Tumor Cell Growth and Motility

DTIC Science & Technology

1999-08-01

the small stress protein, HSP27 , on growth and motility characteristics of normal and tumor-derived human mammary cell lines. We hypothesized that...cells overexpressing HSP27 would show increased motility, altered chemotactic properties, increased resistance to heat killing and to certain drugs...Donna has prepared and studied 19 clonal MDA23 1 breast tumor cell lines that overexpress human HSP27 , and determined that, while heat resistance is

Knowledge Bases for Education Policies. Proceedings of a Conference (Maastricht, The Netherlands, September 11-13, 1995).

ERIC Educational Resources Information Center

Organisation for Economic Cooperation and Development, Paris (France). Centre for Educational Research and Innovation.

The forms of knowledge that are relevant to education are diverse as well as complex. In 1995 the CERI, the Dutch Ministry of Education, Culture and Science, and the Belgium Flemish Ministry of Education held a conference in Maastricht to examine ways in which educational research-and-development systems functioned in various countries.…

Report of a Planning Conference for Solar Technology Information Transfer in Kentucky (Frankfort, September 11-12, 1978).

ERIC Educational Resources Information Center

Capps, Randall, Ed.

This summary of the deliberations of the Planning Conference for Solar Technology Information Transfer includes an outline of a functioning solar energy technology network for the State of Kentucky and a set of recommendations for future action. Four main types of information agents were identified: (1) the State Library System; (2) the State…

Report of a Planning Conference for Solar Technology Information Transfer (Nashville, Tennessee, September 28-29, 1977).

ERIC Educational Resources Information Center

Gleaves, Edwin S., Ed.

A summary of the deliberations of the Planning Conference for Solar Technology Information Transfer--to discuss and outline a functioning solar energy technology network in the State of Tennessee--and a set of recommendations for future action are presented in this report. Topic areas include: (1) the Tennessee Regional Library Service; (2) the…

Vocational Education--Priorities and Strategies. Report of the WCOTP Southern Africa Regional Conference (5th, Lilongwe and Mangochi, Malawi, September 22-26, 1985).

ERIC Educational Resources Information Center

World Confederation of Organizations of the Teaching Profession, Morges (Switzerland).

This document reports the proceedings of a conference in Southern Africa that addressed two themes: (1) priorities and strategies for the reform of vocational education; and (2) the functions of teacher organizations. The following presentations are included: "Opening Address" (Frank A. P. Mkomawanthu); "Keynote Address: Priorities…

Thematic Structure in Barack Obama's Press Conference: A Systemic Functional Grammar Study

ERIC Educational Resources Information Center

Kuswoyo, Heri

2016-01-01

This article looks into the theme--rheme pattern of presidential press conference that can be employed by speakers to organize the text in order to have a texture. Since a message should be conveyed in clause contextually and co-textually. Therefore, the objectives of this study are to analyze and describe the theme-rheme pattern employed in…

International Psychological Applications Conference and Trends (InPACT) Proceedings (Porto, Portugal, April 4-6, 2014)

ERIC Educational Resources Information Center

Pracana, Clara, Ed.

2014-01-01

We are delighted to welcome you to the International Psychological Applications Conference and Trends 2014, taking place in Porto, Portugal, from 4 to 6 of April. Psychology, in our time, offers a large range of scientific fields where it can be applied. The goal of understanding individuals and groups (mental functions and behavioral…

International Psychological Applications Conference and Trends (InPACT) 2016 (Lisbon, Portugal, April 30-May 2, 2016)

ERIC Educational Resources Information Center

Pracana, Clara, Ed.; Wang, Michael, Ed.

2016-01-01

We are delighted to welcome you to the International Psychological Applications Conference and Trends (InPACT) 2016, taking place in Lisbon, Portugal, from 30 of April to 2 of May, 2016. Psychology, nowadays, offers a large range of scientific fields where it can be applied. The goal of understanding individuals and groups (mental functions and…

International Psychological Applications Conference and Trends (InPACT) Proceedings (Ljubljana, Slovenia, May 2-4, 2015)

ERIC Educational Resources Information Center

Pracana, Clara, Ed.

2015-01-01

We are delighted to welcome you to the International Psychological Applications Conference and Trends (InPACT) 2015, taking place in Ljubljana, Slovenia, from 2 to 4 of May. Psychology, nowadays, offers a large range of scientific fields where it can be applied. The goal of understanding individuals and groups (mental functions and behavioral…

Functioning Mathematically: 1

ERIC Educational Resources Information Center

Cain, David

2007-01-01

This article presents the first part of the closing address given by the author to the 2007 Association of Teachers of Mathematics (ATM) Easter conference at Loughborough. In his closing address, the author focuses on functioning mathematically as opposed to functional mathematics. His view of functional mathematics is that the focus is on someone…

75 FR 43797 - Delegation of Certain Functions Under Section 1264 of the Victims of Iranian Censorship Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... Certain Functions Under Section 1264 of the Victims of Iranian Censorship Act (Public Law 111-84, Subtitle... State, the functions conferred upon the President by section 1264 of the Victims of Iranian Censorship...

Antigen-Specific Induction of Osteopontin Contributes to the Chronification of Allergic Contact Dermatitis

PubMed Central

Seier, Anne M.; Renkl, Andreas C.; Schulz, Guido; Uebele, Tanja; Sindrilaru, Anca; Iben, Sebastian; Liaw, Lucy; Kon, Shigeyuki; Uede, Toshimitsu; Weiss, Johannes M.

2010-01-01

Allergic contact dermatitis is a T cell-mediated immune response, which in its relapsing chronic form is of high socioeconomic impact. The phosphoglycoprotein osteopontin (OPN) has chemotactic and Th1 cytokine functions and in various models is essential for robust T cell-mediated immunity. Here we demonstrate that OPN is abundantly expressed by both effector T cells and keratinocytes in allergic contact dermatitis lesions. T cells from nickel-allergic donors secrete high levels of OPN following antigen-specific stimulation. OPN may substitute for missing IFN-γ secretion in T effector cells because low IFN-γ-producing T cell clones secrete high levels of OPN, and OPN down-modulates their interleukin-4 expression. Furthermore, interferon-γ from T effector cells augments OPN in allergic contact dermatitis by inducing OPN in keratinocytes, which in turn polarizes dendritic cells and attracts inflammatory cells. In the murine contact hypersensitivity (CHS) model for allergic contact dermatitis, OPN is strongly induced in antigen-specific proliferating T cells, and OPN null mice display a reduced chronic CHS inflammatory response due to a decreased influx of effector T cells. Importantly, because of its function for chronic allergic contact dermatitis, OPN may well be a therapeutic target, because anti-OPN antibody treatment in part suppresses established chronic CHS. PMID:20008129

Analyzing inflammatory response as excitable media

NASA Astrophysics Data System (ADS)

Yde, Pernille; Høgh Jensen, Mogens; Trusina, Ala

2011-11-01

The regulatory system of the transcription factor NF-κB plays a great role in many cell functions, including inflammatory response. Interestingly, the NF-κB system is known to up-regulate production of its own triggering signal—namely, inflammatory cytokines such as TNF, IL-1, and IL-6. In this paper we investigate a previously presented model of the NF-κB, which includes both spatial effects and the positive feedback from cytokines. The model exhibits the properties of an excitable medium and has the ability to propagate waves of high cytokine concentration. These waves represent an optimal way of sending an inflammatory signal through the tissue as they create a chemotactic signal able to recruit neutrophils to the site of infection. The simple model displays three qualitatively different states; low stimuli leads to no or very little response. Intermediate stimuli leads to reoccurring waves of high cytokine concentration. Finally, high stimuli leads to a sustained high cytokine concentration, a scenario which is toxic for the tissue cells and corresponds to chronic inflammation. Due to the few variables of the simple model, we are able to perform a phase-space analysis leading to a detailed understanding of the functional form of the model and its limitations. The spatial effects of the model contribute to the robustness of the cytokine wave formation and propagation.

PAI1 mediates fibroblast-mast cell interactions in skin fibrosis.

PubMed

Pincha, Neha; Hajam, Edries Yousaf; Badarinath, Krithika; Batta, Surya Prakash Rao; Masudi, Tafheem; Dey, Rakesh; Andreasen, Peter; Kawakami, Toshiaki; Samuel, Rekha; George, Renu; Danda, Debashish; Jacob, Paul Mazhuvanchary; Jamora, Colin

2018-05-01

Fibrosis is a prevalent pathological condition arising from the chronic activation of fibroblasts. This activation results from the extensive intercellular crosstalk mediated by both soluble factors and direct cell-cell connections. Prominent among these are the interactions of fibroblasts with immune cells, in which the fibroblast-mast cell connection, although acknowledged, is relatively unexplored. We have used a Tg mouse model of skin fibrosis, based on expression of the transcription factor Snail in the epidermis, to probe the mechanisms regulating mast cell activity and the contribution of these cells to this pathology. We have discovered that Snail-expressing keratinocytes secrete plasminogen activator inhibitor type 1 (PAI1), which functions as a chemotactic factor to increase mast cell infiltration into the skin. Moreover, we have determined that PAI1 upregulates intercellular adhesion molecule type 1 (ICAM1) expression on dermal fibroblasts, rendering them competent to bind to mast cells. This heterotypic cell-cell adhesion, also observed in the skin fibrotic disorder scleroderma, culminates in the reciprocal activation of both mast cells and fibroblasts, leading to the cascade of events that promote fibrogenesis. Thus, we have identified roles for PAI1 in the multifactorial program of fibrogenesis that expand its functional repertoire beyond its canonical role in plasmin-dependent processes.

15. international conference on plant growth substances: Program -- Abstracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Since the 14th Conference in Amsterdam in 1991, progress in plant hormone research and developmental plant biology has been truly astonishing. The five ``classical`` plant hormones, auxin, gibberellin, cytokinin, ethylene, and abscisic acid, have been joined by a number of new signal molecules, e.g., systemin, jasmonic acid, salicylic acid, whose biosynthesis and functions are being understood in ever greater detail. Molecular genetics has opened new vistas in an understanding of transduction pathways that regulate developmental processes in response to hormonal and environmental signals. The program of the 15th Conference includes accounts of this progress and brings together scientists whose workmore » focuses on physiological, biochemical, and chemical aspects of plant growth regulation. This volume contains the abstracts of papers presented at this conference.« less

An Arabidopsis Soil-Salinity–Tolerance Mutation Confers Ethylene-Mediated Enhancement of Sodium/Potassium Homeostasis[W

PubMed Central

Jiang, Caifu; Belfield, Eric J.; Cao, Yi; Smith, J. Andrew C.; Harberd, Nicholas P.

2013-01-01

High soil Na concentrations damage plants by increasing cellular Na accumulation and K loss. Excess soil Na stimulates ethylene-induced soil-salinity tolerance, the mechanism of which we here define via characterization of an Arabidopsis thaliana mutant displaying transpiration-dependent soil-salinity tolerance. This phenotype is conferred by a loss-of-function allele of ETHYLENE OVERPRODUCER1 (ETO1; mutant alleles of which cause increased production of ethylene). We show that lack of ETO1 function confers soil-salinity tolerance through improved shoot Na/K homeostasis, effected via the ETHYLENE RESISTANT1–CONSTITUTIVE TRIPLE RESPONSE1 ethylene signaling pathway. Under transpiring conditions, lack of ETO1 function reduces root Na influx and both stelar and xylem sap Na concentrations, thereby restricting root-to-shoot delivery of Na. These effects are associated with increased accumulation of RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF)–dependent reactive oxygen species in the root stele. Additionally, lack of ETO1 function leads to significant enhancement of tissue K status by an RBOHF-independent mechanism associated with elevated HIGH-AFFINITY K+ TRANSPORTER5 transcript levels. We conclude that ethylene promotes soil-salinity tolerance via improved Na/K homeostasis mediated by RBOHF-dependent regulation of Na accumulation and RBOHF-independent regulation of K accumulation. PMID:24064768

The Properties of 3 Different Plasma Formulations and Their Effects on Tendinopathic Cells.

PubMed

Rubio-Azpeitia, Eva; Bilbao, Ane M; Sánchez, Pello; Delgado, Diego; Andia, Isabel

2016-08-01

Tendinopathies are attributed to failure of the healing process and inadequate tissue remodeling. Plasma injections can trigger regenerative responses by modifying the molecular microenvironment. To examine the differences in the mitotic, chemotactic, anabolic, and inflammatory effects between leukocyte- and platelet-rich plasma (L-PRP), platelet-rich plasma (PRP), and platelet-poor plasma (PPP). Controlled laboratory study. Tendinopathic cells were cultured in 3-dimensional (3D) hydrogels formed using PPP, PRP, and L-PRP. Cell migration was evaluated using a μ-Slide chemotaxis chamber with video microscopy. Proliferation was assessed using XTT assays. Expression of genes associated with matrix turnover, including type 1 collagen (COL1A1), COL3A1, aggrecan, decorin, fibronectin, matrix metalloproteinase 1 (MMP-1), MMP-3, A Disintegrin-Like And Metalloprotease With Thrombospondin Type 1 Motif proteins 4 (ADAMTS-4), and ADAMTS-5, was assessed using real-time reverse-transcription polymerase chain reaction. Secreted inflammatory proteins, including interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein 1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES), as well as vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), were quantified using enzyme-linked immunosorbent assay. Tendinopathic cells migrate at a higher velocity along L-PRP and PRP than along PPP gradients. PRP and L-PRP promote hypercellularity. PPP and PRP showed more pronounced anabolic properties, as demonstrated by enhanced COL1A1 and COL3A1 and reduced MMP-1 expression. Decorin, fibronectin, and aggrecan were downregulated in L-PRP compared with PPP and PRP. L-PRP and PRP were shown to be more proinflammatory than PPP in terms of IL-6 secretion, but cells in PPP showed MCP-1(high) phenotype. CTGF secretion was significantly reduced in L-PRP compared with PPP and PRP. The main advantages of L-PRP and PRP use, compared with PPP, include their stronger chemotactic and proliferative properties. While PPP and PRP stimulate matrix anabolism, L-PRP is more proinflammatory. Emphasis should be placed on the temporal needs and biological characteristics of injured tendons, and plasma formulations need to be tailored accordingly. Versatile systems allowing the preparation of different plasma formulations, such as PPP, PRP, or L-PRP, can help refine clinical applications by taking advantage of their different biological properties. © 2016 The Author(s).

Rapid and Reversible Tubulin Tyrosination in Human Neutrophils Stimulated by the Chemotacted Peptide, fMet Leu-Phe

DTIC Science & Technology

1993-01-01

Ji -Il i H’a ti .. 1 populations oftnaicrotuhbules: ’Ixrosinated dnd iaontirosijnatcdalphlah RothNaivlLs %V , lia~ W.A ,and Mali pli I) li 1 ýil) I I...t11707-Il t720 , dele ateIhaut sec ra’tarv granoarie’ mavi a-� -aagaal l a lang iaaii ri ’i- Malawasta, S. 11971 1 Vinblastine: colchicine’iike eff’cts

Chemokines, their receptors, and transplant outcome.

PubMed

Colvin, Bridget L; Thomson, Angus W

2002-07-27

Organ transplant rejection is mediated largely by circulating peripheral leukocytes induced to infiltrate the graft by various inflammatory stimuli. Of these, chemotactic cytokines called chemokines, expressed by inflamed graft tissues, as well as by early innate-responding leukocytes that infiltrate the graft, are responsible for the recruitment of alloreactive leukocytes. This report discusses the impact of these leukocyte-directing proteins on transplant outcome and novel therapeutic approaches for antirejection therapy based on targeting of chemokines and/or their receptors.

Effect of HSP27 on Human Breast Tumor Cell Growth and Motility.

DTIC Science & Technology

1997-09-01

the small heat shock protein, Hsp27 , on growth and motility characteristics of human mammary tumor cell lines. Since Hsp27 regulates actin...microfilament dynamics, we hypothesize that cells expressing high levels of Hsp27 will show increased motility and altered chemotactic properties, in addition to...significantly elevated levels of Hsp27 has proven to be daunting. Down regulation of Hsp27 levels in MCF7 cells using antisense technology has also

Special Section on InterPACK 2017—Part 1

DOE PAGES

Mysore, Kaushik; Narumanchi, Sreekant; Dede, Ercan; ...

2018-03-02

InterPACK is a premier international forum for exchange of state-of-the-art knowledge in research, development, manufacturing, and applications of micro-electronics packaging. It is the flagship conference of the ASME Electronic and Photonic Packaging Division (EPPD) founded in 1992 as an ASME-JSME joint biannual conference. Rapid changes in the semiconductor landscape together with findings from InterPACK Pathfinding workshop (IPW) in 2016 led to a significant reset of InterPACK conference priorities and focus to comprehensively address needs of the InterPACK community. As a result, starting in 2017, InterPACK has become an annual conference and the scope of the conference has increased significantly togethermore » with a systems-focus to include some of the most cutting-edge topics in electronics packaging, device integration, and reliability. These topics are organized across five different tracks: (1) heterogeneous integration: microsystems with diverse functionality, (2) servers of the future, (3) structural and physical health monitoring, (4) energy conversion and storage, and (5) transportation: autonomous and electric vehicles.« less

Special Section on InterPACK 2017—Part 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mysore, Kaushik; Narumanchi, Sreekant; Dede, Ercan

InterPACK is a premier international forum for exchange of state-of-the-art knowledge in research, development, manufacturing, and applications of micro-electronics packaging. It is the flagship conference of the ASME Electronic and Photonic Packaging Division (EPPD) founded in 1992 as an ASME-JSME joint biannual conference. Rapid changes in the semiconductor landscape together with findings from InterPACK Pathfinding workshop (IPW) in 2016 led to a significant reset of InterPACK conference priorities and focus to comprehensively address needs of the InterPACK community. As a result, starting in 2017, InterPACK has become an annual conference and the scope of the conference has increased significantly togethermore » with a systems-focus to include some of the most cutting-edge topics in electronics packaging, device integration, and reliability. These topics are organized across five different tracks: (1) heterogeneous integration: microsystems with diverse functionality, (2) servers of the future, (3) structural and physical health monitoring, (4) energy conversion and storage, and (5) transportation: autonomous and electric vehicles.« less

Guest Editorial: Special Section on InterPACK 2017 - Part 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narumanchi, Sreekant V; Mysore, Kaushik; Dede, Ercan

InterPACK is a premier international forum for exchange of state-of-the-art knowledge in research, development, manufacturing, and applications of micro-electronics packaging. It is the flagship conference of the ASME Electronic and Photonic Packaging Division (EPPD) founded in 1992 as an ASME-JSME joint biannual conference. Rapid changes in the semiconductor landscape together with findings from InterPACK Pathfinding workshop (IPW) in 2016 led to a significant reset of InterPACK conference priorities and focus to comprehensively address needs of the InterPACK community. As a result, starting in 2017, InterPACK has become an annual conference and the scope of the conference has increased significantly togethermore » with a systems-focus to include some of the most cutting-edge topics in electronics packaging, device integration, and reliability. These topics are organized across five different tracks: (1) heterogeneous integration: microsystems with diverse functionality, (2) servers of the future, (3) structural and physical health monitoring, (4) energy conversion and storage, and (5) transportation: autonomous and electric vehicles.« less

Monocyte chemotactic protein-3: possible involvement in apical periodontitis chemotaxis.

PubMed

Dezerega, A; Osorio, C; Mardones, J; Mundi, V; Dutzan, N; Franco, M; Gamonal, J; Oyarzún, A; Overall, C M; Hernández, M

2010-10-01

To study the expression of monocyte chemotactic protein-3 (MCP-3, also known as chemokine CCL-7) in tissue from apical lesions (AL) and to associate MCP-3 expression with symptomatic or asymptomatic apical periodontitis. To determine the expression of MCP-3 in AL, biopsies obtained during tooth extraction procedures were fixed, subjected to routine processing and diagnosed as apical granuloma (AG) (n = 7) or radicular cyst (RC) (n = 5). As controls, apical periodontal ligament (PDL) specimens from healthy premolars extracted for orthodontics reasons were included (n = 7). All specimens were immunostained for MCP-3 and examined under a light microscope. In addition, homogenates from AL (n = 14) and healthy PDL samples (n = 7) were studied through immunowestern blot. Finally, periapical exudates samples were collected from root canals of teeth having diagnosis of symptomatic (n = 14) and asymptomatic apical periodontitis (n = 14) during routine endodontic treatments and analysed by immunowestern blot and densitometry.   MCP-3 was detected in AG and RC and localized mainly to inflammatory leucocytes, whereas no expression was observed in healthy PDLs. MCP-3 was also detected in periapical exudate, and its levels were significantly higher in symptomatic than in asymptomatic apical periodontitis. MCP-3 was expressed in AL and its levels associated with clinical symptoms. MCP-3 might play a role in disease pathogenesis, possibly by stimulating mononuclear chemotaxis. © 2010 International Endodontic Journal.

Study of Chemotaxis and Cell–Cell Interactions in Cancer with Microfluidic Devices

PubMed Central

Sai, Jiqing; Rogers, Matthew; Hockemeyer, Kathryn; Wikswo, John P.; Richmond, Ann

2017-01-01

Microfluidic devices have very broad applications in biological assays from simple chemotaxis assays to much more complicated 3D bioreactors. In this chapter, we describe the design and methods for performing chemotaxis assays using simple microfluidic chemotaxis chambers. With these devices, using real-time video microscopy we can examine the chemotactic responses of neutrophil-like cells under conditions of varying gradient steepness or flow rate and then utilize software programs to calculate the speed and angles of cell migration as gradient steepness and flow are varied. Considering the shearing force generated on the cells by the constant flow that is required to produce and maintain a stable gradient, the trajectories of the cell migration will reflect the net result of both shear force generated by flow and the chemotactic force resulting from the chemokine gradient. Moreover, the effects of mutations in chemokine receptors or the presence of inhibitors of intracellular signals required for gradient sensing can be evaluated in real time. We also describe a method to monitor intracellular signals required for cells to alter cell polarity in response to an abrupt switch in gradient direction. Lastly, we demonstrate an in vitro method for studying the interactions of human cancer cells with human endothelial cells, fibroblasts, and leukocytes, as well as environmental chemokines and cytokines, using 3D microbioreactors that mimic the in vivo microenvironment. PMID:26921940

Analysis of bacterial migration. 2: Studies with multiple attractant gradients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strauss, I.; Frymier, P.D.; Hahn, C.M.

1995-02-01

Many motile bacteria exhibit chemotaxis, the ability to bias their random motion toward or away from increasing concentrations of chemical substances which benefit or inhibit their survival, respectively. Since bacteria encounter numerous chemical concentration gradients simultaneously in natural surroundings, it is necessary to know quantitatively how a bacterial population responds in the presence of more than one chemical stimulus to develop predictive mathematical models describing bacterial migration in natural systems. This work evaluates three hypothetical models describing the integration of chemical signals from multiple stimuli: high sensitivity, maximum signal, and simple additivity. An expression for the tumbling probability for individualmore » stimuli is modified according to the proposed models and incorporated into the cell balance equation for a 1-D attractant gradient. Random motility and chemotactic sensitivity coefficients, required input parameters for the model, are measured for single stimulus responses. Theoretical predictions with the three signal integration models are compared to the net chemotactic response of Escherichia coli to co- and antidirectional gradients of D-fucose and [alpha]-methylaspartate in the stopped-flow diffusion chamber assay. Results eliminate the high-sensitivity model and favor the simple additivity over the maximum signal. None of the simple models, however, accurately predict the observed behavior, suggesting a more complex model with more steps in the signal processing mechanism is required to predict responses to multiple stimuli.« less

The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?

PubMed

Yoshimura, Teizo

2018-01-29

Macrophages are one of the most abundant leukocyte populations infiltrating tumor tissues and can exhibit both tumoricidal and tumor-promoting activities. In 1989, we reported the purification of monocyte chemoattractant protein-1 (MCP-1) from culture supernatants of mitogen-activated peripheral blood mononuclear cells and tumor cells. MCP-1 is a potent monocyte-attracting chemokine, identical to the previously described lymphocyte-derived chemotactic factor or tumor-derived chemotactic factor, and greatly contributes to the recruitment of blood monocytes into sites of inflammatory responses and tumors. Because in vitro-cultured tumor cells often produce significant amounts of MCP-1, tumor cells are considered to be the main source of MCP-1. However, various non-tumor cells in the tumor stroma also produce MCP-1 in response to stimuli. Studies performed in vitro and in vivo have provided evidence that MCP-1 production in tumors is a consequence of complex interactions between tumor cells and non-tumor cells and that both tumor cells and non-tumor cells contribute to the production of MCP-1. Although MCP-1 production was once considered to be a part of host defense against tumors, it is now believed to regulate the vicious cycle between tumor cells and macrophages that promotes the progression of tumors.Cellular and Molecular Immunology advance online publication, 29 January 2018; doi:10.1038/cmi.2017.135.

Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression.

PubMed

Blich, Miry; Golan, Amnon; Arvatz, Gil; Sebbag, Anat; Shafat, Itay; Sabo, Edmond; Cohen-Kaplan, Victoria; Petcherski, Sirouch; Avniel-Polak, Shani; Eitan, Amnon; Hammerman, Haim; Aronson, Doron; Axelman, Elena; Ilan, Neta; Nussbaum, Gabriel; Vlodavsky, Israel

2013-02-01

Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. Highly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls. Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.

Cellular cAMP uptake as trigger for electrotaxis

NASA Astrophysics Data System (ADS)

Guido, Isabella; Bodenschatz, Eberhard

Cells have the ability to detect continuous current electric fields and respond to them with a directed migratory movement. Dictyostelium discoideum cells, a key model organism for the study of eukaryotic chemotaxis, orient and migrate toward the cathode under the influence of an electric field. The underlying sensing mechanism and whether it is shared by the chemotactic response pathway remains unknown. By investigating the migration in the electric field of cell strains unable to migrate chemotactically (Amib-null) and with defective cAMP relay (ACA-null) we show that the starvation-induced transcription of a set of genes involved in the early developmental stage is not necessary for electrotaxis. However, the analysis of electrotaxis of vegetative cells as well as shortly starved cells shows that cells need to be stimulated with cAMP in order for them to migrate electrotactically. Indeed 30 minutes stimulation with cAMP pulses is enough to let cells orienting with the electric field although during this time the expression of receptors and the beginning of the development has not happened yet. We believe that the reason for this observed phenomenon lies on the endocytosis of the external cAMP which triggers electrotaxis as long as endocytosis and exocytosis are not balanced. This work is part of the MaxSynBio Consortium which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society.

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

NASA Astrophysics Data System (ADS)

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.

Induction of the chemotactic S100 protein, CP-10, in monocyte/macrophages by lipopolysaccharide.

PubMed

Hu, S P; Harrison, C; Xu, K; Cornish, C J; Geczy, C L

1996-05-01

The murine S100 protein CP-10 is a potent chemotactic factor for murine and human myeloid cells in vivo and in vitro. This is the first report describing regulations of the CP-10 gene by a proinflammatory stimulus, lipopolysaccharide (LPS), in cells of the monocyte/macrophage lineage. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells preexposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. This was accompanied by increasing levels of cell-associated and released CP-10 protein. In contrast, a single dose of LPS upregulated CP-10 mRNA in elicited peritoneal macrophages, whereas mRNA and protein levels decreased following LPS challenge. The state of macrophage differentiation may control responsiveness as LPS had no effect on CP-10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expression was controlled at the transcriptional level and nuclear run-on and protein synthesis inhibition assays indicated that LPS priming and challenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not induced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gram-negative bacterial infection.

Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci.

PubMed

Hanson, D F; Murphy, P A; Windle, B E

1980-06-01

Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophages. When mononuclear cells were added back to purified neutrophils, no pyrogen was produced that could not be accounted for by the number of macrophages added. Rabbit blood cells were similarly fractionated on colloidal silica gradients. Again, endogenous pyrogen was made only by the adherent mononuclear population. The neutrophils isolated on these gradients appeared to be morphologically normal and were 85% viable as judged by dye exclusion. They showed normal random motility. Both blood and exudate neutrophils responded chemotactically to N-formyl Met-Leu-Phe, and blood neutrophils responded chemotactically to zymosan-activated serum. Both kinds of neutrophils phagocytosed zymosan particles and both killed opsonized S. epidermidis in a roller tube system. Both blood and exudate neutrophils showed normal superoxide production when stimulated with opsonized zymosan particles. This evidence suggests that macrophages are the only source of endogenous pyrogens, and that pyrogens secreted by cell populations that are rich in neutrophils are to be attributed to the monocytes or macrophages that they contain.

Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci

PubMed Central

1980-01-01

Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophages. When mononuclear cells were added back to purified neutrophils, no pyrogen was produced that could not be accounted for by the number of macrophages added. Rabbit blood cells were similarly fractionated on colloidal silica gradients. Again, endogenous pyrogen was made only by the adherent mononuclear population. The neutrophils isolated on these gradients appeared to be morphologically normal and were 85% viable as judged by dye exclusion. They showed normal random motility. Both blood and exudate neutrophils responded chemotactically to N-formyl Met-Leu-Phe, and blood neutrophils responded chemotactically to zymosan-activated serum. Both kinds of neutrophils phagocytosed zymosan particles and both killed opsonized S. epidermidis in a roller tube system. Both blood and exudate neutrophils showed normal superoxide production when stimulated with opsonized zymosan particles. This evidence suggests that macrophages are the only source of endogenous pyrogens, and that pyrogens secreted by cell populations that are rich in neutrophils are to be attributed to the monocytes or macrophages that they contain. PMID:6247413

Branching instability in expanding bacterial colonies.

PubMed

Giverso, Chiara; Verani, Marco; Ciarletta, Pasquale

2015-03-06

Self-organization in developing living organisms relies on the capability of cells to duplicate and perform a collective motion inside the surrounding environment. Chemical and mechanical interactions coordinate such a cooperative behaviour, driving the dynamical evolution of the macroscopic system. In this work, we perform an analytical and computational analysis to study pattern formation during the spreading of an initially circular bacterial colony on a Petri dish. The continuous mathematical model addresses the growth and the chemotactic migration of the living monolayer, together with the diffusion and consumption of nutrients in the agar. The governing equations contain four dimensionless parameters, accounting for the interplay among the chemotactic response, the bacteria-substrate interaction and the experimental geometry. The spreading colony is found to be always linearly unstable to perturbations of the interface, whereas branching instability arises in finite-element numerical simulations. The typical length scales of such fingers, which align in the radial direction and later undergo further branching, are controlled by the size parameters of the problem, whereas the emergence of branching is favoured if the diffusion is dominant on the chemotaxis. The model is able to predict the experimental morphologies, confirming that compact (resp. branched) patterns arise for fast (resp. slow) expanding colonies. Such results, while providing new insights into pattern selection in bacterial colonies, may finally have important applications for designing controlled patterns. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.

PubMed

Jantan, Ibrahim; Harun, Nurul Hikmah; Septama, Abdi Wira; Murad, Shahnaz; Mesaik, M A

2011-04-01

The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 μg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 μg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 μg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.

Analysis of migration rate and chemotaxis of human adipose-derived mesenchymal stem cells in response to LPS and LTA in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herzmann, Nicole; Salamon, Achim; Fiedler, Tomas

Mesenchymal stem cells (MSC) are able to stimulate the regeneration of injured tissue. Since bacterial infections are common complications in wound healing, bacterial pathogens and their components come into direct contact with MSC. The interaction with bacterial structures influences the proliferation, differentiation and migratory activity of the MSC, which might be of relevance during regeneration. Studies on MSC migration in response to bacterial components have shown different results depending on the cell type. Here, we analyzed the migration rate and chemotaxis of human adipose-derived MSC (adMSC) in response to the basic cell-wall components lipopolysaccharide (LPS) of Gram-negative bacteria and lipoteichoicmore » acid (LTA) of Gram-positive bacteria in vitro. To this end, we used transwell and scratch assays, as well as a specific chemotaxis assay combined with live-cell imaging. We found no significant influence of LPS or LTA on the migration rate of adMSC in transwell or scratch assays. Furthermore, in the µ-slide chemotaxis assay, the stimulation with LPS did not exert any chemotactic effect on adMSC. - Highlights: • LPS increased the release of IL-6 and IL-8 in adMSC significantly. • The migration rate of adMSC was not influenced by LPS or LTA. • LPS or LTA did not exert a chemotactic effect on adMSC.« less

Chemotaxis-mediated biodegradation of cyclic nitramine explosives RDX, HMX, and CL-20 by Clostridium sp. EDB2.

PubMed

Bhushan, Bharat; Halasz, Annamaria; Thiboutot, Sonia; Ampleman, Guy; Hawari, Jalal

2004-04-09

Cyclic nitramine explosives, RDX, HMX, and CL-20 are hydrophobic pollutants with very little aqueous solubility. In sediment and soil environments, they are often attached to solid surfaces and/or trapped in pores and distribute heterogeneously in aqueous environments. For efficient bioremediation of these explosives, the microorganism(s) must access them by chemotaxis ability. In the present study, we isolated an obligate anaerobic bacterium Clostridium sp. strain EDB2 from a marine sediment. Strain EDB2, motile with numerous peritrichous flagella, demonstrated chemotactic response towards RDX, HMX, CL-20, and NO(2)(-). The three explosives were biotransformed by strain EDB2 via N-denitration with concomitant release of NO(2)(-). Biotransformation rates of RDX, HMX, and CL-20 by the resting cells of strain EDB2 were 1.8+/-0.2, 1.1+/-0.1, and 2.6+/-0.2nmol h(-1)mgwet biomass(-1) (mean+/-SD; n=3), respectively. We found that commonly seen RDX metabolites such as TNX, methylenedinitramine, and 4-nitro-2,4-diazabutanal neither produced NO(2)(-) during reaction with strain EDB2 nor they elicited chemotaxis response in strain EDB2. The above data suggested that NO(2)(-) released from explosives during their biotransformation might have elicited chemotaxis response in the bacterium. Biodegradation and chemotactic ability of strain EDB2 renders it useful in accelerating the bioremediation of explosives under in situ conditions.

Analytical modeling and experimental characterization of chemotaxis in Serratia marcescens

NASA Astrophysics Data System (ADS)

Zhuang, Jiang; Wei, Guopeng; Wright Carlsen, Rika; Edwards, Matthew R.; Marculescu, Radu; Bogdan, Paul; Sitti, Metin

2014-05-01

This paper presents a modeling and experimental framework to characterize the chemotaxis of Serratia marcescens (S. marcescens) relying on two-dimensional and three-dimensional tracking of individual bacteria. Previous studies mainly characterized bacterial chemotaxis based on population density analysis. Instead, this study focuses on single-cell tracking and measuring the chemotactic drift velocity VC from the biased tumble rate of individual bacteria on exposure to a concentration gradient of l-aspartate. The chemotactic response of S. marcescens is quantified over a range of concentration gradients (10-3 to 5 mM/mm) and average concentrations (0.5×10-3 to 2.5 mM). Through the analysis of a large number of bacterial swimming trajectories, the tumble rate is found to have a significant bias with respect to the swimming direction. We also verify the relative gradient sensing mechanism in the chemotaxis of S. marcescens by measuring the change of VC with the average concentration and the gradient. The applied full pathway model with fitted parameters matches the experimental data. Finally, we show that our measurements based on individual bacteria lead to the determination of the motility coefficient μ (7.25×10-6 cm2/s) of a population. The experimental characterization and simulation results for the chemotaxis of this bacterial species contribute towards using S. marcescens in chemically controlled biohybrid systems.

Diagnostic and Therapeutic Radiopharmaceutical Agents for Selective Discrimination of Prostate Cancer

DTIC Science & Technology

2009-10-01

Bottenus, Brienne N.∞; Fugate, Glenn A.†; Benny, Paul*. Actinides Separations, Conference Pacific Northwest National Lab 6/2006 In situ formation of...Bottenus, Brienne N.∞; Benny, Paul*. Actinides Separations, Conference Pacific Northwest National Lab 3/12/2006 S-functionalized cysteine ligands...cancer imaging. The successful preparation and radiolabeling of the first generation of compounds illustrates one the key critical objectives being

Cross border waters: Fragile treasures for the 21st Century; Ninth U.S./Mexico Border States Conference on Recreation, Parks, and Wildlife; 1998, June 3-6

Treesearch

G. J. Gottfried; C. B. Edminster; Madelyn C. Dillon

1998-01-01

This conference brought together scientists and resource managers from government, universities, and private organizations in the United States and Mexico. In a continuing international forum, participants exchanged information on existing or potential cooperative projects, agency functions and programs, and issues were concerning natural and cultural resource...

Proceedings of the Conference of the International Group for the Psychology of Mathematics Education (PME) (24th, Hiroshima, Japan, July 23-27, 2000), Volume 3.

ERIC Educational Resources Information Center

Nakahara, Tadao, Ed.; Koyama, Masataka, Ed.

The third volume of the 24th annual conference of the International Group for the Psychology of Mathematics Education contains full research report papers. Papers include: (1) "Mathematics classrooms functioning as communities of inquiry: Possibilities and constraints for changing practice" (Susie Groves, Brian Doig, and Laurance Splitter); (2)…

SELECTED PAPERS FROM PROFESSIONAL PROGRAM SEGMENTS OF UNITED CEREBRAL PALSY'S ANNUAL CONFERENCE (15TH, LOS ANGELES, CALIFORNIA, MARCH 11-13, 1965).

ERIC Educational Resources Information Center

United Cerebral Palsy Association, New York, NY.

THIS PUBLICATION PRESENTS SELECTED PAPERS FROM THE UNITED CEREBRAL PALSY ASSOCIATION'S 15TH ANNUAL CONFERENCE, MARCH 13, 1965. PAPERS ARE--(1) "S IS TO TURN" BY PAUL V. CARLSON, (2) "CERTAIN ASPECTS OF THE FUNCTIONAL STATUS OF THE FETUS IN UTERO" BY FORREST H. ADAMS, (3) "ENCEPHALITIS--COMMON CAUSES AND AFTER EFFECTS"…

Transactions of the Army Conference on Applied Mathematics and Computing (6th) Held in Boulder, Colorado on 31 May - 3 June 1988

DTIC Science & Technology

1989-02-01

North American algebraists, in academic mathematics departments, appear to have computer anxiety or computation anxiety . Conferences and...the Heaviside function of S[4,51. H(S)[(p+ Vov] =0 (1) D H(S)[ HRv + Vp = 0 (2) Dt where D 8 a -- = +3- (3) We nondimensionalize the equations by using

Solar Technology Information Transfer in South Carolina: Report of a Planning Conference (Columbia, South Carolina, August 1-2, 1978).

ERIC Educational Resources Information Center

Gissendanner, Cassandra S., Ed.

The deliberations of the planning conference to discuss and outline a statewide functioning solar energy technology network and a set of recommendations for future action are presented in this report. Topic areas include background information on both the project and the current energy information system in South Carolina, along with a summary of…

A Bioinformatic Approach to Inter Functional Interactions within Protein Sequences

DTIC Science & Technology

2009-02-23

AFOSR/AOARD Reference Number: USAFAOGA07: FA4869-07-1-4050 AFOSR/AOARD Program Manager : Hiroshi Motoda, Ph.D. Period of...Conference on Knowledge Discovery and Data Mining.) In a separate study we have applied our approaches to the problem of whole genome alignment. We have...SIGKDD Conference on Knowledge Discovery and Data Mining Attached. Interactions: Please list: (a) Participation/presentations at meetings

1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1999-02-12

This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conferencemore » sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.« less

A DBMS-based medical teleconferencing system.

PubMed

Chun, J; Kim, H; Lee, S; Choi, J; Cho, H

2001-01-01

This article presents the design of a medical teleconferencing system that is integrated with a multimedia patient database and incorporates easy-to-use tools and functions to effectively support collaborative work between physicians in remote locations. The design provides a virtual workspace that allows physicians to collectively view various kinds of patient data. By integrating the teleconferencing function into this workspace, physicians are able to conduct conferences using the same interface and have real-time access to the database during conference sessions. The authors have implemented a prototype based on this design. The prototype uses a high-speed network test bed and a manually created substitute for the integrated patient database.

A DBMS-based Medical Teleconferencing System

PubMed Central

Chun, Jonghoon; Kim, Hanjoon; Lee, Sang-goo; Choi, Jinwook; Cho, Hanik

2001-01-01

This article presents the design of a medical teleconferencing system that is integrated with a multimedia patient database and incorporates easy-to-use tools and functions to effectively support collaborative work between physicians in remote locations. The design provides a virtual workspace that allows physicians to collectively view various kinds of patient data. By integrating the teleconferencing function into this workspace, physicians are able to conduct conferences using the same interface and have real-time access to the database during conference sessions. The authors have implemented a prototype based on this design. The prototype uses a high-speed network test bed and a manually created substitute for the integrated patient database. PMID:11522766

Interfamily Transfer of Dual NB-LRR Genes Confers Resistance to Multiple Pathogens

PubMed Central

Narusaka, Mari; Kubo, Yasuyuki; Hatakeyama, Katsunori; Imamura, Jun; Ezura, Hiroshi; Nanasato, Yoshihiko; Tabei, Yutaka; Takano, Yoshitaka; Shirasu, Ken; Narusaka, Yoshihiro

2013-01-01

A major class of disease resistance (R) genes which encode nucleotide binding and leucine rich repeat (NB-LRR) proteins have been used in traditional breeding programs for crop protection. However, it has been difficult to functionally transfer NB-LRR-type R genes in taxonomically distinct families. Here we demonstrate that a pair of Arabidopsis (Brassicaceae) NB-LRR-type R genes, RPS4 and RRS1, properly function in two other Brassicaceae, Brassica rapa and Brassica napus, but also in two Solanaceae, Nicotiana benthamiana and tomato (Solanum lycopersicum). The solanaceous plants transformed with RPS4/RRS1 confer bacterial effector-specific immunity responses. Furthermore, RPS4 and RRS1, which confer resistance to a fungal pathogen Colletotrichum higginsianum in Brassicaceae, also protect against Colletotrichum orbiculare in cucumber (Cucurbitaceae). Importantly, RPS4/RRS1 transgenic plants show no autoimmune phenotypes, indicating that the NB-LRR proteins are tightly regulated. The successful transfer of two R genes at the family level implies that the downstream components of R genes are highly conserved. The functional interfamily transfer of R genes can be a powerful strategy for providing resistance to a broad range of pathogens. PMID:23437080

Boundedness for a 3D chemotaxis-Stokes system with porous medium diffusion and tensor-valued chemotactic sensitivity

NASA Astrophysics Data System (ADS)

Wang, Yilong; Li, Xie

2017-04-01

This paper deals with the following chemotaxis-Stokes system n_t+u\\cdot nabla n=Δ n^m-nabla \\cdot (nS(x,n,c)\\cdot nabla c), &{}quad xin Ω , t>0, c_t+u\\cdot nabla c=Δ c-nf(c),&{}quad xin Ω , t>0, u_t=Δ u+nabla P+nnabla φ ,&quad xin Ω , t>0,\\ nabla \\cdot u=0,&{}quad xin Ω , t>0. under no-flux boundary conditions in a bounded domain Ω subset R3 with smooth boundary, where m≥ 1, φ in W^{1,∞}(Ω ), f and S are given functions with values in [0, ∞) and R^{3× 3}, respectively. Here S satisfies |S(x,n,c)|7/6, which insures the global existence of bounded weak solution. Our result covers completely and improves the recent result by Wang and Cao (Discrete Contin Dyn Syst Ser B 20:3235-3254, 2015) which asserts, just in the case m=1, the global existence of solutions, but without boundedness, and that by Winkler (Calc Var Partial Differ Equ 54:3789-3828, 2015) which only involves the case of α =0 and requires the convexity of the domain.

iAMP-2L: a two-level multi-label classifier for identifying antimicrobial peptides and their functional types.

PubMed

Xiao, Xuan; Wang, Pu; Lin, Wei-Zhong; Jia, Jian-Hua; Chou, Kuo-Chen

2013-05-15

Antimicrobial peptides (AMPs), also called host defense peptides, are an evolutionarily conserved component of the innate immune response and are found among all classes of life. According to their special functions, AMPs are generally classified into ten categories: Antibacterial Peptides, Anticancer/tumor Peptides, Antifungal Peptides, Anti-HIV Peptides, Antiviral Peptides, Antiparasital Peptides, Anti-protist Peptides, AMPs with Chemotactic Activity, Insecticidal Peptides, and Spermicidal Peptides. Given a query peptide, how can we identify whether it is an AMP or non-AMP? If it is, can we identify which functional type or types it belong to? Particularly, how can we deal with the multi-type problem since an AMP may belong to two or more functional types? To address these problems, which are obviously very important to both basic research and drug development, a multi-label classifier was developed based on the pseudo amino acid composition (PseAAC) and fuzzy K-nearest neighbor (FKNN) algorithm, where the components of PseAAC were featured by incorporating five physicochemical properties. The novel classifier is called iAMP-2L, where "2L" means that it is a 2-level predictor. The 1st-level is to answer the 1st question above, while the 2nd-level is to answer the 2nd and 3rd questions that are beyond the reach of any existing methods in this area. For the conveniences of users, a user-friendly web-server for iAMP-2L was established at http://www.jci-bioinfo.cn/iAMP-2L. Copyright © 2013 Elsevier Inc. All rights reserved.

Dopamine, T cells and multiple sclerosis (MS).

PubMed

Levite, Mia; Marino, Franca; Cosentino, Marco

2017-05-01

Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in EAE-afflicted animals. In a single clinical trial, MS patients did not benefit from bromocriptine, which is a D2-like DR agonist. Nevertheless, multiple evidence showing dopaminergic abnormalities in T cells in MS encourages testing other DR analogues/drugs in MS, possibly as "add-on" to IFN-β or other MS-immunomodulating therapies. Together, abnormalities in DRs in T cells can contribute to MS, and DRs in T cells can be therapeutic targets in MS. Finally and in a more general scope: the direct effects of all dopaminergic drugs on human T cells should be studied in further depth, and also taken into consideration whenever treating patients with any disease, to avoid detrimental side effects on the immune system of the patients.

Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic Nematodes Strongyloides ratti and Trichuris suis Affects Mucosal Homeostasis

PubMed Central

Hansmann, Jan; Winter, Dominic; Schramm, Guido; Erttmann, Klaus D.; Liebau, Eva

2016-01-01

The cellular redox state is important for the regulation of multiple functions and is essential for the maintenance of cellular homeostasis and antioxidant defense. In the excretory/secretory (E/S) products of Strongyloides ratti and Trichuris suis sequences for thioredoxin (Trx) and Trx-like protein (Trx-lp) were identified. To characterize the antioxidant Trx-lp and its interaction with the parasite's mucosal habitat, S. ratti and T. suis Trx-lps were cloned and recombinantly expressed. The primary antioxidative activity was assured by reduction of insulin and IgM. Further analysis applying an in vitro mucosal 3D-cell culture model revealed that the secreted Trx-lps were able to bind to monocytic and intestinal epithelial cells and induce the time-dependent release of cytokines such as TNF-α, IL-22, and TSLP. In addition, the redox proteins also possessed chemotactic activity for monocytic THP-1 cells and fostered epithelial wound healing activity. These results confirm that the parasite-secreted Trx-lps are multifunctional proteins that can affect the host intestinal mucosa. PMID:27872753

Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt signaling pathway and an inflammatory response in adipose tissue.

PubMed

Sun, Ruixin; Wu, Yi; Hou, Weihua; Sun, Zujun; Wang, Yuxiong; Wei, Huanhuan; Mo, Wei; Yu, Min

2017-01-01

Insulin resistance is a major metabolic abnormality in a large majority of patients with type II diabetes. Bromodomain-containing protein 2 (Brd2), a transcriptional co-activator/co-repressor with switch mating type/sucrose non-fermenting (SWI/SNF)-like functions that regulates chromatin, suppresses adipocyte differentiation and regulates pancreatic β-cell biology. However, the effects of Brd2 on insulin resistance remain unknown. Here, overexpression of Brd2 in white adipose tissue of wild-type (WT) mice led to insulin resistance. Brd2 overexpression induced the expression of nuclear Factor-κΒ (NF-κΒ) target genes, mainly involving proinflammatory and chemotactic factors, in adipocytes. Furthermore, it decreased the expression of DEP domain containing mTOR-interacting protein (Deptor) to enhance mechanistic target of rapamycin (mTOR) signaling, thus blocking insulin signaling. Collectively, these results provided evidence for a novel role of Brd2 in chronic inflammation and insulin resistance, suggesting its potential in improving insulin resistance and treating metabolic disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Adenylyl cyclase A mRNA localized at the back of cells is actively translated in live chemotaxing Dictyostelium.

PubMed

Wang, Weiye; Chen, Song; Das, Satarupa; Losert, Wolfgang; Parent, Carole A

2018-05-04

Dictyostelium discoideum cells transport adenylyl cyclase A (ACA)-containing vesicles to the back of polarized cells to relay exogenous cAMP signals during chemotaxis. Fluorescence in situ hybridization (FISH) experiments showed that ACA mRNA is also asymmetrically distributed at the back of polarized cells. By using the MS2 bacteriophage system, we now visualize the distribution of ACA mRNA in live chemotaxing cells. We found that the ACA mRNA localization is not dependent on the translation of the protein product and requires multiple cis-acting elements within the ACA-coding sequence. We show that ACA mRNA is associated with actively translating ribosomes and is transported along microtubules towards the back of cells. By monitoring the recovery of ACA-YFP after photobleaching, we observed that local translation of ACA-YFP occurs at the back of cells. These data represent a novel functional role for localized translation in the relay of chemotactic signals during chemotaxis. © 2018. Published by The Company of Biologists Ltd.

Understanding Physiological and Degenerative Natural Vision Mechanisms to Define Contrast and Contour Operators

PubMed Central

Demongeot, Jacques; Fouquet, Yannick; Tayyab, Muhammad; Vuillerme, Nicolas

2009-01-01

Background Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring. Methodology First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring. Conclusions We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery. PMID:19547712

The physical and functional thermal sensitivity of bacterial chemoreceptors.

PubMed

Frank, Vered; Koler, Moriah; Furst, Smadar; Vaknin, Ady

2011-08-19

The bacterium Escherichia coli exhibits chemotactic behavior at temperatures ranging from approximately 20 °C to at least 42 °C. This behavior is controlled by clusters of transmembrane chemoreceptors made from trimers of dimers that are linked together by cross-binding to cytoplasmic components. By detecting fluorescence energy transfer between various components of this system, we studied the underlying molecular behavior of these receptors in vivo and throughout their operating temperature range. We reveal a sharp modulation in the conformation of unclustered and clustered receptor trimers and, consequently, in kinase activity output. These modulations occurred at a characteristic temperature that depended on clustering and were lower for receptors at lower adaptational states. However, in the presence of dynamic adaptation, the response of kinase activity to a stimulus was sustained up to 45 °C, but sensitivity notably decreased. Thus, this molecular system exhibits a clear thermal sensitivity that emerges at the level of receptor trimers, but both receptor clustering and adaptation support the overall robust operation of the system at elevated temperatures. Copyright © 2011 Elsevier Ltd. All rights reserved.

2009 MICROBIAL POPULATION BIOLOGY GORDON RESEARCH CONFERENCES JULY 19-24,2009

DOE Office of Scientific and Technical Information (OSTI.GOV)

ANTHONY DEAN

2009-07-24

The 2009 Gordon Conference on Microbial Population Biology will cover a diverse range of cutting edge issues in the microbial sciences and beyond. Firmly founded in evolutionary biology and with a strongly integrative approach, past Conferences have covered a range of topics from the dynamics and genetics of adaptation to the evolution of mutation rate, community ecology, evolutionary genomics, altruism, and epidemiology. The 2009 Conference is no exception, and will include sessions on the evolution of infectious diseases, social evolution, the evolution of symbioses, experimental evolution, adaptive landscapes, community dynamics, and the evolution of protein structure and function. While genomicmore » approaches continue to make inroads, broadening our knowledge and encompassing new questions, the conference will also emphasize the use of experimental approaches to test hypotheses decisively. As in the past, this Conference provides young scientists and graduate students opportunities to present their work in poster format and exchange ideas with leading investigators from a broad spectrum of disciplines. This meeting is never dull: some of the most significant and contentious issues in biology have been thrashed out here. The 2009 meeting will be no exception.« less

In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function.

PubMed

Gorr, Matthew W; Youtz, Dane J; Eichenseer, Clayton M; Smith, Korbin E; Nelin, Timothy D; Cormet-Boyaka, Estelle; Wold, Loren E

2015-07-01

Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure. Copyright © 2015 the American Physiological Society.

Differential Contributions of Olfactory Receptor Neurons in a Drosophila Olfactory Circuit

PubMed Central

Newquist, Gunnar; Novenschi, Alexandra; Kohler, Donovan

2016-01-01

Abstract The ability of an animal to detect, discriminate, and respond to odors depends on the functions of its olfactory receptor neurons (ORNs). The extent to which each ORN, upon activation, contributes to chemotaxis is not well understood. We hypothesized that strong activation of each ORN elicits a different behavioral response in the Drosophila melanogaster larva by differentially affecting the composition of its navigational behavior. To test this hypothesis, we exposed Drosophila larvae to specific odorants to analyze the effect of individual ORN activity on chemotaxis. We used two different behavioral paradigms to analyze the chemotaxis response of larvae to odorants. When tested with five different odorants that elicit strong physiological responses from single ORNs, larval behavioral responses toward each odorant differed in the strength of attraction as well as in the composition of discrete navigational elements, such as runs and turns. Further, behavioral responses to odorants did not correlate with either the strength of odor gradients tested or the sensitivity of each ORN to its cognate odorant. Finally, we provide evidence that wild-type larvae with all ORNs intact exhibit higher behavioral variance than mutant larvae that have only a single pair of functional ORNs. We conclude that individual ORNs contribute differently to the olfactory circuit that instructs chemotactic responses. Our results, along with recent studies from other groups, suggest that ORNs are functionally nonequivalent units. These results have implications for understanding peripheral odor coding. PMID:27570823

The CXCL16 A181V mutation selectively inhibits monocyte adhesion to CXCR6 but is not associated with human coronary heart disease.

PubMed

Petit, Sarah J; Wise, Emma L; Chambers, John C; Sehmi, Jobanpreet; Chayen, Naomi E; Kooner, Jaspal S; Pease, James E

2011-04-01

The chemokine CXCL16 serves as a scavenger receptor for oxidized low-density lipoprotein and as an adhesion molecule and chemoattractant for cells expressing the receptor CXCR6. A commonly occurring CXCL16 allele has been described containing 2 nonsynonymous single-nucleotide polymorphisms in complete linkage disequilibrium, although the effects on CXCL16 function are unknown. Here, we examined the effect of the single-nucleotide polymorphisms on CXCL16 function and assessed the association of the mutant allele with coronary heart disease (CHD). Both wild-type and mutant T123V181-CXCL16 were readily expressed in vitro and were similarly functional in assays of oxidized low-density lipoprotein scavenging and chemotaxis. However, unlike wild-type CXCL16, T123V181-CXCL16 was unable to promote adhesion of CXCR6(+) cells. Findings were confirmed ex vivo, with monocytes from donors homozygous for the T123V181 allele unable to facilitate adhesion of CXCR6 transfectants. In the London Life Sciences Prospective Population cohort (n = 2797), we found that the T123V181 allele was not associated with protection or susceptibility to CHD (adjusted odds ratio, 1.01; 95% CI, 0.95 to 1.10; P = 0.74). CXCL16-mediated cell adhesion plays at best a modest role in CHD, and the scavenging and chemotactic properties of the chemokine are more likely to be more important in disease pathogenesis.

Jungle Honey Enhances Immune Function and Antitumor Activity

PubMed Central

Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C.; Sawai, Masaharu; Pinkerton, Kent E.; Takeuchi, Minoru

2011-01-01

Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261. PMID:19141489

Effect of diazepam and clonazepam on the function of isolated rat platelet and neutrophil.

PubMed

Rajtar, Grazyna; Zółkowska, Dorota; Kleinrok, Zdzisław

2002-04-01

Benzodiazepine binding sites distinct from the GABA-receptor-chloride-complex in the central nervous system have been recognized in many peripheral tissues, but their physiological role remains unexplained. Our study was undertaken to examine the effects of diazepam, clonazepam, and PK 11195, a peripheral benzodiazepine receptor antagonist, on the functional and biochemical responses of platelets and neutrophils stimulated by different physiological agonists. The experiments were conducted on isolated washed rat platelets activated by arachidonic acid (AA), adenosine 5'-diphosphate (ADP), or thrombin and on isolated rat neutrophils activated by a chemotactic peptide, formyl methionyl leucyl phenylalanine (fMLP). The results showed that neither diazepam nor clonazepam nor PK 11195 alone augmented the response of resting platelets or modified neutrophil response, but diazepam and clonazepam in a concentration-dependent manner inhibited thrombin, ADP or AA-stimulated platelet aggregation and the thrombin-induced increase in free intracellular Ca2+. Both drugs also exerted an inhibitory effect on reactive oxygen species (ROS) produced by fMLP-stimulated neutrophils. However, diazepam was about 10 times more effective than clonazepam. PK11195 did not influence platelet and neutrophil function stimulated by agonists, but reversed the inhibitory action of both benzodiazepines on platelet activation and ROS production. The results indicated that in vitro diazepam, and in a much smaller degree clonazepam, may down-regulate platelet activation and release of some proinflammatory mediators by stimulated neutrophils. These effects are probably exerted by a specific benzodiazepine binding sites.

Managing the HRD Function. Symposium 32. [AHRD Conference, 2001].

ERIC Educational Resources Information Center

2001

This document contains three papers on managing the human resource development (HRD) function. "The Relationship between Factors Impacted by the Current Economic Crisis and Human Resource Development Roles and Functions in Thailand" (Chiraprapha Tan Akaraborworn, Gary N. McLean) presents data indicating that the current economic crisis…

Proceedings of the Conference of the International Group for the Psychology of Mathematics Education (PME) (24th, Hiroshima, Japan, July 23-27, 2000), Volume 4.

ERIC Educational Resources Information Center

Nakahara, Tadao, Ed.; Koyama, Masataka, Ed.

The fourth volume of the 24th annual conference of the International Group for the Psychology of Mathematics Education contains full research report papers. Papers include: (1) "What are essential to apply the 'discovery' function of proof in lower secondary school mathematics?" (Mikio Miyazaki); (2) "The anatomy of an 'open' mathematics lesson"…

Culture and Chronic Illness: Raising Children with Disabling Conditions in a Culturally Diverse World. Papers presented at an Invitational Conference (Racine, Wisconsin, June 1992).

ERIC Educational Resources Information Center

Pediatrics, 1993

1993-01-01

This special supplement presents two background papers, three working papers, and key recommendations from a conference on culture and chronic illness in childhood. The meeting had as its goal the identification of the state of knowledge on the interface among culture, chronic illness, child development, and family functioning, for the purpose of…

Real-time fMRI neurofeedback: Progress and challenges

PubMed Central

Sulzer, J.; Haller, S.; Scharnowski, F.; Weiskopf, N.; Birbaumer, N.; Blefari, M.L.; Bruehl, A.B.; Cohen, L.G.; deCharms, R.C.; Gassert, R.; Goebel, R.; Herwig, U.; LaConte, S.; Linden, D.; Luft, A.; Seifritz, E.; Sitaram, R.

2016-01-01

In February of 2012, the first international conference on real time functional magnetic resonance imaging (rtfMRI) neurofeedback was held at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland. This review summarizes progress in the field, introduces current debates, elucidates open questions, and offers viewpoints derived from the conference. The review offers perspectives on study design, scientific and clinical applications, rtfMRI learning mechanisms and future outlook. PMID:23541800

The Education Service: In or Out of Local Government? Proceedings of the Annual Conference of the British Educational Administration Society (6th, University of Birmingham, England, September 23-24, 1977).

ERIC Educational Resources Information Center

Lambert, Kenneth, Ed.

This conference focused on the present position of British education within local government and whether schools can function effectively under local control. Issues discussed included the question of whether the schools were providing industry with employees having appropriate academic ability and social skills, the question of whether…

Curriculum Programs in Action, Their Administration and Evaluation; Report of a Conference Devoted to Description, Demonstration, and Evaluative Discussions of Innovative Programs in Vocational-Technical Education.

ERIC Educational Resources Information Center

San Francisco State Coll., CA. Center for Technological Education.

The presentation, review and evaluation of innovative vocational-technical curriculums in operation was the major function of a San Francisco conference sponsored jointly by the Center for Technical Education at San Francisco State College and the Center for Studies in Vocational and Technical Education at the University of Wisconsin. Major…

Loss of function of a rice TPR-domain RNA-binding protein confers broad-spectrum disease resistance.

PubMed

Zhou, Xiaogang; Liao, Haicheng; Chern, Mawsheng; Yin, Junjie; Chen, Yufei; Wang, Jianping; Zhu, Xiaobo; Chen, Zhixiong; Yuan, Can; Zhao, Wen; Wang, Jing; Li, Weitao; He, Min; Ma, Bingtian; Wang, Jichun; Qin, Peng; Chen, Weilan; Wang, Yuping; Liu, Jiali; Qian, Yangwen; Wang, Wenming; Wu, Xianjun; Li, Ping; Zhu, Lihuang; Li, Shigui; Ronald, Pamela C; Chen, Xuewei

2018-03-20

Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, only a few crop broad-spectrum resistance loci have been reported. Here, we report the identification and characterization of the rice bsr-k1 (broad-spectrum resistance Kitaake-1) mutant, which confers broad-spectrum resistance against Magnaporthe oryzae and Xanthomonas oryzae pv oryzae with no major penalty on key agronomic traits. Map-based cloning reveals that Bsr-k1 encodes a tetratricopeptide repeats (TPRs)-containing protein, which binds to mRNAs of multiple OsPAL ( OsPAL1-7 ) genes and promotes their turnover. Loss of function of the Bsr-k1 gene leads to accumulation of OsPAL1-7 mRNAs in the bsr-k1 mutant. Furthermore, overexpression of OsPAL1 in wild-type rice TP309 confers resistance to M. oryzae , supporting the role of OsPAL1 Our discovery of the bsr-k1 allele constitutes a significant conceptual advancement and provides a valuable tool for breeding broad-spectrum resistant rice. Copyright © 2018 the Author(s). Published by PNAS.

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

PubMed Central

Groves, Angela M.; Gow, Andrew J.; Massa, Christopher B.; Laskin, Jeffrey D.

2012-01-01

Surfactant protein–D (Sftpd) is a pulmonary collectin important in down-regulating macrophage inflammatory responses. In these experiments, we analyzed the effects of chronic macrophage inflammation attributable to loss of Sftpd on the persistence of ozone-induced injury, macrophage activation, and altered functioning in the lung. Wild-type (Sftpd+/+) and Sftpd−/− mice (aged 8 wk) were exposed to air or ozone (0.8 parts per million, 3 h). Bronchoalveolar lavage (BAL) fluid and tissue were collected 72 hours later. In Sftpd−/− mice, but not Sftpd+/+ mice, increased BAL protein and nitrogen oxides were observed after ozone inhalation, indicating prolonged lung injury and oxidative stress. Increased numbers of macrophages were also present in BAL fluid and in histologic sections from Sftpd−/− mice. These cells were enlarged and foamy, suggesting that they were activated. This conclusion was supported by findings of increased BAL chemotactic activity, and increased expression of inducible nitric oxide synthase in lung macrophages. In both Sftpd+/+ and Sftpd−/− mice, inhalation of ozone was associated with functional alterations in the lung. Although these alterations were limited to central airway mechanics in Sftpd+/+ mice, both central airway and parenchymal mechanics were modified by ozone exposure in Sftpd−/− mice. The most notable changes were evident in resistance and elastance spectra and baseline lung function, and in lung responsiveness to changes in positive end-expiratory pressure. These data demonstrate that a loss of Sftpd is associated with prolonged lung injury, oxidative stress, and macrophage accumulation and activation in response to ozone, and with more extensive functional changes consistent with the loss of parenchymal integrity. PMID:22878412

In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion.

PubMed

Llewellyn-Jones, C G; Johnson, M M; Mitchell, J L; Pye, A; Okafor, V C; Hill, S L; Stockley, R A

1995-09-01

Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.

75 FR 43535 - NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... problems with long-term lung health, brain development, and brain function. Nitric oxide is a chemical... and brain development and function. Since its approval, researchers have examined expanding the use of...

Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

PubMed Central

Kemp, A S; Brown, S

1980-01-01

The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

Identification and validation of vesicant therapeutic targets using a high, throughput siRNA screening approach

DTIC Science & Technology

2014-12-24

toxlet.2011.04.007 Rogers JV, Choi YW, Kiser RC et al (2004) Microarray analysis of gene expression in murine skin exposed to sulfur mustard. J Bio...Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard. Inflam- mation 21(2...Project ID Number CBM.CUTOC.04.10. RC 00114. ABSTRACT See reprint. 15. SUBJECT TERMS sulfur mustard, cutaneous injury, siRNA, high-throughput screening

Communicating prognosis with parents of critically ill infants: direct observation of clinician behaviors.

PubMed

Boss, R D; Lemmon, M E; Arnold, R M; Donohue, P K

2017-11-01

Delivering prognostic information to families requires clinicians to forecast an infant's illness course and future. We lack robust empirical data about how prognosis is shared and how that affects clinician-family concordance regarding infant outcomes. Prospective audiorecording of neonatal intensive care unit family conferences, immediately followed by parent/clinician surveys. Existing qualitative analysis frameworks were applied. We analyzed 19 conferences. Most prognostic discussion targeted predicted infant functional needs, for example, medications or feeding. There was little discussion of how infant prognosis would affect infant/family quality of life. Prognostic framing was typically optimistic. Most parents left the conference believing their infant's prognosis to be more optimistic than did clinicians. Clinician approach to prognostic disclosure in these audiotaped family conferences tended to be broad and optimistic, without detail regarding implications of infant health for infant/family quality of life. Families and clinicians left these conversations with little consensus about infant prognosis.

2009 Epigenetics Gordon Research Conference (August 9 - 14, 2009)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeanie Lee

Epigenetics refers to the study of heritable changes in genome function that occur without a change in primary DNA sequence. The 2009 Gordon Conference in Epigenetics will feature discussion of various epigenetic phenomena, emerging understanding of their underlying mechanisms, and the growing appreciation that human, animal, and plant health all depend on proper epigenetic control. Special emphasis will be placed on genome-environment interactions particularly as they relate to human disease. Towards improving knowledge of molecular mechanisms, the conference will feature international leaders studying the roles of higher order chromatin structure, noncoding RNA, repeat elements, nuclear organization, and morphogenic evolution. Traditionalmore » and new model organisms are selected from plants, fungi, and metazoans.« less